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500 more steps a day tied to 14% lower CVD risk in older adults
Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.
“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.
The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.
The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.
Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.
Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.
Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.
The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).
In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).
Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.
However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.
Small steps may get patients started
Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.
“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.
“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.
More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”
Study fills research gap for older adults
“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.
“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.
“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.
Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.
The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.
Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.
“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.
The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.
The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.
Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.
Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.
Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.
The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).
In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).
Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.
However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.
Small steps may get patients started
Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.
“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.
“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.
More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”
Study fills research gap for older adults
“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.
“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.
“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.
Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.
The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.
Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.
“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.
The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.
The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.
Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.
Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.
Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.
The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).
In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).
Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.
However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.
Small steps may get patients started
Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.
“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.
“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.
More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”
Study fills research gap for older adults
“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.
“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.
“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.
Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.
The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.
FROM EPI/LIFESTYLE 2023
U.S. vs. French guidelines for osteoporosis treatment
Lille, France – Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.
Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?
Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.
Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.
Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.
In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].
Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.
Q. But it’s not really as simple as prescribing a bisphosphonate, is it?
A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.
These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.
Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?
A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.
Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?
A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.
The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.
The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.
But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.
Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).
Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.
Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.
In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.
Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.
Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?
A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.
Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.
Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.
A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.
Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.
In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.
In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.
For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.
Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?
A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.
In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.
But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.
In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.
This article was translated from Medscape’s French edition.
A version of this article first appeared on Medscape.com.
Lille, France – Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.
Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?
Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.
Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.
Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.
In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].
Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.
Q. But it’s not really as simple as prescribing a bisphosphonate, is it?
A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.
These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.
Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?
A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.
Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?
A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.
The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.
The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.
But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.
Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).
Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.
Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.
In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.
Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.
Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?
A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.
Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.
Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.
A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.
Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.
In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.
In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.
For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.
Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?
A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.
In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.
But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.
In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.
This article was translated from Medscape’s French edition.
A version of this article first appeared on Medscape.com.
Lille, France – Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.
Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?
Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.
Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.
Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.
In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].
Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.
Q. But it’s not really as simple as prescribing a bisphosphonate, is it?
A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.
These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.
Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?
A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.
Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?
A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.
The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.
The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.
But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.
Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).
Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.
Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.
In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.
Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.
Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?
A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.
Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.
Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.
A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.
Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.
In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.
In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.
For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.
Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?
A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.
In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.
But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.
In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.
This article was translated from Medscape’s French edition.
A version of this article first appeared on Medscape.com.
Back pain: Red flags and when to image
This transcript has been edited for clarity.
Matthew F. Watto, MD: Welcome back to The Curbsiders. On tonight’s episode, we are going to be talking about back pain. I’ll use one of my famous teaching techniques: If the patient has any kind of back pain, they should just not move. Right?
Paul N. Williams, MD: That’s right, Matt – we should recommend bedrest until they get better for anyone who has any back pain? No. For back pain, early activity and exercise are great. Patients are often concerned that physical therapy will make their pain worse, so they don’t exercise. This misunderstanding is not surprising. They believe that if they are experiencing pain, it’s facilitating more damage, which is not necessarily the case. It will get better, and a little bit of anticipatory guidance goes a long way in terms of managing patient expectations related to early mobilization, early exercise, and physical therapy.
Dr. Watto: Absolutely. One of the goals of treatment is symptom relief to the extent that we’re able to achieve. We’re not expecting the pain to go to zero. That just doesn’t happen, especially if someone’s on a medication long term. Another goal is return to function. We want them sleeping. We want them to be able to tolerate movement.
We have medications – NSAIDs and muscle relaxants, which are actually tranquilizers. But most therapy for back pain doesn’t involve medications. It involves active movement, so we have to find movement that the patient enjoys doing. Passive treatments, things being done to patients, just don’t work as well.
Dr. Williams: We should be clear – we’re talking primarily about chronic back pain here. For acute back pain, we actually have some decent medications, but acute back pain tends to improve no matter what you do. We don’t have much to offer pharmacologically for chronic low back pain. The best modalities usually involve physical activity of some kind.
Dr. Watto: Let’s discuss the evaluation of back pain. Something that always comes up: Should we order imaging, and is there a right time to get it? Dr. Baraki was very clear about when to do imaging. Two big buckets of patients might need imaging.
First, a patient who has a serious underlying condition and you’re using imaging to try to diagnose it; or in a chronic setting, a patient who needs surgery, and imaging is part of the presurgical evaluation. We talked about red flags.
The red flags are major trauma, where we have reason to believe there might be something going on – if we strongly suspect infection, or the patient is injecting drugs. If the patient has a history of cancer, we would be worried that they might have a recurrence. Those are some of the main red flags. With a patient who has osteoporosis or is on chronic steroids, you might even be able to get by with plain films instead of an MRI to look for fracture.
The other thing I wanted to ask you about is, when should we get imaging? Are there any pitfalls we need to worry about?
Dr. Williams: I always like podcasts I’m not on because I enjoy listening to them much more. Dr. Baraki talked about the very specific language that is used in radiology reports, such as spondylitis, spondylolysis, and multilevel degenerative disease. They sound bad, but if they are just reframed as age-related degenerative changes, that sounds so much more benign. When discussing with patients, we should avoid medical jargon and say that we saw some changes that we would expect for someone of your age. That sounds so much better than saying we saw multilevel degenerative disease, which sounds like an alarming pathology if you’re not a physician. Without being inaccurate, we should frame the discussion such that we aren’t providing a very specific diagnosis, because that is rarely the case with chronic low back pain. Typically, many things are going on and you may never identify a single unifying diagnosis, which doesn’t tend to help anyway.
Dr. Watto: There’s evidence showing that if the radiology report uses clinical terminology that both clinician and patient think of as less serious, they are less likely to proceed to more invasive treatments. Calling an episode of back pain a “lumbar strain” helps the patient understand that this is a pretty common thing. Almost everyone is going to have an episode of back pain at some point in their life, and almost all of them will get better. Most of the time there’s no serious underlying condition.
This was a great discussion with Dr. Baraki. Click on Back Pain Update with Dr Austin Baraki to hear the full discussion. Until next time, I’ve been Dr. Matthew Frank Watto.
Dr. Williams: And I’m Dr. Paul Nelson Williams.
Dr. Watto is Clinical Assistant Professor, Department of Medicine, University of Pennsylvania, Philadelphia. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, Temple University, Philadelphia. Neither reported any conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Matthew F. Watto, MD: Welcome back to The Curbsiders. On tonight’s episode, we are going to be talking about back pain. I’ll use one of my famous teaching techniques: If the patient has any kind of back pain, they should just not move. Right?
Paul N. Williams, MD: That’s right, Matt – we should recommend bedrest until they get better for anyone who has any back pain? No. For back pain, early activity and exercise are great. Patients are often concerned that physical therapy will make their pain worse, so they don’t exercise. This misunderstanding is not surprising. They believe that if they are experiencing pain, it’s facilitating more damage, which is not necessarily the case. It will get better, and a little bit of anticipatory guidance goes a long way in terms of managing patient expectations related to early mobilization, early exercise, and physical therapy.
Dr. Watto: Absolutely. One of the goals of treatment is symptom relief to the extent that we’re able to achieve. We’re not expecting the pain to go to zero. That just doesn’t happen, especially if someone’s on a medication long term. Another goal is return to function. We want them sleeping. We want them to be able to tolerate movement.
We have medications – NSAIDs and muscle relaxants, which are actually tranquilizers. But most therapy for back pain doesn’t involve medications. It involves active movement, so we have to find movement that the patient enjoys doing. Passive treatments, things being done to patients, just don’t work as well.
Dr. Williams: We should be clear – we’re talking primarily about chronic back pain here. For acute back pain, we actually have some decent medications, but acute back pain tends to improve no matter what you do. We don’t have much to offer pharmacologically for chronic low back pain. The best modalities usually involve physical activity of some kind.
Dr. Watto: Let’s discuss the evaluation of back pain. Something that always comes up: Should we order imaging, and is there a right time to get it? Dr. Baraki was very clear about when to do imaging. Two big buckets of patients might need imaging.
First, a patient who has a serious underlying condition and you’re using imaging to try to diagnose it; or in a chronic setting, a patient who needs surgery, and imaging is part of the presurgical evaluation. We talked about red flags.
The red flags are major trauma, where we have reason to believe there might be something going on – if we strongly suspect infection, or the patient is injecting drugs. If the patient has a history of cancer, we would be worried that they might have a recurrence. Those are some of the main red flags. With a patient who has osteoporosis or is on chronic steroids, you might even be able to get by with plain films instead of an MRI to look for fracture.
The other thing I wanted to ask you about is, when should we get imaging? Are there any pitfalls we need to worry about?
Dr. Williams: I always like podcasts I’m not on because I enjoy listening to them much more. Dr. Baraki talked about the very specific language that is used in radiology reports, such as spondylitis, spondylolysis, and multilevel degenerative disease. They sound bad, but if they are just reframed as age-related degenerative changes, that sounds so much more benign. When discussing with patients, we should avoid medical jargon and say that we saw some changes that we would expect for someone of your age. That sounds so much better than saying we saw multilevel degenerative disease, which sounds like an alarming pathology if you’re not a physician. Without being inaccurate, we should frame the discussion such that we aren’t providing a very specific diagnosis, because that is rarely the case with chronic low back pain. Typically, many things are going on and you may never identify a single unifying diagnosis, which doesn’t tend to help anyway.
Dr. Watto: There’s evidence showing that if the radiology report uses clinical terminology that both clinician and patient think of as less serious, they are less likely to proceed to more invasive treatments. Calling an episode of back pain a “lumbar strain” helps the patient understand that this is a pretty common thing. Almost everyone is going to have an episode of back pain at some point in their life, and almost all of them will get better. Most of the time there’s no serious underlying condition.
This was a great discussion with Dr. Baraki. Click on Back Pain Update with Dr Austin Baraki to hear the full discussion. Until next time, I’ve been Dr. Matthew Frank Watto.
Dr. Williams: And I’m Dr. Paul Nelson Williams.
Dr. Watto is Clinical Assistant Professor, Department of Medicine, University of Pennsylvania, Philadelphia. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, Temple University, Philadelphia. Neither reported any conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Matthew F. Watto, MD: Welcome back to The Curbsiders. On tonight’s episode, we are going to be talking about back pain. I’ll use one of my famous teaching techniques: If the patient has any kind of back pain, they should just not move. Right?
Paul N. Williams, MD: That’s right, Matt – we should recommend bedrest until they get better for anyone who has any back pain? No. For back pain, early activity and exercise are great. Patients are often concerned that physical therapy will make their pain worse, so they don’t exercise. This misunderstanding is not surprising. They believe that if they are experiencing pain, it’s facilitating more damage, which is not necessarily the case. It will get better, and a little bit of anticipatory guidance goes a long way in terms of managing patient expectations related to early mobilization, early exercise, and physical therapy.
Dr. Watto: Absolutely. One of the goals of treatment is symptom relief to the extent that we’re able to achieve. We’re not expecting the pain to go to zero. That just doesn’t happen, especially if someone’s on a medication long term. Another goal is return to function. We want them sleeping. We want them to be able to tolerate movement.
We have medications – NSAIDs and muscle relaxants, which are actually tranquilizers. But most therapy for back pain doesn’t involve medications. It involves active movement, so we have to find movement that the patient enjoys doing. Passive treatments, things being done to patients, just don’t work as well.
Dr. Williams: We should be clear – we’re talking primarily about chronic back pain here. For acute back pain, we actually have some decent medications, but acute back pain tends to improve no matter what you do. We don’t have much to offer pharmacologically for chronic low back pain. The best modalities usually involve physical activity of some kind.
Dr. Watto: Let’s discuss the evaluation of back pain. Something that always comes up: Should we order imaging, and is there a right time to get it? Dr. Baraki was very clear about when to do imaging. Two big buckets of patients might need imaging.
First, a patient who has a serious underlying condition and you’re using imaging to try to diagnose it; or in a chronic setting, a patient who needs surgery, and imaging is part of the presurgical evaluation. We talked about red flags.
The red flags are major trauma, where we have reason to believe there might be something going on – if we strongly suspect infection, or the patient is injecting drugs. If the patient has a history of cancer, we would be worried that they might have a recurrence. Those are some of the main red flags. With a patient who has osteoporosis or is on chronic steroids, you might even be able to get by with plain films instead of an MRI to look for fracture.
The other thing I wanted to ask you about is, when should we get imaging? Are there any pitfalls we need to worry about?
Dr. Williams: I always like podcasts I’m not on because I enjoy listening to them much more. Dr. Baraki talked about the very specific language that is used in radiology reports, such as spondylitis, spondylolysis, and multilevel degenerative disease. They sound bad, but if they are just reframed as age-related degenerative changes, that sounds so much more benign. When discussing with patients, we should avoid medical jargon and say that we saw some changes that we would expect for someone of your age. That sounds so much better than saying we saw multilevel degenerative disease, which sounds like an alarming pathology if you’re not a physician. Without being inaccurate, we should frame the discussion such that we aren’t providing a very specific diagnosis, because that is rarely the case with chronic low back pain. Typically, many things are going on and you may never identify a single unifying diagnosis, which doesn’t tend to help anyway.
Dr. Watto: There’s evidence showing that if the radiology report uses clinical terminology that both clinician and patient think of as less serious, they are less likely to proceed to more invasive treatments. Calling an episode of back pain a “lumbar strain” helps the patient understand that this is a pretty common thing. Almost everyone is going to have an episode of back pain at some point in their life, and almost all of them will get better. Most of the time there’s no serious underlying condition.
This was a great discussion with Dr. Baraki. Click on Back Pain Update with Dr Austin Baraki to hear the full discussion. Until next time, I’ve been Dr. Matthew Frank Watto.
Dr. Williams: And I’m Dr. Paul Nelson Williams.
Dr. Watto is Clinical Assistant Professor, Department of Medicine, University of Pennsylvania, Philadelphia. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, Temple University, Philadelphia. Neither reported any conflicts of interest.
A version of this article first appeared on Medscape.com.
Scientific advances and dietary measures to slow down aging
These findings are closer than ever to being applied in older adults. Currently, diet is the most accessible form of intervention, but it is appropriate to clarify current myths and realities.
An article published in Cell in 2013 summarized for the first time the molecular indicators of aging in mammals. The article had a great impact and served as a knowledge map about aging. Now the authors have updated and extended this knowledge in the same journal.
A barometer of interest in the topic is that approximately 300,000 articles on aging have been published since 2013, which is as many as were published during the previous century. In addition, almost 80 experiments have been conducted with mammals, including humans, that confirm that interventions in the aging process can prevent, delay, and even avoid age-related diseases such as cancer.
María A. Blasco, MD, scientific director of the National Cancer Research Center, an international leader in telomere research and coauthor of the study, noted on the institution’s website, “The spectacular advances in recent years to increase the longevity of model organisms, including in mammals, indicate that it will be important to develop rational strategies to intervene in human aging.”
Eighty experimental interventions
The new article verifies the conclusions of the analysis carried out a decade ago. “Now there is much more investment, and we are closer to applying basic knowledge to new ways of treating diseases,” said Dr. Blasco. The researchers identified nine indicators of aging – molecular signatures that mark the progress of the process and on which it was possible to act to prolong life.
They also point to four primary causes of aging: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation. These are strongly interconnected processes. Aging results from their joint action, which is why there are multiple ways to act on the physiologic process of aging. The new study includes a table with almost 80 recent experimental interventions with mammals (mostly mice) that suggest that it is possible to prolong life or treat age-associated diseases. Some of those studies concern humans; others investigate how to delay aging through diet. “Acting on the diet is one of the most accessible ways to intervene in human aging,” according to the researchers.
Nutrient sensors
Dietary interventions are related to a key indicator of aging: the dysregulation of the nutrient sensing mechanism. This mechanism is the sophisticated network of molecular signals that alert all mammals that food is available.
“Nutrient sensors are therapeutic targets for potential anti-longevity drugs, but health benefits and lifespan extension could also be achieved through dietary interventions. However, the results obtained in this line in our species are still unclear: Clinical trials based on dietary restriction in humans become complicated due to poor compliance, although they suggest positive effects on immunity and inflammation,” wrote the researchers.
Diet and disease
Javier Gómez Pavón, MD, head of geriatrics at Red Cross Hospital in Madrid and member of the leadership team of the Spanish Society of Geriatrics and Gerontology, told this news organization, “Currently, the evidence we have indicates that certain types of diet in population cohort studies are associated with a lower incidence and prevalence of certain diseases.”
Dr. Gómez mentioned contrasting examples. “The Mediterranean diet has been shown in different studies to be associated with a lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and a lower risk of cognitive impairment, especially due to its vascular component.”
Eating nuts (e.g., almonds, walnuts) is associated with a less dyslipidemia. A diet rich in fiber is also associated with less colonic digestive pathology, such as constipation and especially colon cancer. In addition, a diet low in fatty meats and rich in fruits and vegetables is associated with less prostate, breast, and colon disease. A diet with adequate protein intake is related to better muscle mass at all ages, and a diet rich in calcium products, such as nuts and dairy products, is linked to better bone mass and less osteoporosis and its consequences.
“At the moment, there is no study that links any type of diet with greater longevity, although in view of these data, it seems logical that a Mediterranean diet rich in fruits, vegetables, vegetables with proteins of animal origin, preferably fish or white meat, avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free aging,” said Dr. Gómez.
Aging indicators
The article expands the aging indicators from 9 to 12 (genomic instability, telomere wear, epigenetic alterations, loss of proteostasis, inactivated macroautophagy, dysregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, depletion of hematopoietic progenitor cells, alteration of intercellular communication, chronic inflammation, and imbalances in the microbiome), which are measurable processes that change with the aging of the organism and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption, even a regression, of aging.
“Each of these indicators should be considered an entry point for future exploration of the aging process, as well as for the development of new antiaging drugs,” the researchers concluded.
A decade ago, it was recognized that telomere shortening was at the origin of age-related diseases, said Dr. Blasco. “It is now emphasized that the generation of mouse models with short telomeres has shown that telomeric wasting is at the origin of prevalent age-associated diseases, such as pulmonary and renal fibrosis.”
The recent study reviews new interventions to delay aging and age-related diseases that act on telomeres. “For example, the activation of telomerase through a gene therapy strategy has shown therapeutic effects in mouse models of pulmonary fibrosis and aplastic anemia,” Dr. Blasco added.
Food fact and fiction
Since diet is currently the most easily accessible element to slow down aging, Dr. Gómez refutes the most widespread myths that are circulating about food and longevity. First, regarding dairy products, it is said that yogurt is not useful for the elderly, since the elderly do not have adequate enzymes to digest yogurt and that it is only for children or young people who are growing. “It is not true. Dairy products are not important for their proteins but for their calcium and vitamin D content. [These are] fundamental elements at all ages, but especially in aging, where there is bone loss secondary to aging itself and an increased risk of osteoporosis and associated fractures. Especially in the elderly, the tragic hip fracture is associated with high morbidity and mortality.”
Another myth is that it is not good to eat fruit with meals. “Due to its rich content in antioxidants and vitamins, it is a fundamental food of the Mediterranean diet. Antioxidants of any type (nuts, vegetables, fruits, etc.) are undoubtedly the most important components against pathological aging (stroke, myocardial infarction, dementia, etc.). It may be true that they can be more easily digested if they are eaten outside of meals, but the important thing is that they be eaten whenever.”
Sugars and meat
“Regarding the ‘fact’ that the sugars in legumes and bread are harmful, it is not true. In addition to sugar, legumes contain fiber and other very important antioxidants, just like bread. The difference is the amount, as in all food. On the contrary, refined sugars, such as pastries, sugary drinks, etc., should be avoided, since they are directly related to cardiovascular disease and obesity,” added Dr. Gómez.
“As for the popular saying, ‘Do not even try meat,’ it is not sound, since red meat and fish, including oily fish, are rich in protein and vitamin B as well as iron and, therefore, are necessary.
“As always, it is the amount that should be limited, especially red meat, not so much oily fish. I would recommend reducing red meat and replacing it with white meat, since the former are rich in saturated fats that produce more cholesterol,” added Dr. Gómez.
Another phrase that circulates around is that wine is food. “Careful. Wine in small quantities, a glass at lunch and dinner, is beneficial due to its antioxidant power, but at more than these amounts, the negative power of alcohol predominates over its benefits,” concluded Dr. Gómez.
Dr. Gómez has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
These findings are closer than ever to being applied in older adults. Currently, diet is the most accessible form of intervention, but it is appropriate to clarify current myths and realities.
An article published in Cell in 2013 summarized for the first time the molecular indicators of aging in mammals. The article had a great impact and served as a knowledge map about aging. Now the authors have updated and extended this knowledge in the same journal.
A barometer of interest in the topic is that approximately 300,000 articles on aging have been published since 2013, which is as many as were published during the previous century. In addition, almost 80 experiments have been conducted with mammals, including humans, that confirm that interventions in the aging process can prevent, delay, and even avoid age-related diseases such as cancer.
María A. Blasco, MD, scientific director of the National Cancer Research Center, an international leader in telomere research and coauthor of the study, noted on the institution’s website, “The spectacular advances in recent years to increase the longevity of model organisms, including in mammals, indicate that it will be important to develop rational strategies to intervene in human aging.”
Eighty experimental interventions
The new article verifies the conclusions of the analysis carried out a decade ago. “Now there is much more investment, and we are closer to applying basic knowledge to new ways of treating diseases,” said Dr. Blasco. The researchers identified nine indicators of aging – molecular signatures that mark the progress of the process and on which it was possible to act to prolong life.
They also point to four primary causes of aging: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation. These are strongly interconnected processes. Aging results from their joint action, which is why there are multiple ways to act on the physiologic process of aging. The new study includes a table with almost 80 recent experimental interventions with mammals (mostly mice) that suggest that it is possible to prolong life or treat age-associated diseases. Some of those studies concern humans; others investigate how to delay aging through diet. “Acting on the diet is one of the most accessible ways to intervene in human aging,” according to the researchers.
Nutrient sensors
Dietary interventions are related to a key indicator of aging: the dysregulation of the nutrient sensing mechanism. This mechanism is the sophisticated network of molecular signals that alert all mammals that food is available.
“Nutrient sensors are therapeutic targets for potential anti-longevity drugs, but health benefits and lifespan extension could also be achieved through dietary interventions. However, the results obtained in this line in our species are still unclear: Clinical trials based on dietary restriction in humans become complicated due to poor compliance, although they suggest positive effects on immunity and inflammation,” wrote the researchers.
Diet and disease
Javier Gómez Pavón, MD, head of geriatrics at Red Cross Hospital in Madrid and member of the leadership team of the Spanish Society of Geriatrics and Gerontology, told this news organization, “Currently, the evidence we have indicates that certain types of diet in population cohort studies are associated with a lower incidence and prevalence of certain diseases.”
Dr. Gómez mentioned contrasting examples. “The Mediterranean diet has been shown in different studies to be associated with a lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and a lower risk of cognitive impairment, especially due to its vascular component.”
Eating nuts (e.g., almonds, walnuts) is associated with a less dyslipidemia. A diet rich in fiber is also associated with less colonic digestive pathology, such as constipation and especially colon cancer. In addition, a diet low in fatty meats and rich in fruits and vegetables is associated with less prostate, breast, and colon disease. A diet with adequate protein intake is related to better muscle mass at all ages, and a diet rich in calcium products, such as nuts and dairy products, is linked to better bone mass and less osteoporosis and its consequences.
“At the moment, there is no study that links any type of diet with greater longevity, although in view of these data, it seems logical that a Mediterranean diet rich in fruits, vegetables, vegetables with proteins of animal origin, preferably fish or white meat, avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free aging,” said Dr. Gómez.
Aging indicators
The article expands the aging indicators from 9 to 12 (genomic instability, telomere wear, epigenetic alterations, loss of proteostasis, inactivated macroautophagy, dysregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, depletion of hematopoietic progenitor cells, alteration of intercellular communication, chronic inflammation, and imbalances in the microbiome), which are measurable processes that change with the aging of the organism and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption, even a regression, of aging.
“Each of these indicators should be considered an entry point for future exploration of the aging process, as well as for the development of new antiaging drugs,” the researchers concluded.
A decade ago, it was recognized that telomere shortening was at the origin of age-related diseases, said Dr. Blasco. “It is now emphasized that the generation of mouse models with short telomeres has shown that telomeric wasting is at the origin of prevalent age-associated diseases, such as pulmonary and renal fibrosis.”
The recent study reviews new interventions to delay aging and age-related diseases that act on telomeres. “For example, the activation of telomerase through a gene therapy strategy has shown therapeutic effects in mouse models of pulmonary fibrosis and aplastic anemia,” Dr. Blasco added.
Food fact and fiction
Since diet is currently the most easily accessible element to slow down aging, Dr. Gómez refutes the most widespread myths that are circulating about food and longevity. First, regarding dairy products, it is said that yogurt is not useful for the elderly, since the elderly do not have adequate enzymes to digest yogurt and that it is only for children or young people who are growing. “It is not true. Dairy products are not important for their proteins but for their calcium and vitamin D content. [These are] fundamental elements at all ages, but especially in aging, where there is bone loss secondary to aging itself and an increased risk of osteoporosis and associated fractures. Especially in the elderly, the tragic hip fracture is associated with high morbidity and mortality.”
Another myth is that it is not good to eat fruit with meals. “Due to its rich content in antioxidants and vitamins, it is a fundamental food of the Mediterranean diet. Antioxidants of any type (nuts, vegetables, fruits, etc.) are undoubtedly the most important components against pathological aging (stroke, myocardial infarction, dementia, etc.). It may be true that they can be more easily digested if they are eaten outside of meals, but the important thing is that they be eaten whenever.”
Sugars and meat
“Regarding the ‘fact’ that the sugars in legumes and bread are harmful, it is not true. In addition to sugar, legumes contain fiber and other very important antioxidants, just like bread. The difference is the amount, as in all food. On the contrary, refined sugars, such as pastries, sugary drinks, etc., should be avoided, since they are directly related to cardiovascular disease and obesity,” added Dr. Gómez.
“As for the popular saying, ‘Do not even try meat,’ it is not sound, since red meat and fish, including oily fish, are rich in protein and vitamin B as well as iron and, therefore, are necessary.
“As always, it is the amount that should be limited, especially red meat, not so much oily fish. I would recommend reducing red meat and replacing it with white meat, since the former are rich in saturated fats that produce more cholesterol,” added Dr. Gómez.
Another phrase that circulates around is that wine is food. “Careful. Wine in small quantities, a glass at lunch and dinner, is beneficial due to its antioxidant power, but at more than these amounts, the negative power of alcohol predominates over its benefits,” concluded Dr. Gómez.
Dr. Gómez has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
These findings are closer than ever to being applied in older adults. Currently, diet is the most accessible form of intervention, but it is appropriate to clarify current myths and realities.
An article published in Cell in 2013 summarized for the first time the molecular indicators of aging in mammals. The article had a great impact and served as a knowledge map about aging. Now the authors have updated and extended this knowledge in the same journal.
A barometer of interest in the topic is that approximately 300,000 articles on aging have been published since 2013, which is as many as were published during the previous century. In addition, almost 80 experiments have been conducted with mammals, including humans, that confirm that interventions in the aging process can prevent, delay, and even avoid age-related diseases such as cancer.
María A. Blasco, MD, scientific director of the National Cancer Research Center, an international leader in telomere research and coauthor of the study, noted on the institution’s website, “The spectacular advances in recent years to increase the longevity of model organisms, including in mammals, indicate that it will be important to develop rational strategies to intervene in human aging.”
Eighty experimental interventions
The new article verifies the conclusions of the analysis carried out a decade ago. “Now there is much more investment, and we are closer to applying basic knowledge to new ways of treating diseases,” said Dr. Blasco. The researchers identified nine indicators of aging – molecular signatures that mark the progress of the process and on which it was possible to act to prolong life.
They also point to four primary causes of aging: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation. These are strongly interconnected processes. Aging results from their joint action, which is why there are multiple ways to act on the physiologic process of aging. The new study includes a table with almost 80 recent experimental interventions with mammals (mostly mice) that suggest that it is possible to prolong life or treat age-associated diseases. Some of those studies concern humans; others investigate how to delay aging through diet. “Acting on the diet is one of the most accessible ways to intervene in human aging,” according to the researchers.
Nutrient sensors
Dietary interventions are related to a key indicator of aging: the dysregulation of the nutrient sensing mechanism. This mechanism is the sophisticated network of molecular signals that alert all mammals that food is available.
“Nutrient sensors are therapeutic targets for potential anti-longevity drugs, but health benefits and lifespan extension could also be achieved through dietary interventions. However, the results obtained in this line in our species are still unclear: Clinical trials based on dietary restriction in humans become complicated due to poor compliance, although they suggest positive effects on immunity and inflammation,” wrote the researchers.
Diet and disease
Javier Gómez Pavón, MD, head of geriatrics at Red Cross Hospital in Madrid and member of the leadership team of the Spanish Society of Geriatrics and Gerontology, told this news organization, “Currently, the evidence we have indicates that certain types of diet in population cohort studies are associated with a lower incidence and prevalence of certain diseases.”
Dr. Gómez mentioned contrasting examples. “The Mediterranean diet has been shown in different studies to be associated with a lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and a lower risk of cognitive impairment, especially due to its vascular component.”
Eating nuts (e.g., almonds, walnuts) is associated with a less dyslipidemia. A diet rich in fiber is also associated with less colonic digestive pathology, such as constipation and especially colon cancer. In addition, a diet low in fatty meats and rich in fruits and vegetables is associated with less prostate, breast, and colon disease. A diet with adequate protein intake is related to better muscle mass at all ages, and a diet rich in calcium products, such as nuts and dairy products, is linked to better bone mass and less osteoporosis and its consequences.
“At the moment, there is no study that links any type of diet with greater longevity, although in view of these data, it seems logical that a Mediterranean diet rich in fruits, vegetables, vegetables with proteins of animal origin, preferably fish or white meat, avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free aging,” said Dr. Gómez.
Aging indicators
The article expands the aging indicators from 9 to 12 (genomic instability, telomere wear, epigenetic alterations, loss of proteostasis, inactivated macroautophagy, dysregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, depletion of hematopoietic progenitor cells, alteration of intercellular communication, chronic inflammation, and imbalances in the microbiome), which are measurable processes that change with the aging of the organism and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption, even a regression, of aging.
“Each of these indicators should be considered an entry point for future exploration of the aging process, as well as for the development of new antiaging drugs,” the researchers concluded.
A decade ago, it was recognized that telomere shortening was at the origin of age-related diseases, said Dr. Blasco. “It is now emphasized that the generation of mouse models with short telomeres has shown that telomeric wasting is at the origin of prevalent age-associated diseases, such as pulmonary and renal fibrosis.”
The recent study reviews new interventions to delay aging and age-related diseases that act on telomeres. “For example, the activation of telomerase through a gene therapy strategy has shown therapeutic effects in mouse models of pulmonary fibrosis and aplastic anemia,” Dr. Blasco added.
Food fact and fiction
Since diet is currently the most easily accessible element to slow down aging, Dr. Gómez refutes the most widespread myths that are circulating about food and longevity. First, regarding dairy products, it is said that yogurt is not useful for the elderly, since the elderly do not have adequate enzymes to digest yogurt and that it is only for children or young people who are growing. “It is not true. Dairy products are not important for their proteins but for their calcium and vitamin D content. [These are] fundamental elements at all ages, but especially in aging, where there is bone loss secondary to aging itself and an increased risk of osteoporosis and associated fractures. Especially in the elderly, the tragic hip fracture is associated with high morbidity and mortality.”
Another myth is that it is not good to eat fruit with meals. “Due to its rich content in antioxidants and vitamins, it is a fundamental food of the Mediterranean diet. Antioxidants of any type (nuts, vegetables, fruits, etc.) are undoubtedly the most important components against pathological aging (stroke, myocardial infarction, dementia, etc.). It may be true that they can be more easily digested if they are eaten outside of meals, but the important thing is that they be eaten whenever.”
Sugars and meat
“Regarding the ‘fact’ that the sugars in legumes and bread are harmful, it is not true. In addition to sugar, legumes contain fiber and other very important antioxidants, just like bread. The difference is the amount, as in all food. On the contrary, refined sugars, such as pastries, sugary drinks, etc., should be avoided, since they are directly related to cardiovascular disease and obesity,” added Dr. Gómez.
“As for the popular saying, ‘Do not even try meat,’ it is not sound, since red meat and fish, including oily fish, are rich in protein and vitamin B as well as iron and, therefore, are necessary.
“As always, it is the amount that should be limited, especially red meat, not so much oily fish. I would recommend reducing red meat and replacing it with white meat, since the former are rich in saturated fats that produce more cholesterol,” added Dr. Gómez.
Another phrase that circulates around is that wine is food. “Careful. Wine in small quantities, a glass at lunch and dinner, is beneficial due to its antioxidant power, but at more than these amounts, the negative power of alcohol predominates over its benefits,” concluded Dr. Gómez.
Dr. Gómez has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
FROM CELL
Higher dementia risk in women explained?
a study suggests.
Prior research has found a higher lifetime dementia risk in women, and one explanation cited has been that women tend to live longer than men.
However, this new analysis of data from nearly 30,000 people in 18 countries found almost no evidence of sex differences in most known risk factors for dementia, including age.
The risk of dementia among women was significantly higher in poorer countries, pointing to economic disadvantages as a possible explanation.
“In general, we found that the greater dementia risk found in women compared to men was more pronounced in poorer countries, which points to the need for greater efforts to narrow the gaps in health disparities between women and men in these countries,” lead investigator Jessica Gong, MSc, a doctoral student at the George Institute for Global Health, Newtown, Australia, told this news organization. “It is likely that socioeconomic factors are potentially more important than biological factors when assessing dementia risk.”
The findings were published online in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Global data
Most previous studies that examined sex differences in dementia risk were conducted in high-income countries, Ms. Gong noted, leaving a gap in the literature on risk in low- and middle-income countries.
To address this issue, researchers conducted an individual participant meta-analysis of 21 studies from the Cohort Studies of Memory in an International Consortium. Data analysis included information on 29,850 people from 18 countries on six continents. None of the participants had dementia at baseline, and the average age was 71.6 years.
Over a median of 4.6 years, incident dementia was reported in 2,089 people, 66% of whom were women.
Overall, women had higher dementia risk (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) than men, but the rates were highest in low- to middle-income economies (HR, 1.73; P = .03).
Dementia risk in women was higher than in men in 14 countries. Risk was highest in Nigeria, where dementia risk was more than double in women (aHR, 2.11; 95% CI, 1.46-3.04), and lowest in Brazil, where risk was 46% lower in women than in men (aHR, 0.54; 95% CI, 0.29-1.00).
In the United States, dementia risk was 7% higher in women than men (aHR, 1.07; 0.73-1.57).
Similar risk factors
In both women and men, older age, diabetes, depression, hearing impairment, and apo E–epsilon 4 carriage were associated with a greater risk of dementia, and more years of education, higher hip circumference, current alcohol use (vs. never), and high physical activity (vs. none to minimal) were associated with a lower risk of dementia.
Among all these risk factors, sex differences were only significant for longer education and former alcohol use, with both demonstrating a stronger association in men than women.
Global dementia rates are expected to triple over the next 25 years unless steps are taken to reduce risk factors. A 2020 report found that dementia risk could be reduced by addressing 12 modifiable risk factors, including obesity, air pollution, diabetes, social isolation, and hypertension. All of these risk factors are more common in low- to middle-income countries, Ms. Gong noted.
“These findings justify ongoing efforts to support programs to improve sex and gender equity in brain health, particularly in underrepresented and underserved populations, in turn to narrow the gaps within and between country,” Ms. Gong said.
Understanding the puzzle
Commenting on the findings for Medscape Medical News, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, said the findings add to the body of work about sex differences in dementia risk.
“This is an interesting study looking at risk factors for dementia and suggests that, while some risk factors are more pronounced in men than in women, women may be more at risk of progressing to dementia,” Dr. Snyder said. “The findings outline the importance of understanding how the underlying biology, particularly biology that differs in males and females, may be contributing to risk.”
Data on the country and geographical variations highlighted in the study also point to a potential risk influencer, she said.
“Studying geography-specific risk factors is important because it helps us understand the ‘why’ behind geographic differences in dementia risk,” Dr. Snyder said. “This type of collaboration among countries and researchers is essential for us to understand these puzzle pieces.”
Funding for the study was provided by the U.K. Medical Research Council Skills Development Fellowship, Australian National Health and Medical Research Council Investigator Grant, National Institute on Aging, among others. See the original article for full funding sources. Ms. Gong reported no relevant financial conflicts. Dr. Snyder is employed by the Alzheimer’s Association.
A version of this article originally appeared on Medscape.com.
a study suggests.
Prior research has found a higher lifetime dementia risk in women, and one explanation cited has been that women tend to live longer than men.
However, this new analysis of data from nearly 30,000 people in 18 countries found almost no evidence of sex differences in most known risk factors for dementia, including age.
The risk of dementia among women was significantly higher in poorer countries, pointing to economic disadvantages as a possible explanation.
“In general, we found that the greater dementia risk found in women compared to men was more pronounced in poorer countries, which points to the need for greater efforts to narrow the gaps in health disparities between women and men in these countries,” lead investigator Jessica Gong, MSc, a doctoral student at the George Institute for Global Health, Newtown, Australia, told this news organization. “It is likely that socioeconomic factors are potentially more important than biological factors when assessing dementia risk.”
The findings were published online in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Global data
Most previous studies that examined sex differences in dementia risk were conducted in high-income countries, Ms. Gong noted, leaving a gap in the literature on risk in low- and middle-income countries.
To address this issue, researchers conducted an individual participant meta-analysis of 21 studies from the Cohort Studies of Memory in an International Consortium. Data analysis included information on 29,850 people from 18 countries on six continents. None of the participants had dementia at baseline, and the average age was 71.6 years.
Over a median of 4.6 years, incident dementia was reported in 2,089 people, 66% of whom were women.
Overall, women had higher dementia risk (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) than men, but the rates were highest in low- to middle-income economies (HR, 1.73; P = .03).
Dementia risk in women was higher than in men in 14 countries. Risk was highest in Nigeria, where dementia risk was more than double in women (aHR, 2.11; 95% CI, 1.46-3.04), and lowest in Brazil, where risk was 46% lower in women than in men (aHR, 0.54; 95% CI, 0.29-1.00).
In the United States, dementia risk was 7% higher in women than men (aHR, 1.07; 0.73-1.57).
Similar risk factors
In both women and men, older age, diabetes, depression, hearing impairment, and apo E–epsilon 4 carriage were associated with a greater risk of dementia, and more years of education, higher hip circumference, current alcohol use (vs. never), and high physical activity (vs. none to minimal) were associated with a lower risk of dementia.
Among all these risk factors, sex differences were only significant for longer education and former alcohol use, with both demonstrating a stronger association in men than women.
Global dementia rates are expected to triple over the next 25 years unless steps are taken to reduce risk factors. A 2020 report found that dementia risk could be reduced by addressing 12 modifiable risk factors, including obesity, air pollution, diabetes, social isolation, and hypertension. All of these risk factors are more common in low- to middle-income countries, Ms. Gong noted.
“These findings justify ongoing efforts to support programs to improve sex and gender equity in brain health, particularly in underrepresented and underserved populations, in turn to narrow the gaps within and between country,” Ms. Gong said.
Understanding the puzzle
Commenting on the findings for Medscape Medical News, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, said the findings add to the body of work about sex differences in dementia risk.
“This is an interesting study looking at risk factors for dementia and suggests that, while some risk factors are more pronounced in men than in women, women may be more at risk of progressing to dementia,” Dr. Snyder said. “The findings outline the importance of understanding how the underlying biology, particularly biology that differs in males and females, may be contributing to risk.”
Data on the country and geographical variations highlighted in the study also point to a potential risk influencer, she said.
“Studying geography-specific risk factors is important because it helps us understand the ‘why’ behind geographic differences in dementia risk,” Dr. Snyder said. “This type of collaboration among countries and researchers is essential for us to understand these puzzle pieces.”
Funding for the study was provided by the U.K. Medical Research Council Skills Development Fellowship, Australian National Health and Medical Research Council Investigator Grant, National Institute on Aging, among others. See the original article for full funding sources. Ms. Gong reported no relevant financial conflicts. Dr. Snyder is employed by the Alzheimer’s Association.
A version of this article originally appeared on Medscape.com.
a study suggests.
Prior research has found a higher lifetime dementia risk in women, and one explanation cited has been that women tend to live longer than men.
However, this new analysis of data from nearly 30,000 people in 18 countries found almost no evidence of sex differences in most known risk factors for dementia, including age.
The risk of dementia among women was significantly higher in poorer countries, pointing to economic disadvantages as a possible explanation.
“In general, we found that the greater dementia risk found in women compared to men was more pronounced in poorer countries, which points to the need for greater efforts to narrow the gaps in health disparities between women and men in these countries,” lead investigator Jessica Gong, MSc, a doctoral student at the George Institute for Global Health, Newtown, Australia, told this news organization. “It is likely that socioeconomic factors are potentially more important than biological factors when assessing dementia risk.”
The findings were published online in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Global data
Most previous studies that examined sex differences in dementia risk were conducted in high-income countries, Ms. Gong noted, leaving a gap in the literature on risk in low- and middle-income countries.
To address this issue, researchers conducted an individual participant meta-analysis of 21 studies from the Cohort Studies of Memory in an International Consortium. Data analysis included information on 29,850 people from 18 countries on six continents. None of the participants had dementia at baseline, and the average age was 71.6 years.
Over a median of 4.6 years, incident dementia was reported in 2,089 people, 66% of whom were women.
Overall, women had higher dementia risk (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) than men, but the rates were highest in low- to middle-income economies (HR, 1.73; P = .03).
Dementia risk in women was higher than in men in 14 countries. Risk was highest in Nigeria, where dementia risk was more than double in women (aHR, 2.11; 95% CI, 1.46-3.04), and lowest in Brazil, where risk was 46% lower in women than in men (aHR, 0.54; 95% CI, 0.29-1.00).
In the United States, dementia risk was 7% higher in women than men (aHR, 1.07; 0.73-1.57).
Similar risk factors
In both women and men, older age, diabetes, depression, hearing impairment, and apo E–epsilon 4 carriage were associated with a greater risk of dementia, and more years of education, higher hip circumference, current alcohol use (vs. never), and high physical activity (vs. none to minimal) were associated with a lower risk of dementia.
Among all these risk factors, sex differences were only significant for longer education and former alcohol use, with both demonstrating a stronger association in men than women.
Global dementia rates are expected to triple over the next 25 years unless steps are taken to reduce risk factors. A 2020 report found that dementia risk could be reduced by addressing 12 modifiable risk factors, including obesity, air pollution, diabetes, social isolation, and hypertension. All of these risk factors are more common in low- to middle-income countries, Ms. Gong noted.
“These findings justify ongoing efforts to support programs to improve sex and gender equity in brain health, particularly in underrepresented and underserved populations, in turn to narrow the gaps within and between country,” Ms. Gong said.
Understanding the puzzle
Commenting on the findings for Medscape Medical News, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, said the findings add to the body of work about sex differences in dementia risk.
“This is an interesting study looking at risk factors for dementia and suggests that, while some risk factors are more pronounced in men than in women, women may be more at risk of progressing to dementia,” Dr. Snyder said. “The findings outline the importance of understanding how the underlying biology, particularly biology that differs in males and females, may be contributing to risk.”
Data on the country and geographical variations highlighted in the study also point to a potential risk influencer, she said.
“Studying geography-specific risk factors is important because it helps us understand the ‘why’ behind geographic differences in dementia risk,” Dr. Snyder said. “This type of collaboration among countries and researchers is essential for us to understand these puzzle pieces.”
Funding for the study was provided by the U.K. Medical Research Council Skills Development Fellowship, Australian National Health and Medical Research Council Investigator Grant, National Institute on Aging, among others. See the original article for full funding sources. Ms. Gong reported no relevant financial conflicts. Dr. Snyder is employed by the Alzheimer’s Association.
A version of this article originally appeared on Medscape.com.
FROM ALZHEIMER’S & DEMENTIA
Diabetes drug tied to lower dementia risk
new research suggests.
Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.
However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.
“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.
However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.
This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.
The results were published online in Neurology.
Dose-response relationship
Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.
This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.
Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.
Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.
Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.
There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).
A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
Several limitations
The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).
The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.
The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).
“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.
However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.
The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.
There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
More data needed
In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”
However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.
They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.
They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.
“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.
For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.
The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.
However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.
“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.
However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.
This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.
The results were published online in Neurology.
Dose-response relationship
Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.
This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.
Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.
Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.
Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.
There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).
A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
Several limitations
The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).
The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.
The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).
“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.
However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.
The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.
There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
More data needed
In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”
However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.
They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.
They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.
“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.
For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.
The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.
However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.
“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.
However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.
This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.
The results were published online in Neurology.
Dose-response relationship
Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.
This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.
Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.
Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.
Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.
There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).
A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
Several limitations
The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).
The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.
The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).
“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.
However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.
The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.
There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
More data needed
In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”
However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.
They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.
They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.
“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.
For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.
The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM NEUROLOGY
Not testing VO2 max in your older patients? Here’s why you should
Once the focus of cyclists and other elite athletes, VO2 max has in recent years caught the attention of geriatricians, who have linked the measure to maximum functional capacity – an umbrella term for the body’s ability to perform aerobic exercise.
“Function is prognostic of mortality,” said Daniel E. Forman, MD, FAHA, FACC, professor of medicine and chair of the section of geriatric cardiology at the University of Pittsburgh Medical Center. “If you aren’t looking at that, you’re missing the boat.”
Although cardiopulmonary exercise testing (CPET) remains the gold standard for assessing VO2 max, Dr. Forman said clinicians often overlook CPET because it is old.
Getting precise
As a person ages, the amount of physical activity needed to stay fit varies, depending on genes, health, and fitness history. Measuring VO2 max can help doctors better prescribe physical activity, both with regard to specific exercises and for how long, Claudio Gil Araújo, MD, PhD, dean of research and education at the Exercise Medicine Clinic at CLINIMEX in Rio de Janeiro, Brazil, told this news organization. The test can also measure progress.
“Guidelines talk about how much exercise you should do every week, but it’s somewhat misleading because the health outcomes are much more linked to physical fitness than the amount of exercise you do,” Dr. Araújo said. Treating a patient with hypertension requires an individualized approach. “The same thing is true with exercise,” he said.
A person with high aerobic fitness, either because of favorable genetics or because he or she has maintained good fitness by exercising, may need less activity, but 200 minutes per week may not be enough for someone else.
In his own lab, Dr. Araújo is following “dozens” of men and women who have been able to increase their ability to exercise – especially high-intensity activity – over time. And their VO2 max readings have risen, he said.
Getting patients moving and collecting data on VO2 max is the most precise way to measure aerobic fitness. But the test is far from a staple in primary care.
Dr. Araújo said a growing body of research has long shown VO2 max to be a significant determinant of health and one that physicians should be paying closer attention to, especially for aging patients.
“If someone has a low VO2 max, the treatment to correct this unfavorable health profile is to increase exercise levels,” Dr. Araújo said. “This is a very relevant public health message.”
Investigators have found that inactivity increases a person’s risk of dying from an atherosclerotic cardiovascular disease event by about the same amount as smoking, and that a sedentary lifestyle increases with age . A patient’s fitness is crucial to his or her overall health, and VO2 max can play a key role. Poor performance on CPET could be a warning regarding a number of conditions, particularly cardiovascular and lung disease, Dr. Araújo said.
Indeed, acing the CPET is not easy.
“Your joints have to be normal, you can’t have low potassium, low sodium, or high blood sugar, your heart has to pump well, your blood vessels have to be healthy,” said Thomas Allison, PhD, MPH, director of the Integrated Stress Testing Center and the Sports Cardiology Clinic at Mayo Clinic, in Rochester, Minn. “All of those things can show up on the treadmill in terms of your VO2 max.”
Low VO2 max can be a physician’s first indication to investigate further. A review published in November 2022 in the International Journal of Cardiology Cardiovascular Risk and Prevention outlined what cross-sectional and longitudinal studies have documented regarding how VO2 max changes as people age. From ages 18 to 35, VO2 max remains fairly consistent. Between 35 and 55, it drops slightly but inexorably before falling sharply, if inconsistently. This inconsistency is where the important data lie.
“That lower level of physical activity may just be a behavioral change that needs to be reversed, or it could be a change that has been forced by underlying occult disease,” Dr. Allison said. That older people can’t run as fast as young people or are more likely to die in a given period than young people is not surprising. “The question is, at any given age, does your fitness level predict good health outcomes?” he said. “And the answer is yes.”
Fitness should be treated as any other data point, he added.
“If I want to know your blood pressure, I’m going to check your blood pressure; I’m not going to just ask you what it is,” Dr. Allison said. “If I ask if you have any limitations or symptoms with exercise or how physically active you are, if possible, I want to check that.”
Culture shift
Dr. Forman acknowledged that VO2 max tests can be difficult and expensive to administer in offices that aren’t already equipped with CPET machines. He said conducting other assessments, such as observing the patient performing a short walk, won’t provide as accurate data but is better than not assessing function at all.
“Specialists all have different things they measure, but function is the common denominator. For an aging population, it is the number one thing we should be looking at,” Dr. Forman said. “It’s a skill set, it’s an investment, it’s a change in culture at a time when cardiologists are obsessed with getting the latest imaging machines.”
Dr. Allison said all cardiologists should assess their patients’ VO2 max and that family medicine doctors should use the test for certain patients, such as those who have gained an unusual amount of weight or report being out of breath more than usual.
“We have all sorts of things that can go wrong with us as we get older, but if we’re sitting in a doctor’s office, it may not be apparent what they are,” Dr. Allison said. “We have to get patients up and moving.”
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Once the focus of cyclists and other elite athletes, VO2 max has in recent years caught the attention of geriatricians, who have linked the measure to maximum functional capacity – an umbrella term for the body’s ability to perform aerobic exercise.
“Function is prognostic of mortality,” said Daniel E. Forman, MD, FAHA, FACC, professor of medicine and chair of the section of geriatric cardiology at the University of Pittsburgh Medical Center. “If you aren’t looking at that, you’re missing the boat.”
Although cardiopulmonary exercise testing (CPET) remains the gold standard for assessing VO2 max, Dr. Forman said clinicians often overlook CPET because it is old.
Getting precise
As a person ages, the amount of physical activity needed to stay fit varies, depending on genes, health, and fitness history. Measuring VO2 max can help doctors better prescribe physical activity, both with regard to specific exercises and for how long, Claudio Gil Araújo, MD, PhD, dean of research and education at the Exercise Medicine Clinic at CLINIMEX in Rio de Janeiro, Brazil, told this news organization. The test can also measure progress.
“Guidelines talk about how much exercise you should do every week, but it’s somewhat misleading because the health outcomes are much more linked to physical fitness than the amount of exercise you do,” Dr. Araújo said. Treating a patient with hypertension requires an individualized approach. “The same thing is true with exercise,” he said.
A person with high aerobic fitness, either because of favorable genetics or because he or she has maintained good fitness by exercising, may need less activity, but 200 minutes per week may not be enough for someone else.
In his own lab, Dr. Araújo is following “dozens” of men and women who have been able to increase their ability to exercise – especially high-intensity activity – over time. And their VO2 max readings have risen, he said.
Getting patients moving and collecting data on VO2 max is the most precise way to measure aerobic fitness. But the test is far from a staple in primary care.
Dr. Araújo said a growing body of research has long shown VO2 max to be a significant determinant of health and one that physicians should be paying closer attention to, especially for aging patients.
“If someone has a low VO2 max, the treatment to correct this unfavorable health profile is to increase exercise levels,” Dr. Araújo said. “This is a very relevant public health message.”
Investigators have found that inactivity increases a person’s risk of dying from an atherosclerotic cardiovascular disease event by about the same amount as smoking, and that a sedentary lifestyle increases with age . A patient’s fitness is crucial to his or her overall health, and VO2 max can play a key role. Poor performance on CPET could be a warning regarding a number of conditions, particularly cardiovascular and lung disease, Dr. Araújo said.
Indeed, acing the CPET is not easy.
“Your joints have to be normal, you can’t have low potassium, low sodium, or high blood sugar, your heart has to pump well, your blood vessels have to be healthy,” said Thomas Allison, PhD, MPH, director of the Integrated Stress Testing Center and the Sports Cardiology Clinic at Mayo Clinic, in Rochester, Minn. “All of those things can show up on the treadmill in terms of your VO2 max.”
Low VO2 max can be a physician’s first indication to investigate further. A review published in November 2022 in the International Journal of Cardiology Cardiovascular Risk and Prevention outlined what cross-sectional and longitudinal studies have documented regarding how VO2 max changes as people age. From ages 18 to 35, VO2 max remains fairly consistent. Between 35 and 55, it drops slightly but inexorably before falling sharply, if inconsistently. This inconsistency is where the important data lie.
“That lower level of physical activity may just be a behavioral change that needs to be reversed, or it could be a change that has been forced by underlying occult disease,” Dr. Allison said. That older people can’t run as fast as young people or are more likely to die in a given period than young people is not surprising. “The question is, at any given age, does your fitness level predict good health outcomes?” he said. “And the answer is yes.”
Fitness should be treated as any other data point, he added.
“If I want to know your blood pressure, I’m going to check your blood pressure; I’m not going to just ask you what it is,” Dr. Allison said. “If I ask if you have any limitations or symptoms with exercise or how physically active you are, if possible, I want to check that.”
Culture shift
Dr. Forman acknowledged that VO2 max tests can be difficult and expensive to administer in offices that aren’t already equipped with CPET machines. He said conducting other assessments, such as observing the patient performing a short walk, won’t provide as accurate data but is better than not assessing function at all.
“Specialists all have different things they measure, but function is the common denominator. For an aging population, it is the number one thing we should be looking at,” Dr. Forman said. “It’s a skill set, it’s an investment, it’s a change in culture at a time when cardiologists are obsessed with getting the latest imaging machines.”
Dr. Allison said all cardiologists should assess their patients’ VO2 max and that family medicine doctors should use the test for certain patients, such as those who have gained an unusual amount of weight or report being out of breath more than usual.
“We have all sorts of things that can go wrong with us as we get older, but if we’re sitting in a doctor’s office, it may not be apparent what they are,” Dr. Allison said. “We have to get patients up and moving.”
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Once the focus of cyclists and other elite athletes, VO2 max has in recent years caught the attention of geriatricians, who have linked the measure to maximum functional capacity – an umbrella term for the body’s ability to perform aerobic exercise.
“Function is prognostic of mortality,” said Daniel E. Forman, MD, FAHA, FACC, professor of medicine and chair of the section of geriatric cardiology at the University of Pittsburgh Medical Center. “If you aren’t looking at that, you’re missing the boat.”
Although cardiopulmonary exercise testing (CPET) remains the gold standard for assessing VO2 max, Dr. Forman said clinicians often overlook CPET because it is old.
Getting precise
As a person ages, the amount of physical activity needed to stay fit varies, depending on genes, health, and fitness history. Measuring VO2 max can help doctors better prescribe physical activity, both with regard to specific exercises and for how long, Claudio Gil Araújo, MD, PhD, dean of research and education at the Exercise Medicine Clinic at CLINIMEX in Rio de Janeiro, Brazil, told this news organization. The test can also measure progress.
“Guidelines talk about how much exercise you should do every week, but it’s somewhat misleading because the health outcomes are much more linked to physical fitness than the amount of exercise you do,” Dr. Araújo said. Treating a patient with hypertension requires an individualized approach. “The same thing is true with exercise,” he said.
A person with high aerobic fitness, either because of favorable genetics or because he or she has maintained good fitness by exercising, may need less activity, but 200 minutes per week may not be enough for someone else.
In his own lab, Dr. Araújo is following “dozens” of men and women who have been able to increase their ability to exercise – especially high-intensity activity – over time. And their VO2 max readings have risen, he said.
Getting patients moving and collecting data on VO2 max is the most precise way to measure aerobic fitness. But the test is far from a staple in primary care.
Dr. Araújo said a growing body of research has long shown VO2 max to be a significant determinant of health and one that physicians should be paying closer attention to, especially for aging patients.
“If someone has a low VO2 max, the treatment to correct this unfavorable health profile is to increase exercise levels,” Dr. Araújo said. “This is a very relevant public health message.”
Investigators have found that inactivity increases a person’s risk of dying from an atherosclerotic cardiovascular disease event by about the same amount as smoking, and that a sedentary lifestyle increases with age . A patient’s fitness is crucial to his or her overall health, and VO2 max can play a key role. Poor performance on CPET could be a warning regarding a number of conditions, particularly cardiovascular and lung disease, Dr. Araújo said.
Indeed, acing the CPET is not easy.
“Your joints have to be normal, you can’t have low potassium, low sodium, or high blood sugar, your heart has to pump well, your blood vessels have to be healthy,” said Thomas Allison, PhD, MPH, director of the Integrated Stress Testing Center and the Sports Cardiology Clinic at Mayo Clinic, in Rochester, Minn. “All of those things can show up on the treadmill in terms of your VO2 max.”
Low VO2 max can be a physician’s first indication to investigate further. A review published in November 2022 in the International Journal of Cardiology Cardiovascular Risk and Prevention outlined what cross-sectional and longitudinal studies have documented regarding how VO2 max changes as people age. From ages 18 to 35, VO2 max remains fairly consistent. Between 35 and 55, it drops slightly but inexorably before falling sharply, if inconsistently. This inconsistency is where the important data lie.
“That lower level of physical activity may just be a behavioral change that needs to be reversed, or it could be a change that has been forced by underlying occult disease,” Dr. Allison said. That older people can’t run as fast as young people or are more likely to die in a given period than young people is not surprising. “The question is, at any given age, does your fitness level predict good health outcomes?” he said. “And the answer is yes.”
Fitness should be treated as any other data point, he added.
“If I want to know your blood pressure, I’m going to check your blood pressure; I’m not going to just ask you what it is,” Dr. Allison said. “If I ask if you have any limitations or symptoms with exercise or how physically active you are, if possible, I want to check that.”
Culture shift
Dr. Forman acknowledged that VO2 max tests can be difficult and expensive to administer in offices that aren’t already equipped with CPET machines. He said conducting other assessments, such as observing the patient performing a short walk, won’t provide as accurate data but is better than not assessing function at all.
“Specialists all have different things they measure, but function is the common denominator. For an aging population, it is the number one thing we should be looking at,” Dr. Forman said. “It’s a skill set, it’s an investment, it’s a change in culture at a time when cardiologists are obsessed with getting the latest imaging machines.”
Dr. Allison said all cardiologists should assess their patients’ VO2 max and that family medicine doctors should use the test for certain patients, such as those who have gained an unusual amount of weight or report being out of breath more than usual.
“We have all sorts of things that can go wrong with us as we get older, but if we’re sitting in a doctor’s office, it may not be apparent what they are,” Dr. Allison said. “We have to get patients up and moving.”
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Slowing, not stopping, Alzheimer’s a better goal for clinical trials?
and may be a more realistic goal for clinical AD drug trials, a new report suggests.
The report is a yearlong undertaking by an expert work group convened by the Alzheimer’s Association and was prompted, in part, by the fallout from the U.S. Food and Drug Administration’s controversial decision to grant aducanumab (Aduhelm) accelerated approval, which came over the objection of an advisory panel that found the drug was ineffective.
The report’s authors call for a “reframing” of how researchers define “clinically meaningful” in randomized controlled trials (RCTs), noting that it’s time to adjust expectations of outcomes from relatively short clinical trials.
“Without lowering the bar, are we expecting too much from a clinical trial by expecting that unless the disease is halted in its tracks and there’s no progression, we failed at treatment?” the report’s lead author and group leader Ronald C. Petersen, MD, PhD, lead author, chair of the work group, and professor of neurology at the Mayo Clinic, Rochester, Minn., told this news organization.
Interpretations of clinical meaningfulness are used in the drug approval process and in decisions about whether an insurer will cover the cost of treatment, the authors note.
While the report doesn’t provide a consensus definition of clinically meaningful benefit, it does offer a starting point for a conversation about how the phrase should be defined in the context of RCTs for disease-modifying therapies (DMTs) in AD, Dr. Petersen said.
“What we tried to do was to put it into some kind of perspective and at least have people reflect on this: If you’re going to design the perfect drug trial in Alzheimer’s disease, what would it be? We wanted to get people to think about it without digging in their heels for or against,” he added.
The report was published online in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.
A proactive measure
The expert group began its work in January 2022, less than a year after the FDA approved aducanumab. Since the panel began its work, the FDA has approved a second AD drug, lecanemab (Leqembi), and denied accelerated approval of a third medication, donanemab.
“At the time we started this group, we had one approved treatment, and we just knew that there were others on the way, and we needed to be prepared to have this conversation and be more proactive than reactive,” Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association and co-author of the report, said in an interview.
The work group suggests that simply slowing disease progression might be a desired goal for drug trials, especially early on, before cognition and memory are affected.
They also note that a benefit identified during an 18-month clinical trial may ultimately lead to even more meaningful changes over coming years, well beyond the trial’s end.
In addition, the report authors call for the development of better research tools to more accurately assess meaningful change. The Clinical Dementia Rating (CDR) scale is currently the key instrument used as a primary outcome measure in RCTs. However, the report’s authors note that it may not be adequate to measure meaningful change in early-stage disease.
“Developing better tools certainly should be on the radar screen for all of us, because I think we can do better,” Dr. Petersen said. “The CDR, as good as it is and as long as it’s been used in the field, is a pretty blunt instrument, and it’s the result of subjective ratings.”
‘Quality of mind’
Jason Karlawish, MD, professor of medicine, medical ethics, health policy, and neurology at the University of Pennsylvania, Philadelphia, said measuring the actual impact of a drug on a patient’s disease and quality of life has been a hot topic in the AD field for some time, but settling on a definition of “clinically meaningful” that everyone agrees upon will be a challenge.
“I think the idea of ‘clinically meaningful’ is truly a socially constructed idea,” said Dr. Karlawish, co-director of Penn’s Memory Center, who did not work on the report.
“You can come up with objective measures of cognition, but a measure to call something ‘clinically meaningful’ ultimately requires some sort of negotiated social order among clinicians and patients and others who have immediate interest in the health and well-being of the patient.”
Dr. Karlawish added that he’s interested in the conversations the report might prompt and the challenges it could highlight, especially when it comes to how meaningful clinical benefit can be measured, regardless of how it’s defined.
“Hidden in this conversation about clinically meaningful treatments in Alzheimer’s disease is, frankly, not quality of life, but quality of mind,” said Dr. Karlawish. “No measure captures acceptably the very thing that everyone actually cares a lot about and why we view this disease as so dreadful, which is damage to our mind.”
More evidence needed
The development of such tools will take time. What does that mean for drugs already in the pipeline? Members of the work group argue that those trials must move forward at the same time new tools are being created.
“We need to continue to refine, develop better instruments, [and] develop tools that are going to assess the disease in its more subtle features early on, even in the so-called ‘pre-symptomatic’ stage of the disease,” said lead author Dr. Petersen. “We shouldn’t wait for the development of that before intervening if we have a drug that seems to work.”
However, not everyone who agrees with the premise of the report agrees with this position, including Joel S. Perlmutter, MD, professor of neurology, Washington University School of Medicine, St. Louis, who also commented on the report.
As reported by this news organization, Dr. Perlmutter was one of three physicians who resigned from the FDA advisory panel that voted against approving aducanumab after the agency moved forward anyway.
“We have to be careful not to recommend DMTs that we hope will help without strong evidence, especially when potential side effects are not trivial,” Dr. Perlmutter said. “We have to have evidence before making these recommendations so we don’t end up harming people more than helping them.”
The report received no specific funding. Dr. Petersen received consulting fees from Roche, Nestle, Merck, Biogen, Eisai, and Genentech. Full disclosures are included in the original article. Dr. Perlmutter and Dr. Karlawish report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
and may be a more realistic goal for clinical AD drug trials, a new report suggests.
The report is a yearlong undertaking by an expert work group convened by the Alzheimer’s Association and was prompted, in part, by the fallout from the U.S. Food and Drug Administration’s controversial decision to grant aducanumab (Aduhelm) accelerated approval, which came over the objection of an advisory panel that found the drug was ineffective.
The report’s authors call for a “reframing” of how researchers define “clinically meaningful” in randomized controlled trials (RCTs), noting that it’s time to adjust expectations of outcomes from relatively short clinical trials.
“Without lowering the bar, are we expecting too much from a clinical trial by expecting that unless the disease is halted in its tracks and there’s no progression, we failed at treatment?” the report’s lead author and group leader Ronald C. Petersen, MD, PhD, lead author, chair of the work group, and professor of neurology at the Mayo Clinic, Rochester, Minn., told this news organization.
Interpretations of clinical meaningfulness are used in the drug approval process and in decisions about whether an insurer will cover the cost of treatment, the authors note.
While the report doesn’t provide a consensus definition of clinically meaningful benefit, it does offer a starting point for a conversation about how the phrase should be defined in the context of RCTs for disease-modifying therapies (DMTs) in AD, Dr. Petersen said.
“What we tried to do was to put it into some kind of perspective and at least have people reflect on this: If you’re going to design the perfect drug trial in Alzheimer’s disease, what would it be? We wanted to get people to think about it without digging in their heels for or against,” he added.
The report was published online in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.
A proactive measure
The expert group began its work in January 2022, less than a year after the FDA approved aducanumab. Since the panel began its work, the FDA has approved a second AD drug, lecanemab (Leqembi), and denied accelerated approval of a third medication, donanemab.
“At the time we started this group, we had one approved treatment, and we just knew that there were others on the way, and we needed to be prepared to have this conversation and be more proactive than reactive,” Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association and co-author of the report, said in an interview.
The work group suggests that simply slowing disease progression might be a desired goal for drug trials, especially early on, before cognition and memory are affected.
They also note that a benefit identified during an 18-month clinical trial may ultimately lead to even more meaningful changes over coming years, well beyond the trial’s end.
In addition, the report authors call for the development of better research tools to more accurately assess meaningful change. The Clinical Dementia Rating (CDR) scale is currently the key instrument used as a primary outcome measure in RCTs. However, the report’s authors note that it may not be adequate to measure meaningful change in early-stage disease.
“Developing better tools certainly should be on the radar screen for all of us, because I think we can do better,” Dr. Petersen said. “The CDR, as good as it is and as long as it’s been used in the field, is a pretty blunt instrument, and it’s the result of subjective ratings.”
‘Quality of mind’
Jason Karlawish, MD, professor of medicine, medical ethics, health policy, and neurology at the University of Pennsylvania, Philadelphia, said measuring the actual impact of a drug on a patient’s disease and quality of life has been a hot topic in the AD field for some time, but settling on a definition of “clinically meaningful” that everyone agrees upon will be a challenge.
“I think the idea of ‘clinically meaningful’ is truly a socially constructed idea,” said Dr. Karlawish, co-director of Penn’s Memory Center, who did not work on the report.
“You can come up with objective measures of cognition, but a measure to call something ‘clinically meaningful’ ultimately requires some sort of negotiated social order among clinicians and patients and others who have immediate interest in the health and well-being of the patient.”
Dr. Karlawish added that he’s interested in the conversations the report might prompt and the challenges it could highlight, especially when it comes to how meaningful clinical benefit can be measured, regardless of how it’s defined.
“Hidden in this conversation about clinically meaningful treatments in Alzheimer’s disease is, frankly, not quality of life, but quality of mind,” said Dr. Karlawish. “No measure captures acceptably the very thing that everyone actually cares a lot about and why we view this disease as so dreadful, which is damage to our mind.”
More evidence needed
The development of such tools will take time. What does that mean for drugs already in the pipeline? Members of the work group argue that those trials must move forward at the same time new tools are being created.
“We need to continue to refine, develop better instruments, [and] develop tools that are going to assess the disease in its more subtle features early on, even in the so-called ‘pre-symptomatic’ stage of the disease,” said lead author Dr. Petersen. “We shouldn’t wait for the development of that before intervening if we have a drug that seems to work.”
However, not everyone who agrees with the premise of the report agrees with this position, including Joel S. Perlmutter, MD, professor of neurology, Washington University School of Medicine, St. Louis, who also commented on the report.
As reported by this news organization, Dr. Perlmutter was one of three physicians who resigned from the FDA advisory panel that voted against approving aducanumab after the agency moved forward anyway.
“We have to be careful not to recommend DMTs that we hope will help without strong evidence, especially when potential side effects are not trivial,” Dr. Perlmutter said. “We have to have evidence before making these recommendations so we don’t end up harming people more than helping them.”
The report received no specific funding. Dr. Petersen received consulting fees from Roche, Nestle, Merck, Biogen, Eisai, and Genentech. Full disclosures are included in the original article. Dr. Perlmutter and Dr. Karlawish report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
and may be a more realistic goal for clinical AD drug trials, a new report suggests.
The report is a yearlong undertaking by an expert work group convened by the Alzheimer’s Association and was prompted, in part, by the fallout from the U.S. Food and Drug Administration’s controversial decision to grant aducanumab (Aduhelm) accelerated approval, which came over the objection of an advisory panel that found the drug was ineffective.
The report’s authors call for a “reframing” of how researchers define “clinically meaningful” in randomized controlled trials (RCTs), noting that it’s time to adjust expectations of outcomes from relatively short clinical trials.
“Without lowering the bar, are we expecting too much from a clinical trial by expecting that unless the disease is halted in its tracks and there’s no progression, we failed at treatment?” the report’s lead author and group leader Ronald C. Petersen, MD, PhD, lead author, chair of the work group, and professor of neurology at the Mayo Clinic, Rochester, Minn., told this news organization.
Interpretations of clinical meaningfulness are used in the drug approval process and in decisions about whether an insurer will cover the cost of treatment, the authors note.
While the report doesn’t provide a consensus definition of clinically meaningful benefit, it does offer a starting point for a conversation about how the phrase should be defined in the context of RCTs for disease-modifying therapies (DMTs) in AD, Dr. Petersen said.
“What we tried to do was to put it into some kind of perspective and at least have people reflect on this: If you’re going to design the perfect drug trial in Alzheimer’s disease, what would it be? We wanted to get people to think about it without digging in their heels for or against,” he added.
The report was published online in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.
A proactive measure
The expert group began its work in January 2022, less than a year after the FDA approved aducanumab. Since the panel began its work, the FDA has approved a second AD drug, lecanemab (Leqembi), and denied accelerated approval of a third medication, donanemab.
“At the time we started this group, we had one approved treatment, and we just knew that there were others on the way, and we needed to be prepared to have this conversation and be more proactive than reactive,” Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association and co-author of the report, said in an interview.
The work group suggests that simply slowing disease progression might be a desired goal for drug trials, especially early on, before cognition and memory are affected.
They also note that a benefit identified during an 18-month clinical trial may ultimately lead to even more meaningful changes over coming years, well beyond the trial’s end.
In addition, the report authors call for the development of better research tools to more accurately assess meaningful change. The Clinical Dementia Rating (CDR) scale is currently the key instrument used as a primary outcome measure in RCTs. However, the report’s authors note that it may not be adequate to measure meaningful change in early-stage disease.
“Developing better tools certainly should be on the radar screen for all of us, because I think we can do better,” Dr. Petersen said. “The CDR, as good as it is and as long as it’s been used in the field, is a pretty blunt instrument, and it’s the result of subjective ratings.”
‘Quality of mind’
Jason Karlawish, MD, professor of medicine, medical ethics, health policy, and neurology at the University of Pennsylvania, Philadelphia, said measuring the actual impact of a drug on a patient’s disease and quality of life has been a hot topic in the AD field for some time, but settling on a definition of “clinically meaningful” that everyone agrees upon will be a challenge.
“I think the idea of ‘clinically meaningful’ is truly a socially constructed idea,” said Dr. Karlawish, co-director of Penn’s Memory Center, who did not work on the report.
“You can come up with objective measures of cognition, but a measure to call something ‘clinically meaningful’ ultimately requires some sort of negotiated social order among clinicians and patients and others who have immediate interest in the health and well-being of the patient.”
Dr. Karlawish added that he’s interested in the conversations the report might prompt and the challenges it could highlight, especially when it comes to how meaningful clinical benefit can be measured, regardless of how it’s defined.
“Hidden in this conversation about clinically meaningful treatments in Alzheimer’s disease is, frankly, not quality of life, but quality of mind,” said Dr. Karlawish. “No measure captures acceptably the very thing that everyone actually cares a lot about and why we view this disease as so dreadful, which is damage to our mind.”
More evidence needed
The development of such tools will take time. What does that mean for drugs already in the pipeline? Members of the work group argue that those trials must move forward at the same time new tools are being created.
“We need to continue to refine, develop better instruments, [and] develop tools that are going to assess the disease in its more subtle features early on, even in the so-called ‘pre-symptomatic’ stage of the disease,” said lead author Dr. Petersen. “We shouldn’t wait for the development of that before intervening if we have a drug that seems to work.”
However, not everyone who agrees with the premise of the report agrees with this position, including Joel S. Perlmutter, MD, professor of neurology, Washington University School of Medicine, St. Louis, who also commented on the report.
As reported by this news organization, Dr. Perlmutter was one of three physicians who resigned from the FDA advisory panel that voted against approving aducanumab after the agency moved forward anyway.
“We have to be careful not to recommend DMTs that we hope will help without strong evidence, especially when potential side effects are not trivial,” Dr. Perlmutter said. “We have to have evidence before making these recommendations so we don’t end up harming people more than helping them.”
The report received no specific funding. Dr. Petersen received consulting fees from Roche, Nestle, Merck, Biogen, Eisai, and Genentech. Full disclosures are included in the original article. Dr. Perlmutter and Dr. Karlawish report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM ALZHEIMER’S AND DEMENTIA
What’s new in brain health?
This transcript has been edited for clarity.
Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany.
Treatment of tension-type headache
I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.
A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.
The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.
In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
Headache after COVID-19
The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.
SSRIs during COVID-19 infection
The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.
Preventing dementia with antihypertensive treatment
The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.
Antiplatelet therapy
The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.
Regular exercise in Parkinson’s disease
The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.
Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.
This transcript has been edited for clarity.
Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany.
Treatment of tension-type headache
I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.
A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.
The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.
In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
Headache after COVID-19
The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.
SSRIs during COVID-19 infection
The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.
Preventing dementia with antihypertensive treatment
The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.
Antiplatelet therapy
The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.
Regular exercise in Parkinson’s disease
The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.
Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.
This transcript has been edited for clarity.
Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany.
Treatment of tension-type headache
I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.
A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.
The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.
In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
Headache after COVID-19
The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.
SSRIs during COVID-19 infection
The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.
Preventing dementia with antihypertensive treatment
The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.
Antiplatelet therapy
The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.
Regular exercise in Parkinson’s disease
The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.
Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.
Be aware of hepatic encephalopathy, dementia overlap in older patients with cirrhosis
, according to a new study involving U.S. veterans.
The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.
“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.
“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.
“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.
The study was published online in The American Journal of Gastroenterology.
Analyzing associations
HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.
Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.
Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.
Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.
In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.
In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.
When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.
“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.
“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
Additional research needed
Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.
“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.
Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.
The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.
Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.
“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”
The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”
Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.
“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”
The study received no financial support. The authors reported no potential competing interests.
A version of this article first appeared on Medscape.com.
, according to a new study involving U.S. veterans.
The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.
“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.
“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.
“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.
The study was published online in The American Journal of Gastroenterology.
Analyzing associations
HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.
Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.
Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.
Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.
In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.
In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.
When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.
“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.
“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
Additional research needed
Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.
“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.
Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.
The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.
Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.
“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”
The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”
Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.
“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”
The study received no financial support. The authors reported no potential competing interests.
A version of this article first appeared on Medscape.com.
, according to a new study involving U.S. veterans.
The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.
“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.
“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.
“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.
The study was published online in The American Journal of Gastroenterology.
Analyzing associations
HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.
Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.
Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.
Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.
In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.
In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.
When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.
“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.
“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
Additional research needed
Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.
“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.
Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.
The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.
Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.
“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”
The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”
Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.
“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”
The study received no financial support. The authors reported no potential competing interests.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY