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Longer telomeres tied to better brain health
, new research suggests.
“This is the largest and most systematic investigation of telomere length and brain structure and function,” said Anya Topiwala, of the University of Oxford (England). “We found that longer telomeres associated with protection against dementia. The links with brain structure, we think, offer a possible mechanism for this protection. The hope is, by understanding the mechanism, new treatment targets could be uncovered,” Dr. Topiwala said.
The study was published online in PLOS ONE.
UK Biobank cohort
Telomeres form protective caps at the ends of chromosomes, and they progressively shorten with age, which may increase susceptibility to age-related diseases including Alzheimer’s disease. The mechanism underlying this risk is unclear and may involve changes in brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized.
Dr. Topiwala and colleagues compared telomere length in white blood cells to brain MRI and health record data in 31,661 middle-aged and older adults in UK Biobank. They found that longer leucocyte telomere length (LTL) was associated with a larger volume of global and subcortical grey matter and a larger hippocampus – both of which shrink in patients with Alzheimer’s disease. Longer telomeres were also associated with a thicker cerebral cortex, which thins as Alzheimer’s disease progresses.
Longer LTL was also associated with reduced incidence of dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.91-0.96).
Dr. Topiwala noted that many of the factors related to telomere shortening, such as age, genetics, and sex, can’t be changed. However, in a previous study, her team found that drinking alcohol may shorten telomere length. “So by this logic, reducing your alcohol intake could curb the shortening,” Dr. Topiwala said.
She said that a limitation of the study is that telomere length was measured in blood rather than brain and that it’s not clear at present how closely the two relate. Also, UK Biobank participants are generally more healthy than is the general population. Also, though telomere length and brain measures were associated, “we cannot from this study prove one is causing the other,” she added.
Need for more research
Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said that it’s been “known for some time that shortened telomeres – the caps at the end of DNA – are associated with increased aging.”
This new study is “interesting,” said Dr. Percy, in that it shows an association between longer telomere length in white blood cells and healthier brain structures in the areas associated with Alzheimer’s disease. The longer telomeres were also associated with lower incidence of all-cause dementia.
But echoing Dr. Topiwala, “association does not mean causation,” Dr. Griffin said. “More research is needed to understand how diverse mechanisms contributing to Alzheimer’s and other dementia can be targeted.”
“The Alzheimer’s Association is accelerating the discovery of novel therapies through its Part the Cloud funding program, which has invested more than $65 million to accelerate the development of 65 drug development programs,” Dr. Griffin said.
The study had no specific funding. Dr. Topiwala and Dr. Griffin report no relevant disclosures.
A version of this article first appeared on Medscape.com.
, new research suggests.
“This is the largest and most systematic investigation of telomere length and brain structure and function,” said Anya Topiwala, of the University of Oxford (England). “We found that longer telomeres associated with protection against dementia. The links with brain structure, we think, offer a possible mechanism for this protection. The hope is, by understanding the mechanism, new treatment targets could be uncovered,” Dr. Topiwala said.
The study was published online in PLOS ONE.
UK Biobank cohort
Telomeres form protective caps at the ends of chromosomes, and they progressively shorten with age, which may increase susceptibility to age-related diseases including Alzheimer’s disease. The mechanism underlying this risk is unclear and may involve changes in brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized.
Dr. Topiwala and colleagues compared telomere length in white blood cells to brain MRI and health record data in 31,661 middle-aged and older adults in UK Biobank. They found that longer leucocyte telomere length (LTL) was associated with a larger volume of global and subcortical grey matter and a larger hippocampus – both of which shrink in patients with Alzheimer’s disease. Longer telomeres were also associated with a thicker cerebral cortex, which thins as Alzheimer’s disease progresses.
Longer LTL was also associated with reduced incidence of dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.91-0.96).
Dr. Topiwala noted that many of the factors related to telomere shortening, such as age, genetics, and sex, can’t be changed. However, in a previous study, her team found that drinking alcohol may shorten telomere length. “So by this logic, reducing your alcohol intake could curb the shortening,” Dr. Topiwala said.
She said that a limitation of the study is that telomere length was measured in blood rather than brain and that it’s not clear at present how closely the two relate. Also, UK Biobank participants are generally more healthy than is the general population. Also, though telomere length and brain measures were associated, “we cannot from this study prove one is causing the other,” she added.
Need for more research
Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said that it’s been “known for some time that shortened telomeres – the caps at the end of DNA – are associated with increased aging.”
This new study is “interesting,” said Dr. Percy, in that it shows an association between longer telomere length in white blood cells and healthier brain structures in the areas associated with Alzheimer’s disease. The longer telomeres were also associated with lower incidence of all-cause dementia.
But echoing Dr. Topiwala, “association does not mean causation,” Dr. Griffin said. “More research is needed to understand how diverse mechanisms contributing to Alzheimer’s and other dementia can be targeted.”
“The Alzheimer’s Association is accelerating the discovery of novel therapies through its Part the Cloud funding program, which has invested more than $65 million to accelerate the development of 65 drug development programs,” Dr. Griffin said.
The study had no specific funding. Dr. Topiwala and Dr. Griffin report no relevant disclosures.
A version of this article first appeared on Medscape.com.
, new research suggests.
“This is the largest and most systematic investigation of telomere length and brain structure and function,” said Anya Topiwala, of the University of Oxford (England). “We found that longer telomeres associated with protection against dementia. The links with brain structure, we think, offer a possible mechanism for this protection. The hope is, by understanding the mechanism, new treatment targets could be uncovered,” Dr. Topiwala said.
The study was published online in PLOS ONE.
UK Biobank cohort
Telomeres form protective caps at the ends of chromosomes, and they progressively shorten with age, which may increase susceptibility to age-related diseases including Alzheimer’s disease. The mechanism underlying this risk is unclear and may involve changes in brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized.
Dr. Topiwala and colleagues compared telomere length in white blood cells to brain MRI and health record data in 31,661 middle-aged and older adults in UK Biobank. They found that longer leucocyte telomere length (LTL) was associated with a larger volume of global and subcortical grey matter and a larger hippocampus – both of which shrink in patients with Alzheimer’s disease. Longer telomeres were also associated with a thicker cerebral cortex, which thins as Alzheimer’s disease progresses.
Longer LTL was also associated with reduced incidence of dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.91-0.96).
Dr. Topiwala noted that many of the factors related to telomere shortening, such as age, genetics, and sex, can’t be changed. However, in a previous study, her team found that drinking alcohol may shorten telomere length. “So by this logic, reducing your alcohol intake could curb the shortening,” Dr. Topiwala said.
She said that a limitation of the study is that telomere length was measured in blood rather than brain and that it’s not clear at present how closely the two relate. Also, UK Biobank participants are generally more healthy than is the general population. Also, though telomere length and brain measures were associated, “we cannot from this study prove one is causing the other,” she added.
Need for more research
Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said that it’s been “known for some time that shortened telomeres – the caps at the end of DNA – are associated with increased aging.”
This new study is “interesting,” said Dr. Percy, in that it shows an association between longer telomere length in white blood cells and healthier brain structures in the areas associated with Alzheimer’s disease. The longer telomeres were also associated with lower incidence of all-cause dementia.
But echoing Dr. Topiwala, “association does not mean causation,” Dr. Griffin said. “More research is needed to understand how diverse mechanisms contributing to Alzheimer’s and other dementia can be targeted.”
“The Alzheimer’s Association is accelerating the discovery of novel therapies through its Part the Cloud funding program, which has invested more than $65 million to accelerate the development of 65 drug development programs,” Dr. Griffin said.
The study had no specific funding. Dr. Topiwala and Dr. Griffin report no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM PLOS ONE
Tooth loss and diabetes together hasten mental decline
most specifically in those 65-74 years of age, new findings suggest.
The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.
“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.
Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”
Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.
The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.
The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.
Diabetes, edentulism, and cognitive decline
The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.
They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.
Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”
The condition of having no teeth is known as edentulism.
The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).
Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).
In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).
Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).
“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
Study limitations: Better data needed
The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.
“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.
Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.
Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”
The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
most specifically in those 65-74 years of age, new findings suggest.
The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.
“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.
Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”
Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.
The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.
The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.
Diabetes, edentulism, and cognitive decline
The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.
They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.
Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”
The condition of having no teeth is known as edentulism.
The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).
Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).
In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).
Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).
“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
Study limitations: Better data needed
The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.
“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.
Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.
Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”
The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
most specifically in those 65-74 years of age, new findings suggest.
The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.
“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.
Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”
Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.
The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.
The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.
Diabetes, edentulism, and cognitive decline
The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.
They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.
Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”
The condition of having no teeth is known as edentulism.
The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).
Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).
In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).
Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).
“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
Study limitations: Better data needed
The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.
“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.
Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.
Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”
The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF DENTAL RESEARCH
Mortality risk in epilepsy: New data
new research shows.
“To our knowledge, this is the only study that has assessed the cause-specific mortality risk among people with epilepsy according to age and disease course,” investigators led by Seo-Young Lee, MD, PhD, of Kangwon National University, Chuncheon, South Korea, write. “Understanding cause-specific mortality risk, particularly the risk of external causes, is important because they are mostly preventable.”
The findings were published online in Neurology.
Higher mortality risk
For the study, researchers analyzed data from the National Health Insurance Service database in Korea from 2006 to 2017 and vital statistics from Statistics Korea from 2008 to 2017.
The study population included 138,998 patients with newly treated epilepsy, with an average at diagnosis of 48.6 years.
Over 665,928 person years of follow-up (mean follow-up, 4.79 years), 20.095 patients died.
People with epilepsy had more than twice the risk for death, compared with the overall population (standardized mortality ratio, 2.25; 95% confidence interval, 2.22-2.28). Mortality was highest in children aged 4 years or younger and was higher in the first year after diagnosis and in women at all age points.
People with epilepsy had a higher mortality risk, compared with the general public, regardless of how many anti-seizure medications they were taking. Those taking only one medication had a 156% higher risk for death (SMR, 1.56; 95% CI, 1.53-1.60), compared with 493% higher risk in those taking four or more medications (SMR, 4.93; 95% CI, 4.76-5.10).
Where patients lived also played a role in mortality risk. Living in a rural area was associated with a 247% higher risk for death, compared with people without epilepsy who lived in the same area (SMR, 2.47; 95% CI, 2.41-2.53), and the risk was 203% higher risk among those living in urban centers (SMR, 2.03; 95% CI, 1.98-2.09).
Although people with comorbidities had higher mortality rates, even those without any other health conditions had a 161% higher risk for death, compared with people without epilepsy (SMR, 1.61; 95% CI, 1.50-1.72).
Causes of death
The most frequent causes of death were malignant neoplasm and cerebrovascular disease, which researchers noted are thought to be underlying causes of epilepsy.
Among external causes of death, suicide was the most common cause (2.6%). The suicide rate was highest among younger patients and gradually decreased with age.
Deaths tied directly to epilepsy, transport accidents, or falls were lower in this study than had been previously reported, which may be due to adequate seizure control or because the number of older people with epilepsy and comorbidities is higher in Korea than that reported in other countries.
“To reduce mortality in people with epilepsy, comprehensive efforts [are needed], including a national policy against stigma of epilepsy and clinicians’ total management such as risk stratification, education about injury prevention, and monitoring for suicidal ideation with psychological intervention, as well as active control of seizures,” the authors write.
Generalizable findings
Joseph Sirven, MD, professor of neurology at Mayo Clinic Florida, Jacksonville, said that although the study included only Korean patients, the findings are applicable to other counties.
That researchers found patients with epilepsy were more than twice as likely to die prematurely, compared with the general population wasn’t particularly surprising, Dr. Sirven said.
“What struck me the most was the fact that even patients who were on a single drug and seemingly well controlled also had excess mortality reported,” Dr. Sirven said. “That these risks occur should be part of what we tell all patients with epilepsy so that they can better arm themselves with information and help to address some of the risks that this study showed.”
Another important finding is the risk for suicide in patients with epilepsy, especially those who are newly diagnosed, he said.
“When we treat a patient with epilepsy, it should not just be about seizures, but we need to inquire about the psychiatric comorbidities and more importantly manage them in a comprehensive manner,” Dr. Sirven said.
The study was funded by Soonchunhyang University Research Fund and the Korea Health Technology R&D Project. The study authors and Dr. Sirven report no relevant financial conflicts.
A version of this article first appeared on Medscape.com.
new research shows.
“To our knowledge, this is the only study that has assessed the cause-specific mortality risk among people with epilepsy according to age and disease course,” investigators led by Seo-Young Lee, MD, PhD, of Kangwon National University, Chuncheon, South Korea, write. “Understanding cause-specific mortality risk, particularly the risk of external causes, is important because they are mostly preventable.”
The findings were published online in Neurology.
Higher mortality risk
For the study, researchers analyzed data from the National Health Insurance Service database in Korea from 2006 to 2017 and vital statistics from Statistics Korea from 2008 to 2017.
The study population included 138,998 patients with newly treated epilepsy, with an average at diagnosis of 48.6 years.
Over 665,928 person years of follow-up (mean follow-up, 4.79 years), 20.095 patients died.
People with epilepsy had more than twice the risk for death, compared with the overall population (standardized mortality ratio, 2.25; 95% confidence interval, 2.22-2.28). Mortality was highest in children aged 4 years or younger and was higher in the first year after diagnosis and in women at all age points.
People with epilepsy had a higher mortality risk, compared with the general public, regardless of how many anti-seizure medications they were taking. Those taking only one medication had a 156% higher risk for death (SMR, 1.56; 95% CI, 1.53-1.60), compared with 493% higher risk in those taking four or more medications (SMR, 4.93; 95% CI, 4.76-5.10).
Where patients lived also played a role in mortality risk. Living in a rural area was associated with a 247% higher risk for death, compared with people without epilepsy who lived in the same area (SMR, 2.47; 95% CI, 2.41-2.53), and the risk was 203% higher risk among those living in urban centers (SMR, 2.03; 95% CI, 1.98-2.09).
Although people with comorbidities had higher mortality rates, even those without any other health conditions had a 161% higher risk for death, compared with people without epilepsy (SMR, 1.61; 95% CI, 1.50-1.72).
Causes of death
The most frequent causes of death were malignant neoplasm and cerebrovascular disease, which researchers noted are thought to be underlying causes of epilepsy.
Among external causes of death, suicide was the most common cause (2.6%). The suicide rate was highest among younger patients and gradually decreased with age.
Deaths tied directly to epilepsy, transport accidents, or falls were lower in this study than had been previously reported, which may be due to adequate seizure control or because the number of older people with epilepsy and comorbidities is higher in Korea than that reported in other countries.
“To reduce mortality in people with epilepsy, comprehensive efforts [are needed], including a national policy against stigma of epilepsy and clinicians’ total management such as risk stratification, education about injury prevention, and monitoring for suicidal ideation with psychological intervention, as well as active control of seizures,” the authors write.
Generalizable findings
Joseph Sirven, MD, professor of neurology at Mayo Clinic Florida, Jacksonville, said that although the study included only Korean patients, the findings are applicable to other counties.
That researchers found patients with epilepsy were more than twice as likely to die prematurely, compared with the general population wasn’t particularly surprising, Dr. Sirven said.
“What struck me the most was the fact that even patients who were on a single drug and seemingly well controlled also had excess mortality reported,” Dr. Sirven said. “That these risks occur should be part of what we tell all patients with epilepsy so that they can better arm themselves with information and help to address some of the risks that this study showed.”
Another important finding is the risk for suicide in patients with epilepsy, especially those who are newly diagnosed, he said.
“When we treat a patient with epilepsy, it should not just be about seizures, but we need to inquire about the psychiatric comorbidities and more importantly manage them in a comprehensive manner,” Dr. Sirven said.
The study was funded by Soonchunhyang University Research Fund and the Korea Health Technology R&D Project. The study authors and Dr. Sirven report no relevant financial conflicts.
A version of this article first appeared on Medscape.com.
new research shows.
“To our knowledge, this is the only study that has assessed the cause-specific mortality risk among people with epilepsy according to age and disease course,” investigators led by Seo-Young Lee, MD, PhD, of Kangwon National University, Chuncheon, South Korea, write. “Understanding cause-specific mortality risk, particularly the risk of external causes, is important because they are mostly preventable.”
The findings were published online in Neurology.
Higher mortality risk
For the study, researchers analyzed data from the National Health Insurance Service database in Korea from 2006 to 2017 and vital statistics from Statistics Korea from 2008 to 2017.
The study population included 138,998 patients with newly treated epilepsy, with an average at diagnosis of 48.6 years.
Over 665,928 person years of follow-up (mean follow-up, 4.79 years), 20.095 patients died.
People with epilepsy had more than twice the risk for death, compared with the overall population (standardized mortality ratio, 2.25; 95% confidence interval, 2.22-2.28). Mortality was highest in children aged 4 years or younger and was higher in the first year after diagnosis and in women at all age points.
People with epilepsy had a higher mortality risk, compared with the general public, regardless of how many anti-seizure medications they were taking. Those taking only one medication had a 156% higher risk for death (SMR, 1.56; 95% CI, 1.53-1.60), compared with 493% higher risk in those taking four or more medications (SMR, 4.93; 95% CI, 4.76-5.10).
Where patients lived also played a role in mortality risk. Living in a rural area was associated with a 247% higher risk for death, compared with people without epilepsy who lived in the same area (SMR, 2.47; 95% CI, 2.41-2.53), and the risk was 203% higher risk among those living in urban centers (SMR, 2.03; 95% CI, 1.98-2.09).
Although people with comorbidities had higher mortality rates, even those without any other health conditions had a 161% higher risk for death, compared with people without epilepsy (SMR, 1.61; 95% CI, 1.50-1.72).
Causes of death
The most frequent causes of death were malignant neoplasm and cerebrovascular disease, which researchers noted are thought to be underlying causes of epilepsy.
Among external causes of death, suicide was the most common cause (2.6%). The suicide rate was highest among younger patients and gradually decreased with age.
Deaths tied directly to epilepsy, transport accidents, or falls were lower in this study than had been previously reported, which may be due to adequate seizure control or because the number of older people with epilepsy and comorbidities is higher in Korea than that reported in other countries.
“To reduce mortality in people with epilepsy, comprehensive efforts [are needed], including a national policy against stigma of epilepsy and clinicians’ total management such as risk stratification, education about injury prevention, and monitoring for suicidal ideation with psychological intervention, as well as active control of seizures,” the authors write.
Generalizable findings
Joseph Sirven, MD, professor of neurology at Mayo Clinic Florida, Jacksonville, said that although the study included only Korean patients, the findings are applicable to other counties.
That researchers found patients with epilepsy were more than twice as likely to die prematurely, compared with the general population wasn’t particularly surprising, Dr. Sirven said.
“What struck me the most was the fact that even patients who were on a single drug and seemingly well controlled also had excess mortality reported,” Dr. Sirven said. “That these risks occur should be part of what we tell all patients with epilepsy so that they can better arm themselves with information and help to address some of the risks that this study showed.”
Another important finding is the risk for suicide in patients with epilepsy, especially those who are newly diagnosed, he said.
“When we treat a patient with epilepsy, it should not just be about seizures, but we need to inquire about the psychiatric comorbidities and more importantly manage them in a comprehensive manner,” Dr. Sirven said.
The study was funded by Soonchunhyang University Research Fund and the Korea Health Technology R&D Project. The study authors and Dr. Sirven report no relevant financial conflicts.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Restless legs a new modifiable risk factor for dementia?
suggesting the disorder may be a risk factor for dementia or a very early noncognitive sign of dementia, researchers say.
In a large population-based cohort study, adults with RLS were significantly more likely to develop dementia over more than a decade than were their peers without RLS.
If confirmed in future studies, “regular check-ups for cognitive decline in older patients with RLS may facilitate earlier detection and intervention for those with dementia risk,” wrote investigators led by Eosu Kim, MD, PhD, with Yonsei University, Seoul, Republic of Korea.
The study was published online in Alzheimer’s Research and Therapy.
Sleep disorders and dementia
RLS is associated with poor sleep, depression/anxiety, poor diet, microvasculopathy, and hypoxia – all of which are known risk factors for dementia. However, the relationship between RLS and incident dementia has been unclear.
The researchers compared risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) among 2,501 adults with newly diagnosed RLS and 9,977 matched control persons participating in the Korean National Health Insurance Service–Elderly Cohort, a nationwide population-based cohort of adults aged 60 and older.
The mean age of the cohort was 73 years; most of the participants were women (65%). Among all 12,478 participants, 874 (7%) developed all-cause dementia during follow-up – 475 (54%) developed AD, and 194 (22%) developed VaD.
The incidence of all-cause dementia was significantly higher among the RLS group than among the control group (10.4% vs. 6.2%). Incidence rates of AD and VaD (5.6% and 2.6%, respectively) were also higher in the RLS group than in the control group (3.4% and 1.3%, respectively).
In Cox regression analysis, RLS was significantly associated with an increased risk of all-cause dementia (adjusted hazard ratio [aHR], 1.46; 95% confidence interval [CI], 1.24-1.72), AD (aHR 1.38; 95% CI, 1.11-1.72) and VaD (aHR, 1.81; 95% CI, 1.30-2.53).
The researchers noted that RLS may precede deterioration of cognitive function, leading to dementia, and they suggest that RLS could be regarded as a “newly identified” risk factor or prodromal sign of dementia.
Modifiable risk factor
Reached for comment, Thanh Dang-Vu, MD, PhD, professor and research chair in sleep, neuroimaging, and cognitive health at Concordia University in Montreal, said there is now “increasing literature that shows sleep as a modifiable risk factor for cognitive decline.
“Previous evidence indicates that both sleep apnea and insomnia disorder increase the risk for cognitive decline and possibly dementia. Here the study adds to this body of evidence linking sleep disorders to dementia, suggesting that RLS should also be considered as a sleep-related risk factor,” Dr. Dang-Vu told this news organization.
“More evidence is needed, though, as here, all diagnoses were based on national health insurance diagnostic codes, and it is likely there were missed diagnoses for RLS but also for other sleep disorders, as there was no systematic screening for them,” Dr. Dang-Vu cautioned.
Support for the study was provided by the Ministry of Health and Welfare, the Korean government, and Yonsei University. Dr. Kim and Dr. Dang-Vu reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
suggesting the disorder may be a risk factor for dementia or a very early noncognitive sign of dementia, researchers say.
In a large population-based cohort study, adults with RLS were significantly more likely to develop dementia over more than a decade than were their peers without RLS.
If confirmed in future studies, “regular check-ups for cognitive decline in older patients with RLS may facilitate earlier detection and intervention for those with dementia risk,” wrote investigators led by Eosu Kim, MD, PhD, with Yonsei University, Seoul, Republic of Korea.
The study was published online in Alzheimer’s Research and Therapy.
Sleep disorders and dementia
RLS is associated with poor sleep, depression/anxiety, poor diet, microvasculopathy, and hypoxia – all of which are known risk factors for dementia. However, the relationship between RLS and incident dementia has been unclear.
The researchers compared risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) among 2,501 adults with newly diagnosed RLS and 9,977 matched control persons participating in the Korean National Health Insurance Service–Elderly Cohort, a nationwide population-based cohort of adults aged 60 and older.
The mean age of the cohort was 73 years; most of the participants were women (65%). Among all 12,478 participants, 874 (7%) developed all-cause dementia during follow-up – 475 (54%) developed AD, and 194 (22%) developed VaD.
The incidence of all-cause dementia was significantly higher among the RLS group than among the control group (10.4% vs. 6.2%). Incidence rates of AD and VaD (5.6% and 2.6%, respectively) were also higher in the RLS group than in the control group (3.4% and 1.3%, respectively).
In Cox regression analysis, RLS was significantly associated with an increased risk of all-cause dementia (adjusted hazard ratio [aHR], 1.46; 95% confidence interval [CI], 1.24-1.72), AD (aHR 1.38; 95% CI, 1.11-1.72) and VaD (aHR, 1.81; 95% CI, 1.30-2.53).
The researchers noted that RLS may precede deterioration of cognitive function, leading to dementia, and they suggest that RLS could be regarded as a “newly identified” risk factor or prodromal sign of dementia.
Modifiable risk factor
Reached for comment, Thanh Dang-Vu, MD, PhD, professor and research chair in sleep, neuroimaging, and cognitive health at Concordia University in Montreal, said there is now “increasing literature that shows sleep as a modifiable risk factor for cognitive decline.
“Previous evidence indicates that both sleep apnea and insomnia disorder increase the risk for cognitive decline and possibly dementia. Here the study adds to this body of evidence linking sleep disorders to dementia, suggesting that RLS should also be considered as a sleep-related risk factor,” Dr. Dang-Vu told this news organization.
“More evidence is needed, though, as here, all diagnoses were based on national health insurance diagnostic codes, and it is likely there were missed diagnoses for RLS but also for other sleep disorders, as there was no systematic screening for them,” Dr. Dang-Vu cautioned.
Support for the study was provided by the Ministry of Health and Welfare, the Korean government, and Yonsei University. Dr. Kim and Dr. Dang-Vu reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
suggesting the disorder may be a risk factor for dementia or a very early noncognitive sign of dementia, researchers say.
In a large population-based cohort study, adults with RLS were significantly more likely to develop dementia over more than a decade than were their peers without RLS.
If confirmed in future studies, “regular check-ups for cognitive decline in older patients with RLS may facilitate earlier detection and intervention for those with dementia risk,” wrote investigators led by Eosu Kim, MD, PhD, with Yonsei University, Seoul, Republic of Korea.
The study was published online in Alzheimer’s Research and Therapy.
Sleep disorders and dementia
RLS is associated with poor sleep, depression/anxiety, poor diet, microvasculopathy, and hypoxia – all of which are known risk factors for dementia. However, the relationship between RLS and incident dementia has been unclear.
The researchers compared risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) among 2,501 adults with newly diagnosed RLS and 9,977 matched control persons participating in the Korean National Health Insurance Service–Elderly Cohort, a nationwide population-based cohort of adults aged 60 and older.
The mean age of the cohort was 73 years; most of the participants were women (65%). Among all 12,478 participants, 874 (7%) developed all-cause dementia during follow-up – 475 (54%) developed AD, and 194 (22%) developed VaD.
The incidence of all-cause dementia was significantly higher among the RLS group than among the control group (10.4% vs. 6.2%). Incidence rates of AD and VaD (5.6% and 2.6%, respectively) were also higher in the RLS group than in the control group (3.4% and 1.3%, respectively).
In Cox regression analysis, RLS was significantly associated with an increased risk of all-cause dementia (adjusted hazard ratio [aHR], 1.46; 95% confidence interval [CI], 1.24-1.72), AD (aHR 1.38; 95% CI, 1.11-1.72) and VaD (aHR, 1.81; 95% CI, 1.30-2.53).
The researchers noted that RLS may precede deterioration of cognitive function, leading to dementia, and they suggest that RLS could be regarded as a “newly identified” risk factor or prodromal sign of dementia.
Modifiable risk factor
Reached for comment, Thanh Dang-Vu, MD, PhD, professor and research chair in sleep, neuroimaging, and cognitive health at Concordia University in Montreal, said there is now “increasing literature that shows sleep as a modifiable risk factor for cognitive decline.
“Previous evidence indicates that both sleep apnea and insomnia disorder increase the risk for cognitive decline and possibly dementia. Here the study adds to this body of evidence linking sleep disorders to dementia, suggesting that RLS should also be considered as a sleep-related risk factor,” Dr. Dang-Vu told this news organization.
“More evidence is needed, though, as here, all diagnoses were based on national health insurance diagnostic codes, and it is likely there were missed diagnoses for RLS but also for other sleep disorders, as there was no systematic screening for them,” Dr. Dang-Vu cautioned.
Support for the study was provided by the Ministry of Health and Welfare, the Korean government, and Yonsei University. Dr. Kim and Dr. Dang-Vu reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ALZHEIMER’S RESEARCH AND THERAPY
What’s driving the "world’s fastest-growing brain disease"?
An international team of researchers reviewed previous research and cited data that suggest the chemical trichloroethylene (TCE) is associated with as much as a 500% increased risk for Parkinson’s disease (PD).
Lead investigator Ray Dorsey, MD, professor of neurology, University of Rochester, N.Y., called PD “the world’s fastest-growing brain disease,” and told this news organization that it “may be largely preventable.”
“Countless people have died over generations from cancer and other disease linked to TCE [and] Parkinson’s may be the latest,” he said. “Banning these chemicals, containing contaminated sites, and protecting homes, schools, and buildings at risk may all create a world where Parkinson’s is increasingly rare, not common.”
The paper was published online in the Journal of Parkinson’s Disease.
Invisible, ubiquitous
TCE was first synthesized in a lab in 1864, with commercial production beginning in 1920, the researchers noted.
“Because of its unique properties, TCE has had countless industrial, commercial, military, and medical applications,” including producing refrigerants, cleaning electronics, and degreasing engine parts.
In addition, it’s been used in dry cleaning, although a similar chemical (perchloroethylene [PCE]) is currently more widely used for that purpose. Nevertheless, the authors noted, in anaerobic conditions, perchloroethylene often transforms into TCE “and their toxicity may be similar.”
Consumer products in which TCE is found include typewriter correction fluid, paint removers, gun cleaners, and aerosol cleaning products. Up until the 1970s, it was used to decaffeinate coffee.
TCE exposure isn’t confined to those who work with it. It also pollutes outdoor air, taints groundwater, and contaminates indoor air. It’s present in a substantial amount of groundwater in the United States and it “evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected,” the researchers noted.
“Exposure can come via occupation or the environment and is often largely unknown at the time it occurs,” Dr. Dorsey said.
He noted that the rapid increase in PD incidence cannot be explained by genetic factors alone, which affect only about 15% of patients with PD, nor can it be explained by aging alone. “Certain pesticides ... are likely causes but would not explain the high prevalence of PD in urban areas, as is the case in the U.S.” Rather, “other factors” are involved, and “TCE is likely one such factor.”
Yet, “despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited.”
To fill this knowledge gap, Dr. Dorsey and his coauthors of the book, “Ending Parkinson’s Disease: A Prescription for Action,” took a deep dive into studies focusing on the potential association of TCE and PD and presented seven cases to illustrate the association.
“Like many genetic mutations (e.g., Parkin) and other environmental toxicants ... TCE damages the energy-producing parts of cells, i.e., the mitochondria,” said Dr. Dorsey.
TCE and PCE “likely mediate their toxicity through a common metabolite.” Because both are lipophilic, they “readily distribute in the brain and body tissues and appear to cause mitochondrial dysfunction at high doses,” the researchers hypothesized.
Dopaminergic neurons are particularly sensitive to mitochondrial neurotoxicants, so this might “partially explain the link to PD.”
Animal studies have shown that TCE “caused selective loss of dopaminergic neurons.” Moreover, PD-related neuropathology was found in the substantia nigra of rodents exposed to TCE over time. In addition, studies as early as 1960 were showing an association between TCE and parkinsonism.
The authors describe TCE as “ubiquitous” in the 1970s, with 10 million Americans working with the chemical or other organic solvents daily. The review details an extensive list of industries and occupations in which TCE exposure continues to occur.
People working with TCE might inhale it or touch it; but “millions more encounter the chemical unknowingly through outdoor air, contaminated groundwater, and indoor air pollution.”
They noted that TCE contaminates up to one-third of U.S. drinking water, has polluted the groundwater in more than 20 different countries on five continents, and is found in half of the 1,300 most toxic “Superfund” sites that are “part of a federal clean-up program, including 15 in California’s Silicon Valley, where TCE was used to clean electronics.”
Although the U.S. military stopped using TCE, numerous sites have been contaminated, including Marine Corps Base Camp Lejeune in North Carolina, where TCE and PCE were found in drinking water at 280 times the recommended safety standards.
The researchers highlighted seven cases of individuals who developed PD after likely exposure to TCE, including NBA basketball player Brian Grant, who developed symptoms of PD in 2006 at the age of 34.
Mr. Grant and his family had lived in Camp Lejeune when he was a child, during which time he drank, bathed, and swam in contaminated water, “unaware of its toxicity.” His father also died of esophageal cancer, “which is linked to TCE,” the authors of the study wrote. Mr. Grant has created a foundation to inspire and support patients with PD.
All of the individuals either grew up in or spent time in an area where they were extensively exposed to TCE, PCE, or other chemicals, or experienced occupational exposure.
The authors acknowledged that the role of TCE in PD, as illustrated by the cases, is “far from definitive.” For example, exposure to TCE is often combined with exposure to other toxins, or with unmeasured genetic risk factors.
They highlighted the need for more research and called for cleaning and containing contaminated sites, monitoring TCE levels, and publicly communicating risk and a ban on TCE.
Recall bias?
Commenting for this news organization, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association (APDA), noted that the authors “are very frank about the limitations of this approach [illustrative cases] as proof of causation between PD and TCE exposure.”
Another limitation is that TCE exposure is very common, “as argued in the paper.” But “most people with exposure do not develop PD,” Dr. Gilbert pointed out. “By probing the TCE exposure of those who already have PD, there is a danger of recall bias.”
Dr. Gilbert, associate professor of neurology at NYU Langone Health, who was not involved with the study, acknowledged that the authors “present their work as hypothesis and clearly state that more work is needed to understand the connection between TCE and PD.”
In the meantime, however, there are “well-established health risks of TCE exposure, including development of various cancers,” she said. Therefore, the authors’ goals appear to be educating the public about known health risks, working to clean up known sites of contamination, and advocating to ban future use of TCE.
These goals “do not need to wait for [proof of] firm causation between TCE and PD,” she stated.
Dr. Dorsey reported he has received honoraria for speaking at the American Academy of Neurology and at multiple other societies and foundations and has received compensation for consulting services from pharmaceutical companies, foundations, medical education companies, and medical publications; he owns stock in several companies. The other authors’ disclosures can be found in the original paper. Dr. Gilbert is employed by the American Parkinson Disease Association and Bellevue Hospital Center in New York City.
A version of this article first appeared on Medscape.com.
An international team of researchers reviewed previous research and cited data that suggest the chemical trichloroethylene (TCE) is associated with as much as a 500% increased risk for Parkinson’s disease (PD).
Lead investigator Ray Dorsey, MD, professor of neurology, University of Rochester, N.Y., called PD “the world’s fastest-growing brain disease,” and told this news organization that it “may be largely preventable.”
“Countless people have died over generations from cancer and other disease linked to TCE [and] Parkinson’s may be the latest,” he said. “Banning these chemicals, containing contaminated sites, and protecting homes, schools, and buildings at risk may all create a world where Parkinson’s is increasingly rare, not common.”
The paper was published online in the Journal of Parkinson’s Disease.
Invisible, ubiquitous
TCE was first synthesized in a lab in 1864, with commercial production beginning in 1920, the researchers noted.
“Because of its unique properties, TCE has had countless industrial, commercial, military, and medical applications,” including producing refrigerants, cleaning electronics, and degreasing engine parts.
In addition, it’s been used in dry cleaning, although a similar chemical (perchloroethylene [PCE]) is currently more widely used for that purpose. Nevertheless, the authors noted, in anaerobic conditions, perchloroethylene often transforms into TCE “and their toxicity may be similar.”
Consumer products in which TCE is found include typewriter correction fluid, paint removers, gun cleaners, and aerosol cleaning products. Up until the 1970s, it was used to decaffeinate coffee.
TCE exposure isn’t confined to those who work with it. It also pollutes outdoor air, taints groundwater, and contaminates indoor air. It’s present in a substantial amount of groundwater in the United States and it “evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected,” the researchers noted.
“Exposure can come via occupation or the environment and is often largely unknown at the time it occurs,” Dr. Dorsey said.
He noted that the rapid increase in PD incidence cannot be explained by genetic factors alone, which affect only about 15% of patients with PD, nor can it be explained by aging alone. “Certain pesticides ... are likely causes but would not explain the high prevalence of PD in urban areas, as is the case in the U.S.” Rather, “other factors” are involved, and “TCE is likely one such factor.”
Yet, “despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited.”
To fill this knowledge gap, Dr. Dorsey and his coauthors of the book, “Ending Parkinson’s Disease: A Prescription for Action,” took a deep dive into studies focusing on the potential association of TCE and PD and presented seven cases to illustrate the association.
“Like many genetic mutations (e.g., Parkin) and other environmental toxicants ... TCE damages the energy-producing parts of cells, i.e., the mitochondria,” said Dr. Dorsey.
TCE and PCE “likely mediate their toxicity through a common metabolite.” Because both are lipophilic, they “readily distribute in the brain and body tissues and appear to cause mitochondrial dysfunction at high doses,” the researchers hypothesized.
Dopaminergic neurons are particularly sensitive to mitochondrial neurotoxicants, so this might “partially explain the link to PD.”
Animal studies have shown that TCE “caused selective loss of dopaminergic neurons.” Moreover, PD-related neuropathology was found in the substantia nigra of rodents exposed to TCE over time. In addition, studies as early as 1960 were showing an association between TCE and parkinsonism.
The authors describe TCE as “ubiquitous” in the 1970s, with 10 million Americans working with the chemical or other organic solvents daily. The review details an extensive list of industries and occupations in which TCE exposure continues to occur.
People working with TCE might inhale it or touch it; but “millions more encounter the chemical unknowingly through outdoor air, contaminated groundwater, and indoor air pollution.”
They noted that TCE contaminates up to one-third of U.S. drinking water, has polluted the groundwater in more than 20 different countries on five continents, and is found in half of the 1,300 most toxic “Superfund” sites that are “part of a federal clean-up program, including 15 in California’s Silicon Valley, where TCE was used to clean electronics.”
Although the U.S. military stopped using TCE, numerous sites have been contaminated, including Marine Corps Base Camp Lejeune in North Carolina, where TCE and PCE were found in drinking water at 280 times the recommended safety standards.
The researchers highlighted seven cases of individuals who developed PD after likely exposure to TCE, including NBA basketball player Brian Grant, who developed symptoms of PD in 2006 at the age of 34.
Mr. Grant and his family had lived in Camp Lejeune when he was a child, during which time he drank, bathed, and swam in contaminated water, “unaware of its toxicity.” His father also died of esophageal cancer, “which is linked to TCE,” the authors of the study wrote. Mr. Grant has created a foundation to inspire and support patients with PD.
All of the individuals either grew up in or spent time in an area where they were extensively exposed to TCE, PCE, or other chemicals, or experienced occupational exposure.
The authors acknowledged that the role of TCE in PD, as illustrated by the cases, is “far from definitive.” For example, exposure to TCE is often combined with exposure to other toxins, or with unmeasured genetic risk factors.
They highlighted the need for more research and called for cleaning and containing contaminated sites, monitoring TCE levels, and publicly communicating risk and a ban on TCE.
Recall bias?
Commenting for this news organization, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association (APDA), noted that the authors “are very frank about the limitations of this approach [illustrative cases] as proof of causation between PD and TCE exposure.”
Another limitation is that TCE exposure is very common, “as argued in the paper.” But “most people with exposure do not develop PD,” Dr. Gilbert pointed out. “By probing the TCE exposure of those who already have PD, there is a danger of recall bias.”
Dr. Gilbert, associate professor of neurology at NYU Langone Health, who was not involved with the study, acknowledged that the authors “present their work as hypothesis and clearly state that more work is needed to understand the connection between TCE and PD.”
In the meantime, however, there are “well-established health risks of TCE exposure, including development of various cancers,” she said. Therefore, the authors’ goals appear to be educating the public about known health risks, working to clean up known sites of contamination, and advocating to ban future use of TCE.
These goals “do not need to wait for [proof of] firm causation between TCE and PD,” she stated.
Dr. Dorsey reported he has received honoraria for speaking at the American Academy of Neurology and at multiple other societies and foundations and has received compensation for consulting services from pharmaceutical companies, foundations, medical education companies, and medical publications; he owns stock in several companies. The other authors’ disclosures can be found in the original paper. Dr. Gilbert is employed by the American Parkinson Disease Association and Bellevue Hospital Center in New York City.
A version of this article first appeared on Medscape.com.
An international team of researchers reviewed previous research and cited data that suggest the chemical trichloroethylene (TCE) is associated with as much as a 500% increased risk for Parkinson’s disease (PD).
Lead investigator Ray Dorsey, MD, professor of neurology, University of Rochester, N.Y., called PD “the world’s fastest-growing brain disease,” and told this news organization that it “may be largely preventable.”
“Countless people have died over generations from cancer and other disease linked to TCE [and] Parkinson’s may be the latest,” he said. “Banning these chemicals, containing contaminated sites, and protecting homes, schools, and buildings at risk may all create a world where Parkinson’s is increasingly rare, not common.”
The paper was published online in the Journal of Parkinson’s Disease.
Invisible, ubiquitous
TCE was first synthesized in a lab in 1864, with commercial production beginning in 1920, the researchers noted.
“Because of its unique properties, TCE has had countless industrial, commercial, military, and medical applications,” including producing refrigerants, cleaning electronics, and degreasing engine parts.
In addition, it’s been used in dry cleaning, although a similar chemical (perchloroethylene [PCE]) is currently more widely used for that purpose. Nevertheless, the authors noted, in anaerobic conditions, perchloroethylene often transforms into TCE “and their toxicity may be similar.”
Consumer products in which TCE is found include typewriter correction fluid, paint removers, gun cleaners, and aerosol cleaning products. Up until the 1970s, it was used to decaffeinate coffee.
TCE exposure isn’t confined to those who work with it. It also pollutes outdoor air, taints groundwater, and contaminates indoor air. It’s present in a substantial amount of groundwater in the United States and it “evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected,” the researchers noted.
“Exposure can come via occupation or the environment and is often largely unknown at the time it occurs,” Dr. Dorsey said.
He noted that the rapid increase in PD incidence cannot be explained by genetic factors alone, which affect only about 15% of patients with PD, nor can it be explained by aging alone. “Certain pesticides ... are likely causes but would not explain the high prevalence of PD in urban areas, as is the case in the U.S.” Rather, “other factors” are involved, and “TCE is likely one such factor.”
Yet, “despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited.”
To fill this knowledge gap, Dr. Dorsey and his coauthors of the book, “Ending Parkinson’s Disease: A Prescription for Action,” took a deep dive into studies focusing on the potential association of TCE and PD and presented seven cases to illustrate the association.
“Like many genetic mutations (e.g., Parkin) and other environmental toxicants ... TCE damages the energy-producing parts of cells, i.e., the mitochondria,” said Dr. Dorsey.
TCE and PCE “likely mediate their toxicity through a common metabolite.” Because both are lipophilic, they “readily distribute in the brain and body tissues and appear to cause mitochondrial dysfunction at high doses,” the researchers hypothesized.
Dopaminergic neurons are particularly sensitive to mitochondrial neurotoxicants, so this might “partially explain the link to PD.”
Animal studies have shown that TCE “caused selective loss of dopaminergic neurons.” Moreover, PD-related neuropathology was found in the substantia nigra of rodents exposed to TCE over time. In addition, studies as early as 1960 were showing an association between TCE and parkinsonism.
The authors describe TCE as “ubiquitous” in the 1970s, with 10 million Americans working with the chemical or other organic solvents daily. The review details an extensive list of industries and occupations in which TCE exposure continues to occur.
People working with TCE might inhale it or touch it; but “millions more encounter the chemical unknowingly through outdoor air, contaminated groundwater, and indoor air pollution.”
They noted that TCE contaminates up to one-third of U.S. drinking water, has polluted the groundwater in more than 20 different countries on five continents, and is found in half of the 1,300 most toxic “Superfund” sites that are “part of a federal clean-up program, including 15 in California’s Silicon Valley, where TCE was used to clean electronics.”
Although the U.S. military stopped using TCE, numerous sites have been contaminated, including Marine Corps Base Camp Lejeune in North Carolina, where TCE and PCE were found in drinking water at 280 times the recommended safety standards.
The researchers highlighted seven cases of individuals who developed PD after likely exposure to TCE, including NBA basketball player Brian Grant, who developed symptoms of PD in 2006 at the age of 34.
Mr. Grant and his family had lived in Camp Lejeune when he was a child, during which time he drank, bathed, and swam in contaminated water, “unaware of its toxicity.” His father also died of esophageal cancer, “which is linked to TCE,” the authors of the study wrote. Mr. Grant has created a foundation to inspire and support patients with PD.
All of the individuals either grew up in or spent time in an area where they were extensively exposed to TCE, PCE, or other chemicals, or experienced occupational exposure.
The authors acknowledged that the role of TCE in PD, as illustrated by the cases, is “far from definitive.” For example, exposure to TCE is often combined with exposure to other toxins, or with unmeasured genetic risk factors.
They highlighted the need for more research and called for cleaning and containing contaminated sites, monitoring TCE levels, and publicly communicating risk and a ban on TCE.
Recall bias?
Commenting for this news organization, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association (APDA), noted that the authors “are very frank about the limitations of this approach [illustrative cases] as proof of causation between PD and TCE exposure.”
Another limitation is that TCE exposure is very common, “as argued in the paper.” But “most people with exposure do not develop PD,” Dr. Gilbert pointed out. “By probing the TCE exposure of those who already have PD, there is a danger of recall bias.”
Dr. Gilbert, associate professor of neurology at NYU Langone Health, who was not involved with the study, acknowledged that the authors “present their work as hypothesis and clearly state that more work is needed to understand the connection between TCE and PD.”
In the meantime, however, there are “well-established health risks of TCE exposure, including development of various cancers,” she said. Therefore, the authors’ goals appear to be educating the public about known health risks, working to clean up known sites of contamination, and advocating to ban future use of TCE.
These goals “do not need to wait for [proof of] firm causation between TCE and PD,” she stated.
Dr. Dorsey reported he has received honoraria for speaking at the American Academy of Neurology and at multiple other societies and foundations and has received compensation for consulting services from pharmaceutical companies, foundations, medical education companies, and medical publications; he owns stock in several companies. The other authors’ disclosures can be found in the original paper. Dr. Gilbert is employed by the American Parkinson Disease Association and Bellevue Hospital Center in New York City.
A version of this article first appeared on Medscape.com.
FROM JOURNAL OF PARKINSON’S DISEASE
High caffeine levels may lower body fat, type 2 diabetes risks
the results of a new study suggest.
Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.
In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.
The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”
Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.
The work was published online March 14 in BMJ Medicine.
“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.
“It does not, however, prove cause and effect.”
The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”
Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”
“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.
Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.
Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m2 in BMI (P < .001).
For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).
Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).
Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).
Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.
They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).
The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.
“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”
The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
the results of a new study suggest.
Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.
In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.
The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”
Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.
The work was published online March 14 in BMJ Medicine.
“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.
“It does not, however, prove cause and effect.”
The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”
Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”
“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.
Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.
Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m2 in BMI (P < .001).
For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).
Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).
Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).
Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.
They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).
The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.
“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”
The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
the results of a new study suggest.
Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.
In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.
The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”
Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.
The work was published online March 14 in BMJ Medicine.
“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.
“It does not, however, prove cause and effect.”
The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”
Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”
“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.
Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.
Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m2 in BMI (P < .001).
For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).
Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).
Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).
Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.
They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).
The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.
“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”
The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM BMJ MEDICINE
Two diets tied to lower Alzheimer’s pathology at autopsy
In a cohort of deceased older adults, those who had adhered to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) and Mediterranean diets for nearly a decade before death had less global Alzheimer’s disease–related pathology, primarily less beta-amyloid, at autopsy.
Those who most closely followed these diets had almost 40% lower odds of having an Alzheimer’s disease diagnosis at death. The findings offer one mechanism by which healthy diets protect cognition.
“While our research doesn’t prove that a healthy diet resulted in fewer brain deposits of amyloid plaques ... we know there is a relationship, and following the MIND and Mediterranean diets may be one way that people can improve their brain health and protect cognition as they age,” study investigator Puja Agarwal, PhD, of RUSH University Medical Center in Chicago, said in a statement.
The study was published online in Neurology.
Green leafy veggies key
The MIND diet was pioneered by the late Martha Clare Morris, ScD, a Rush nutritional epidemiologist, who died of cancer in 2020 at age 64.
Although similar, the Mediterranean diet recommends vegetables, fruit, and three or more servings of fish per week, whereas the MIND diet prioritizes green leafy vegetables, such as spinach, kale, and collard greens, along with other vegetables. The MIND diet also prioritizes berries over other fruit and recommends one or more servings of fish per week. Both diets recommend small amounts of wine.
The current study focused on 581 older adults who died while participating in the Rush Memory and Aging Project (MAP). All participants agreed to undergo annual clinical evaluations and brain autopsy after death.
Participants completed annual food frequency questionnaires beginning at a mean age of 84. The mean age at death was 91. Mean follow-up was 6.8 years.
Around the time of death, 224 participants (39%) had a diagnosis of clinical dementia, and 383 participants (66%) had a pathologic Alzheimer’s disease diagnosis at time of death.
The researchers used a series of regression analyses to investigate the MIND and Mediterranean diets and dietary components associated with Alzheimer’s disease pathology. They controlled for age at death, sex, education, APO-epsilon 4 status, and total calories.
Overall, both diets were significantly associated with lower global Alzheimer’s disease pathology (MIND: beta = –0.022, P = .034; and Mediterranean: beta = –0.007, P = .039) – specifically, with less beta-amyloid (MIND: beta = –0.068, P = .050; and Mediterranean: beta = –0.040, P = .004).
The findings persisted when the analysis was further adjusted for physical activity, smoking, and vascular disease burden and when participants with mild cognitive impairment or dementia at the baseline dietary assessment were excluded.
Individuals who most closely followed the Mediterranean diet had average beta-amyloid load similar to being 18 years younger than peers with the lowest adherence. And those who most closely followed the MIND diet had average beta-amyloid amounts similar to being 12 years younger than those with the lowest adherence.
A MIND diet score 1 point higher corresponded to typical plaque deposition of participants who are 4.25 years younger in age.
Regarding individual dietary components, those who ate seven or more servings of green leafy vegetables weekly had less global Alzheimer’s disease pathology than peers who ate one or fewer (beta = –0.115, P = .0038). Those who ate seven or more servings per week had plaque amounts in their brains corresponding to being almost 19 years younger in comparison with those who ate the fewest servings per week.
“Our finding that eating more green leafy vegetables is in itself associated with fewer signs of Alzheimer’s disease in the brain is intriguing enough for people to consider adding more of these vegetables to their diet,” Dr. Agarwal said in the news release.
Previous data from the MAP cohort showed that adherence to the MIND diet can improve memory and thinking skills of older adults, even in the presence of Alzheimer’s disease pathology.
Novel study, intriguing results
Heather Snyder, PhD, vice president of medical and scientific relations with the Alzheimer’s Association, noted that a number of studies have linked overall nutrition – especially a balanced diet low in saturated fats and sugar and high in vegetables – with brain health, including cognition, as one ages.
This new study “takes what we know about the link between nutrition and risk for cognitive decline a step further by looking at the specific brain changes that occur in Alzheimer’s disease. The study found an association of certain nutrition behaviors with less of these Alzheimer’s brain changes,” said Dr. Snyder, who was not involved in the study.
“This is intriguing, and more research is needed to test via an intervention if healthy dietary behaviors can modify the presence of Alzheimer’s brain changes and reduce risk of cognitive decline.”
The Alzheimer’s Association is leading a 2-year clinical trial known as US POINTER to study how targeting known dementia risk factors in combination may reduce risk of cognitive decline in older adults. The MIND diet is being used in US POINTER.
“But while we work to find an exact ‘recipe’ for risk reduction, it’s important to eat a heart-healthy diet that incorporates nutrients that our bodies and brains need to be at their best,” Dr. Snyder said.
The study was funded by the National Institutes of Health. Dr. Agarwal and Dr. Snyder have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a cohort of deceased older adults, those who had adhered to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) and Mediterranean diets for nearly a decade before death had less global Alzheimer’s disease–related pathology, primarily less beta-amyloid, at autopsy.
Those who most closely followed these diets had almost 40% lower odds of having an Alzheimer’s disease diagnosis at death. The findings offer one mechanism by which healthy diets protect cognition.
“While our research doesn’t prove that a healthy diet resulted in fewer brain deposits of amyloid plaques ... we know there is a relationship, and following the MIND and Mediterranean diets may be one way that people can improve their brain health and protect cognition as they age,” study investigator Puja Agarwal, PhD, of RUSH University Medical Center in Chicago, said in a statement.
The study was published online in Neurology.
Green leafy veggies key
The MIND diet was pioneered by the late Martha Clare Morris, ScD, a Rush nutritional epidemiologist, who died of cancer in 2020 at age 64.
Although similar, the Mediterranean diet recommends vegetables, fruit, and three or more servings of fish per week, whereas the MIND diet prioritizes green leafy vegetables, such as spinach, kale, and collard greens, along with other vegetables. The MIND diet also prioritizes berries over other fruit and recommends one or more servings of fish per week. Both diets recommend small amounts of wine.
The current study focused on 581 older adults who died while participating in the Rush Memory and Aging Project (MAP). All participants agreed to undergo annual clinical evaluations and brain autopsy after death.
Participants completed annual food frequency questionnaires beginning at a mean age of 84. The mean age at death was 91. Mean follow-up was 6.8 years.
Around the time of death, 224 participants (39%) had a diagnosis of clinical dementia, and 383 participants (66%) had a pathologic Alzheimer’s disease diagnosis at time of death.
The researchers used a series of regression analyses to investigate the MIND and Mediterranean diets and dietary components associated with Alzheimer’s disease pathology. They controlled for age at death, sex, education, APO-epsilon 4 status, and total calories.
Overall, both diets were significantly associated with lower global Alzheimer’s disease pathology (MIND: beta = –0.022, P = .034; and Mediterranean: beta = –0.007, P = .039) – specifically, with less beta-amyloid (MIND: beta = –0.068, P = .050; and Mediterranean: beta = –0.040, P = .004).
The findings persisted when the analysis was further adjusted for physical activity, smoking, and vascular disease burden and when participants with mild cognitive impairment or dementia at the baseline dietary assessment were excluded.
Individuals who most closely followed the Mediterranean diet had average beta-amyloid load similar to being 18 years younger than peers with the lowest adherence. And those who most closely followed the MIND diet had average beta-amyloid amounts similar to being 12 years younger than those with the lowest adherence.
A MIND diet score 1 point higher corresponded to typical plaque deposition of participants who are 4.25 years younger in age.
Regarding individual dietary components, those who ate seven or more servings of green leafy vegetables weekly had less global Alzheimer’s disease pathology than peers who ate one or fewer (beta = –0.115, P = .0038). Those who ate seven or more servings per week had plaque amounts in their brains corresponding to being almost 19 years younger in comparison with those who ate the fewest servings per week.
“Our finding that eating more green leafy vegetables is in itself associated with fewer signs of Alzheimer’s disease in the brain is intriguing enough for people to consider adding more of these vegetables to their diet,” Dr. Agarwal said in the news release.
Previous data from the MAP cohort showed that adherence to the MIND diet can improve memory and thinking skills of older adults, even in the presence of Alzheimer’s disease pathology.
Novel study, intriguing results
Heather Snyder, PhD, vice president of medical and scientific relations with the Alzheimer’s Association, noted that a number of studies have linked overall nutrition – especially a balanced diet low in saturated fats and sugar and high in vegetables – with brain health, including cognition, as one ages.
This new study “takes what we know about the link between nutrition and risk for cognitive decline a step further by looking at the specific brain changes that occur in Alzheimer’s disease. The study found an association of certain nutrition behaviors with less of these Alzheimer’s brain changes,” said Dr. Snyder, who was not involved in the study.
“This is intriguing, and more research is needed to test via an intervention if healthy dietary behaviors can modify the presence of Alzheimer’s brain changes and reduce risk of cognitive decline.”
The Alzheimer’s Association is leading a 2-year clinical trial known as US POINTER to study how targeting known dementia risk factors in combination may reduce risk of cognitive decline in older adults. The MIND diet is being used in US POINTER.
“But while we work to find an exact ‘recipe’ for risk reduction, it’s important to eat a heart-healthy diet that incorporates nutrients that our bodies and brains need to be at their best,” Dr. Snyder said.
The study was funded by the National Institutes of Health. Dr. Agarwal and Dr. Snyder have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a cohort of deceased older adults, those who had adhered to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) and Mediterranean diets for nearly a decade before death had less global Alzheimer’s disease–related pathology, primarily less beta-amyloid, at autopsy.
Those who most closely followed these diets had almost 40% lower odds of having an Alzheimer’s disease diagnosis at death. The findings offer one mechanism by which healthy diets protect cognition.
“While our research doesn’t prove that a healthy diet resulted in fewer brain deposits of amyloid plaques ... we know there is a relationship, and following the MIND and Mediterranean diets may be one way that people can improve their brain health and protect cognition as they age,” study investigator Puja Agarwal, PhD, of RUSH University Medical Center in Chicago, said in a statement.
The study was published online in Neurology.
Green leafy veggies key
The MIND diet was pioneered by the late Martha Clare Morris, ScD, a Rush nutritional epidemiologist, who died of cancer in 2020 at age 64.
Although similar, the Mediterranean diet recommends vegetables, fruit, and three or more servings of fish per week, whereas the MIND diet prioritizes green leafy vegetables, such as spinach, kale, and collard greens, along with other vegetables. The MIND diet also prioritizes berries over other fruit and recommends one or more servings of fish per week. Both diets recommend small amounts of wine.
The current study focused on 581 older adults who died while participating in the Rush Memory and Aging Project (MAP). All participants agreed to undergo annual clinical evaluations and brain autopsy after death.
Participants completed annual food frequency questionnaires beginning at a mean age of 84. The mean age at death was 91. Mean follow-up was 6.8 years.
Around the time of death, 224 participants (39%) had a diagnosis of clinical dementia, and 383 participants (66%) had a pathologic Alzheimer’s disease diagnosis at time of death.
The researchers used a series of regression analyses to investigate the MIND and Mediterranean diets and dietary components associated with Alzheimer’s disease pathology. They controlled for age at death, sex, education, APO-epsilon 4 status, and total calories.
Overall, both diets were significantly associated with lower global Alzheimer’s disease pathology (MIND: beta = –0.022, P = .034; and Mediterranean: beta = –0.007, P = .039) – specifically, with less beta-amyloid (MIND: beta = –0.068, P = .050; and Mediterranean: beta = –0.040, P = .004).
The findings persisted when the analysis was further adjusted for physical activity, smoking, and vascular disease burden and when participants with mild cognitive impairment or dementia at the baseline dietary assessment were excluded.
Individuals who most closely followed the Mediterranean diet had average beta-amyloid load similar to being 18 years younger than peers with the lowest adherence. And those who most closely followed the MIND diet had average beta-amyloid amounts similar to being 12 years younger than those with the lowest adherence.
A MIND diet score 1 point higher corresponded to typical plaque deposition of participants who are 4.25 years younger in age.
Regarding individual dietary components, those who ate seven or more servings of green leafy vegetables weekly had less global Alzheimer’s disease pathology than peers who ate one or fewer (beta = –0.115, P = .0038). Those who ate seven or more servings per week had plaque amounts in their brains corresponding to being almost 19 years younger in comparison with those who ate the fewest servings per week.
“Our finding that eating more green leafy vegetables is in itself associated with fewer signs of Alzheimer’s disease in the brain is intriguing enough for people to consider adding more of these vegetables to their diet,” Dr. Agarwal said in the news release.
Previous data from the MAP cohort showed that adherence to the MIND diet can improve memory and thinking skills of older adults, even in the presence of Alzheimer’s disease pathology.
Novel study, intriguing results
Heather Snyder, PhD, vice president of medical and scientific relations with the Alzheimer’s Association, noted that a number of studies have linked overall nutrition – especially a balanced diet low in saturated fats and sugar and high in vegetables – with brain health, including cognition, as one ages.
This new study “takes what we know about the link between nutrition and risk for cognitive decline a step further by looking at the specific brain changes that occur in Alzheimer’s disease. The study found an association of certain nutrition behaviors with less of these Alzheimer’s brain changes,” said Dr. Snyder, who was not involved in the study.
“This is intriguing, and more research is needed to test via an intervention if healthy dietary behaviors can modify the presence of Alzheimer’s brain changes and reduce risk of cognitive decline.”
The Alzheimer’s Association is leading a 2-year clinical trial known as US POINTER to study how targeting known dementia risk factors in combination may reduce risk of cognitive decline in older adults. The MIND diet is being used in US POINTER.
“But while we work to find an exact ‘recipe’ for risk reduction, it’s important to eat a heart-healthy diet that incorporates nutrients that our bodies and brains need to be at their best,” Dr. Snyder said.
The study was funded by the National Institutes of Health. Dr. Agarwal and Dr. Snyder have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
High stress levels linked to cognitive decline
, a new study shows.
Individuals with elevated stress levels also had higher rates of diabetes, hypertension, and other cardiovascular disease (CVD) risk factors. But even after controlling for those risk factors, stress remained an independent predictor of cognitive decline.
The national cohort study showed that the association between stress and cognition was similar between Black and White individuals and that those with controlled stress were less likely to have cognitive impairment than those with uncontrolled or new stress.
“We have known for a while that excess levels of stress can be harmful for the human body and the heart, but we are now adding more evidence that excess levels of stress can be harmful for cognition,” said lead investigator Ambar Kulshreshtha, MD, PhD, associate professor of family and preventive medicine and epidemiology at Emory University, Atlanta. “We were able to see that regardless of race or gender, stress is bad.”
The findings were published online in JAMA Network Open.
Independent risk factor
For the study, investigators analyzed data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national population-based cohort of Black and White participants aged 45 years or older, sampled from the U.S. population.
Participants completed a questionnaire designed to evaluate stress levels when they were enrolled in the study between 2003 and 2007 and again about 11 years after enrollment.
Of the 24,448 participants (41.6% Black) in the study, 22.9% reported elevated stress levels.
Those with high stress were more likely to be younger, female, Black, smokers, and have a higher body mass index and less likely to have a college degree and to be physically active. They also had a lower family income and were more likely to have cardiovascular disease risk factors, such as hypertension, diabetes, and dyslipidemia.
Participants with elevated levels of perceived stress were 37% more likely to have poor cognition after adjustment for sociodemographic variables, cardiovascular risk factors, and depression (adjusted odds ratio, 1.37; 95% confidence interval, 1.22-1.53).
There was no significant difference between Black and White participants.
Damaging consequences
Researchers also found a dose-response relationship, with the greatest cognitive decline found in people who reported high stress at both time points and those who had new stress at follow up (aOR, 1.16; 95% CI, 0.92-1.45), compared with those with resolved stress (aOR, 1.03; 95% CI, 0.81-1.32) or no stress (aOR, 0.81; 95% CI, 0.68-0.97).
A change in perceived stress by 1 unit was associated with 4% increased risk of cognitive impairment after adjusting for sociodemographic variables, CVD risk factors, lifestyle factors, and depressive symptoms (aOR, 1.04; 95% CI, 1.02-1.06).
Although the study didn’t reveal the mechanisms that might link stress and cognition, it does point to stress as a potentially modifiable risk factor for cognitive decline, Dr. Kulshreshtha said.
“One in three of my patients have had to deal with extra levels of stress and anxiety over the past few years,” said Dr. Kulshreshtha. “We as clinicians are aware that stress can have damaging consequences to the heart and other organs, and when we see patients who have these complaints, especially elderly patients, we should spend some time asking people about their stress and how they are managing it.”
Additional screening
Gregory Day, MD, a neurologist at the Mayo Clinic, Jacksonville, Fla., said that the findings help fill a void in the research about stress and cognition.
“It’s a potentially important association that’s easy for us to miss in clinical practice,” said Dr. Day, who was not a part of the study. “It’s one of those things that we can all recognize impacts health, but we have very few large, well thought out studies that give us the data we need to inform its place in clinical decision-making.”
In addition to its large sample size, the overrepresentation of diverse populations is a strength of the study and a contribution to the field, Dr. Day said.
“One question they don’t directly ask is, is this association maybe due to some differences in stress? And the answer from the paper is probably not, because it looks like when we control for these things, we don’t see big differences incident risk factors between race,” he added.
The findings also point to the need for clinicians, especially primary care physicians, to screen patients for stress during routine examinations.
“Every visit is an opportunity to screen for risk factors that are going to set people up for future brain health,” Dr. Day said. “In addition to screening for all of these other risk factors for brain health, maybe it’s worth including some more global assessment of stress in a standard screener.”
The study was funded by the National Institute of Neurological Disorders and Stroke, the National Institutes of Health, and the National Institute on Aging. Dr. Kulshreshtha and Dr. Day report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new study shows.
Individuals with elevated stress levels also had higher rates of diabetes, hypertension, and other cardiovascular disease (CVD) risk factors. But even after controlling for those risk factors, stress remained an independent predictor of cognitive decline.
The national cohort study showed that the association between stress and cognition was similar between Black and White individuals and that those with controlled stress were less likely to have cognitive impairment than those with uncontrolled or new stress.
“We have known for a while that excess levels of stress can be harmful for the human body and the heart, but we are now adding more evidence that excess levels of stress can be harmful for cognition,” said lead investigator Ambar Kulshreshtha, MD, PhD, associate professor of family and preventive medicine and epidemiology at Emory University, Atlanta. “We were able to see that regardless of race or gender, stress is bad.”
The findings were published online in JAMA Network Open.
Independent risk factor
For the study, investigators analyzed data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national population-based cohort of Black and White participants aged 45 years or older, sampled from the U.S. population.
Participants completed a questionnaire designed to evaluate stress levels when they were enrolled in the study between 2003 and 2007 and again about 11 years after enrollment.
Of the 24,448 participants (41.6% Black) in the study, 22.9% reported elevated stress levels.
Those with high stress were more likely to be younger, female, Black, smokers, and have a higher body mass index and less likely to have a college degree and to be physically active. They also had a lower family income and were more likely to have cardiovascular disease risk factors, such as hypertension, diabetes, and dyslipidemia.
Participants with elevated levels of perceived stress were 37% more likely to have poor cognition after adjustment for sociodemographic variables, cardiovascular risk factors, and depression (adjusted odds ratio, 1.37; 95% confidence interval, 1.22-1.53).
There was no significant difference between Black and White participants.
Damaging consequences
Researchers also found a dose-response relationship, with the greatest cognitive decline found in people who reported high stress at both time points and those who had new stress at follow up (aOR, 1.16; 95% CI, 0.92-1.45), compared with those with resolved stress (aOR, 1.03; 95% CI, 0.81-1.32) or no stress (aOR, 0.81; 95% CI, 0.68-0.97).
A change in perceived stress by 1 unit was associated with 4% increased risk of cognitive impairment after adjusting for sociodemographic variables, CVD risk factors, lifestyle factors, and depressive symptoms (aOR, 1.04; 95% CI, 1.02-1.06).
Although the study didn’t reveal the mechanisms that might link stress and cognition, it does point to stress as a potentially modifiable risk factor for cognitive decline, Dr. Kulshreshtha said.
“One in three of my patients have had to deal with extra levels of stress and anxiety over the past few years,” said Dr. Kulshreshtha. “We as clinicians are aware that stress can have damaging consequences to the heart and other organs, and when we see patients who have these complaints, especially elderly patients, we should spend some time asking people about their stress and how they are managing it.”
Additional screening
Gregory Day, MD, a neurologist at the Mayo Clinic, Jacksonville, Fla., said that the findings help fill a void in the research about stress and cognition.
“It’s a potentially important association that’s easy for us to miss in clinical practice,” said Dr. Day, who was not a part of the study. “It’s one of those things that we can all recognize impacts health, but we have very few large, well thought out studies that give us the data we need to inform its place in clinical decision-making.”
In addition to its large sample size, the overrepresentation of diverse populations is a strength of the study and a contribution to the field, Dr. Day said.
“One question they don’t directly ask is, is this association maybe due to some differences in stress? And the answer from the paper is probably not, because it looks like when we control for these things, we don’t see big differences incident risk factors between race,” he added.
The findings also point to the need for clinicians, especially primary care physicians, to screen patients for stress during routine examinations.
“Every visit is an opportunity to screen for risk factors that are going to set people up for future brain health,” Dr. Day said. “In addition to screening for all of these other risk factors for brain health, maybe it’s worth including some more global assessment of stress in a standard screener.”
The study was funded by the National Institute of Neurological Disorders and Stroke, the National Institutes of Health, and the National Institute on Aging. Dr. Kulshreshtha and Dr. Day report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new study shows.
Individuals with elevated stress levels also had higher rates of diabetes, hypertension, and other cardiovascular disease (CVD) risk factors. But even after controlling for those risk factors, stress remained an independent predictor of cognitive decline.
The national cohort study showed that the association between stress and cognition was similar between Black and White individuals and that those with controlled stress were less likely to have cognitive impairment than those with uncontrolled or new stress.
“We have known for a while that excess levels of stress can be harmful for the human body and the heart, but we are now adding more evidence that excess levels of stress can be harmful for cognition,” said lead investigator Ambar Kulshreshtha, MD, PhD, associate professor of family and preventive medicine and epidemiology at Emory University, Atlanta. “We were able to see that regardless of race or gender, stress is bad.”
The findings were published online in JAMA Network Open.
Independent risk factor
For the study, investigators analyzed data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national population-based cohort of Black and White participants aged 45 years or older, sampled from the U.S. population.
Participants completed a questionnaire designed to evaluate stress levels when they were enrolled in the study between 2003 and 2007 and again about 11 years after enrollment.
Of the 24,448 participants (41.6% Black) in the study, 22.9% reported elevated stress levels.
Those with high stress were more likely to be younger, female, Black, smokers, and have a higher body mass index and less likely to have a college degree and to be physically active. They also had a lower family income and were more likely to have cardiovascular disease risk factors, such as hypertension, diabetes, and dyslipidemia.
Participants with elevated levels of perceived stress were 37% more likely to have poor cognition after adjustment for sociodemographic variables, cardiovascular risk factors, and depression (adjusted odds ratio, 1.37; 95% confidence interval, 1.22-1.53).
There was no significant difference between Black and White participants.
Damaging consequences
Researchers also found a dose-response relationship, with the greatest cognitive decline found in people who reported high stress at both time points and those who had new stress at follow up (aOR, 1.16; 95% CI, 0.92-1.45), compared with those with resolved stress (aOR, 1.03; 95% CI, 0.81-1.32) or no stress (aOR, 0.81; 95% CI, 0.68-0.97).
A change in perceived stress by 1 unit was associated with 4% increased risk of cognitive impairment after adjusting for sociodemographic variables, CVD risk factors, lifestyle factors, and depressive symptoms (aOR, 1.04; 95% CI, 1.02-1.06).
Although the study didn’t reveal the mechanisms that might link stress and cognition, it does point to stress as a potentially modifiable risk factor for cognitive decline, Dr. Kulshreshtha said.
“One in three of my patients have had to deal with extra levels of stress and anxiety over the past few years,” said Dr. Kulshreshtha. “We as clinicians are aware that stress can have damaging consequences to the heart and other organs, and when we see patients who have these complaints, especially elderly patients, we should spend some time asking people about their stress and how they are managing it.”
Additional screening
Gregory Day, MD, a neurologist at the Mayo Clinic, Jacksonville, Fla., said that the findings help fill a void in the research about stress and cognition.
“It’s a potentially important association that’s easy for us to miss in clinical practice,” said Dr. Day, who was not a part of the study. “It’s one of those things that we can all recognize impacts health, but we have very few large, well thought out studies that give us the data we need to inform its place in clinical decision-making.”
In addition to its large sample size, the overrepresentation of diverse populations is a strength of the study and a contribution to the field, Dr. Day said.
“One question they don’t directly ask is, is this association maybe due to some differences in stress? And the answer from the paper is probably not, because it looks like when we control for these things, we don’t see big differences incident risk factors between race,” he added.
The findings also point to the need for clinicians, especially primary care physicians, to screen patients for stress during routine examinations.
“Every visit is an opportunity to screen for risk factors that are going to set people up for future brain health,” Dr. Day said. “In addition to screening for all of these other risk factors for brain health, maybe it’s worth including some more global assessment of stress in a standard screener.”
The study was funded by the National Institute of Neurological Disorders and Stroke, the National Institutes of Health, and the National Institute on Aging. Dr. Kulshreshtha and Dr. Day report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From JAMA Network Open
Once-daily stimulant for ADHD safe, effective at 1 year
new research shows.
Results from a phase 3, multicenter, dose-optimization, open-label safety study of Azstarys (KemPharm) found that most treatment-emergent adverse events (TEAEs) were mild to moderate.
“This data show that Azstarys remains safe and effective for the treatment of ADHD when given for up to a year,” lead investigator Ann Childress, MD, president of the Center for Psychiatry and Behavioral Medicine, Las Vegas, said in an interview.
The study was published online in the Journal of Child and Adolescent Psychopharmacology.
Safety at 1 year
The drug is a combination of extended-release serdexmethylphenidate (SDX), KemPharm’s prodrug of dexmethylphenidate, coformulated with immediate-release d-MPH.
SDX is converted to d-MPH after it is absorbed in the gastrointestinal tract. The d-MPH is released gradually throughout the day, providing quick symptom control with the d-MPH and extended control with SDX.
Azstarys was approved by the Food and Drug Administration in 2021 on the basis of results from a laboratory classroom phase 3 trial, which showed significant improvement in ADHD symptoms, compared with placebo.
For this study, the second phase 3 trial of Azstarys, investigators analyzed data from 282 children aged 6-12 years in the United States, including 70 who participated in an earlier 1-month efficacy trial.
After screening and a 3-week dose-optimization phase for new participants, patients received once-daily treatment with doses of 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, or 52.3 mg/10.4 mg of SDX/d-MPH.
After 1 year of treatment, 60.1% of participants reported at least one TEAE, the majority of which were moderate. Twelve patients reported severe TEAEs. Six children (2.5%) discontinued the study because of a TEAE during the treatment phase.
The investigators also measured growth and changes in sleep with the Children’s Sleep Habits Questionnaire during the 12-month study. Sleep improved on most measures and the impact on growth was mild.
There were no life-threatening TEAEs and no deaths reported during the study.
The most common TEAEs during the treatment phase were decreased appetite, upper respiratory tract infection, nasopharyngitis, decreased weight, irritability, and increased weight.
Efficacy at 1 year
ADHD symptoms improved considerably after 1 month of treatment, with responses continuing at 1 year.
At baseline, participants’ mean ADHD Rating Scale–5 score was 41.5. After 1 month of treatment, scores averaged 16.1, a decline of –25.3 (P < .001).
The mean score stabilized in the 12-15 range for the remainder of the study. After 1 year of treatment, ADHD symptoms had decreased approximately 70% from baseline.
Investigators found similar results in clinical severity. After 1 month of treatment, the average Clinical Global Impressions–Severity (CGI-S) scale score was 2.5, a decline of –2.2 (P < .0001).
CGI-S scale scores remained in the 2.2-2.4 range for the remainder of the study.
These results, combined with the results of the original classroom trial, suggest Azstarys may offer advantages over other ADHD drugs, Dr. Childress said.
“In the laboratory classroom trial, subjects taking Azstarys completed significantly more math problems than subjects taking placebo beginning at 30 minutes and up to 13 hours after dosing,” Dr. Childress said. “No other methylphenidate extended-release product currently marketed in the United States has a 13-hour duration of effect.”
‘Reassuring data’
Commenting on the findings, Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, said that the study suggests the drug may be a valuable addition to ADHD treatment options for pediatric patients.
“The study provides reassuring data on the safety of stimulants in patients without significant history of cardiac events or blood pressure changes, which are usual concerns among patients and clinicians despite the evidence supporting safety, said Dr. Pawar, who was not part of the study.
“Additionally, the 1-year data on efficacy and safety of a new stimulant medication is valuable for clinicians looking for sustained relief for their patients, despite the limitations of an open-label trial,” she added.
Overall, the safety data reported in the study are fairly consistent with the safety profile of other methylphenidates used for treating ADHD, Dr. Pawar said.
However, she noted, the study does have some limitations, including its open-label design and lack of blinding. The research also excluded children with autism, disruptive mood dysregulation disorders, and other common comorbidities of ADHD, which may limit the generalizability of the results.
“These comorbidities often require stimulants as a part of treatment, and yet have a higher risk of side effects,” Dr. Pawar said. “Future studies with a broader population may be needed to better understand treatment effectiveness and potential risks.”
The study was funded by KemPharm. Dr. Childress serves as consultant for Aardvark, Arbor, Attentive, Cingulate, Ironshore, Neos Therapeutics, Neurocentria, Otsuka, Purdue, Rhodes, Sunovion, Tris Pharma, KemPharm, Supernus, Jazz, Corium, Tulex, and Lumos.
A version of this article first appeared on Medscape.com.
new research shows.
Results from a phase 3, multicenter, dose-optimization, open-label safety study of Azstarys (KemPharm) found that most treatment-emergent adverse events (TEAEs) were mild to moderate.
“This data show that Azstarys remains safe and effective for the treatment of ADHD when given for up to a year,” lead investigator Ann Childress, MD, president of the Center for Psychiatry and Behavioral Medicine, Las Vegas, said in an interview.
The study was published online in the Journal of Child and Adolescent Psychopharmacology.
Safety at 1 year
The drug is a combination of extended-release serdexmethylphenidate (SDX), KemPharm’s prodrug of dexmethylphenidate, coformulated with immediate-release d-MPH.
SDX is converted to d-MPH after it is absorbed in the gastrointestinal tract. The d-MPH is released gradually throughout the day, providing quick symptom control with the d-MPH and extended control with SDX.
Azstarys was approved by the Food and Drug Administration in 2021 on the basis of results from a laboratory classroom phase 3 trial, which showed significant improvement in ADHD symptoms, compared with placebo.
For this study, the second phase 3 trial of Azstarys, investigators analyzed data from 282 children aged 6-12 years in the United States, including 70 who participated in an earlier 1-month efficacy trial.
After screening and a 3-week dose-optimization phase for new participants, patients received once-daily treatment with doses of 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, or 52.3 mg/10.4 mg of SDX/d-MPH.
After 1 year of treatment, 60.1% of participants reported at least one TEAE, the majority of which were moderate. Twelve patients reported severe TEAEs. Six children (2.5%) discontinued the study because of a TEAE during the treatment phase.
The investigators also measured growth and changes in sleep with the Children’s Sleep Habits Questionnaire during the 12-month study. Sleep improved on most measures and the impact on growth was mild.
There were no life-threatening TEAEs and no deaths reported during the study.
The most common TEAEs during the treatment phase were decreased appetite, upper respiratory tract infection, nasopharyngitis, decreased weight, irritability, and increased weight.
Efficacy at 1 year
ADHD symptoms improved considerably after 1 month of treatment, with responses continuing at 1 year.
At baseline, participants’ mean ADHD Rating Scale–5 score was 41.5. After 1 month of treatment, scores averaged 16.1, a decline of –25.3 (P < .001).
The mean score stabilized in the 12-15 range for the remainder of the study. After 1 year of treatment, ADHD symptoms had decreased approximately 70% from baseline.
Investigators found similar results in clinical severity. After 1 month of treatment, the average Clinical Global Impressions–Severity (CGI-S) scale score was 2.5, a decline of –2.2 (P < .0001).
CGI-S scale scores remained in the 2.2-2.4 range for the remainder of the study.
These results, combined with the results of the original classroom trial, suggest Azstarys may offer advantages over other ADHD drugs, Dr. Childress said.
“In the laboratory classroom trial, subjects taking Azstarys completed significantly more math problems than subjects taking placebo beginning at 30 minutes and up to 13 hours after dosing,” Dr. Childress said. “No other methylphenidate extended-release product currently marketed in the United States has a 13-hour duration of effect.”
‘Reassuring data’
Commenting on the findings, Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, said that the study suggests the drug may be a valuable addition to ADHD treatment options for pediatric patients.
“The study provides reassuring data on the safety of stimulants in patients without significant history of cardiac events or blood pressure changes, which are usual concerns among patients and clinicians despite the evidence supporting safety, said Dr. Pawar, who was not part of the study.
“Additionally, the 1-year data on efficacy and safety of a new stimulant medication is valuable for clinicians looking for sustained relief for their patients, despite the limitations of an open-label trial,” she added.
Overall, the safety data reported in the study are fairly consistent with the safety profile of other methylphenidates used for treating ADHD, Dr. Pawar said.
However, she noted, the study does have some limitations, including its open-label design and lack of blinding. The research also excluded children with autism, disruptive mood dysregulation disorders, and other common comorbidities of ADHD, which may limit the generalizability of the results.
“These comorbidities often require stimulants as a part of treatment, and yet have a higher risk of side effects,” Dr. Pawar said. “Future studies with a broader population may be needed to better understand treatment effectiveness and potential risks.”
The study was funded by KemPharm. Dr. Childress serves as consultant for Aardvark, Arbor, Attentive, Cingulate, Ironshore, Neos Therapeutics, Neurocentria, Otsuka, Purdue, Rhodes, Sunovion, Tris Pharma, KemPharm, Supernus, Jazz, Corium, Tulex, and Lumos.
A version of this article first appeared on Medscape.com.
new research shows.
Results from a phase 3, multicenter, dose-optimization, open-label safety study of Azstarys (KemPharm) found that most treatment-emergent adverse events (TEAEs) were mild to moderate.
“This data show that Azstarys remains safe and effective for the treatment of ADHD when given for up to a year,” lead investigator Ann Childress, MD, president of the Center for Psychiatry and Behavioral Medicine, Las Vegas, said in an interview.
The study was published online in the Journal of Child and Adolescent Psychopharmacology.
Safety at 1 year
The drug is a combination of extended-release serdexmethylphenidate (SDX), KemPharm’s prodrug of dexmethylphenidate, coformulated with immediate-release d-MPH.
SDX is converted to d-MPH after it is absorbed in the gastrointestinal tract. The d-MPH is released gradually throughout the day, providing quick symptom control with the d-MPH and extended control with SDX.
Azstarys was approved by the Food and Drug Administration in 2021 on the basis of results from a laboratory classroom phase 3 trial, which showed significant improvement in ADHD symptoms, compared with placebo.
For this study, the second phase 3 trial of Azstarys, investigators analyzed data from 282 children aged 6-12 years in the United States, including 70 who participated in an earlier 1-month efficacy trial.
After screening and a 3-week dose-optimization phase for new participants, patients received once-daily treatment with doses of 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, or 52.3 mg/10.4 mg of SDX/d-MPH.
After 1 year of treatment, 60.1% of participants reported at least one TEAE, the majority of which were moderate. Twelve patients reported severe TEAEs. Six children (2.5%) discontinued the study because of a TEAE during the treatment phase.
The investigators also measured growth and changes in sleep with the Children’s Sleep Habits Questionnaire during the 12-month study. Sleep improved on most measures and the impact on growth was mild.
There were no life-threatening TEAEs and no deaths reported during the study.
The most common TEAEs during the treatment phase were decreased appetite, upper respiratory tract infection, nasopharyngitis, decreased weight, irritability, and increased weight.
Efficacy at 1 year
ADHD symptoms improved considerably after 1 month of treatment, with responses continuing at 1 year.
At baseline, participants’ mean ADHD Rating Scale–5 score was 41.5. After 1 month of treatment, scores averaged 16.1, a decline of –25.3 (P < .001).
The mean score stabilized in the 12-15 range for the remainder of the study. After 1 year of treatment, ADHD symptoms had decreased approximately 70% from baseline.
Investigators found similar results in clinical severity. After 1 month of treatment, the average Clinical Global Impressions–Severity (CGI-S) scale score was 2.5, a decline of –2.2 (P < .0001).
CGI-S scale scores remained in the 2.2-2.4 range for the remainder of the study.
These results, combined with the results of the original classroom trial, suggest Azstarys may offer advantages over other ADHD drugs, Dr. Childress said.
“In the laboratory classroom trial, subjects taking Azstarys completed significantly more math problems than subjects taking placebo beginning at 30 minutes and up to 13 hours after dosing,” Dr. Childress said. “No other methylphenidate extended-release product currently marketed in the United States has a 13-hour duration of effect.”
‘Reassuring data’
Commenting on the findings, Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, said that the study suggests the drug may be a valuable addition to ADHD treatment options for pediatric patients.
“The study provides reassuring data on the safety of stimulants in patients without significant history of cardiac events or blood pressure changes, which are usual concerns among patients and clinicians despite the evidence supporting safety, said Dr. Pawar, who was not part of the study.
“Additionally, the 1-year data on efficacy and safety of a new stimulant medication is valuable for clinicians looking for sustained relief for their patients, despite the limitations of an open-label trial,” she added.
Overall, the safety data reported in the study are fairly consistent with the safety profile of other methylphenidates used for treating ADHD, Dr. Pawar said.
However, she noted, the study does have some limitations, including its open-label design and lack of blinding. The research also excluded children with autism, disruptive mood dysregulation disorders, and other common comorbidities of ADHD, which may limit the generalizability of the results.
“These comorbidities often require stimulants as a part of treatment, and yet have a higher risk of side effects,” Dr. Pawar said. “Future studies with a broader population may be needed to better understand treatment effectiveness and potential risks.”
The study was funded by KemPharm. Dr. Childress serves as consultant for Aardvark, Arbor, Attentive, Cingulate, Ironshore, Neos Therapeutics, Neurocentria, Otsuka, Purdue, Rhodes, Sunovion, Tris Pharma, KemPharm, Supernus, Jazz, Corium, Tulex, and Lumos.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
Depressive symptoms tied to higher stroke risk, worse outcomes
new research suggests.
Data from the international INTERSTROKE study also showed that those with depressive symptoms before a stroke had worse outcomes, including a significantly higher mortality rate in the first month after a stroke.
These findings build on prior research on the link between depression and stroke, including one study that showed an increased risk for incident stroke among those with a high number of depressive symptoms and another that found that worsening depression can precede stroke in older adults.
“Depression is an important risk factor for acute stroke and is potentially a modifiable contributor to the global burden of stroke,” lead investigator Robert Murphy, MB, a consultant in stroke and geriatric medicine and a researcher with the clinical research facility at the University of Galway, Ireland, told this news organization. “Even mild depressive symptoms were found in this study to be associated with increased risk of stroke and this adds to the literature that across the full range of depressive symptoms there is an association with increased risk of stroke.”
The findings were published online March 8 in Neurology.
Significant stroke risk
For the analysis, investigators collected data on 26,877 cases and controls across 32 countries who participated in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. Participants were recruited between 2007 and 2015 and completed a series of questionnaires about stroke risk factors, including measures of depressive symptoms experienced in the past 12 months.
After adjustment for occupation, education, wealth index, diet, physical activity, alcohol consumption, and smoking history, having prestroke depressive symptoms was associated with greater odds for acute stroke (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.34-1.58), including both intracerebral hemorrhage (aOR, 1.56; 95% CI, 1.28-1.91) and ischemic stroke (aOR, 1.44; 95% CI, 1.31-1.58).
Stroke risk increased with increasing severity of depression, but even those with mild depression had a 35% increased risk (aOR, 1.35; 95% CI, 1.19-1.53).
The increased risk held even after the researchers adjusted further for diabetes, hypertension, atrial fibrillation, and body mass index, and work, home, and financial stress.
The association was consistent across geographical regions and age groups, but was stronger in men and in those without hypertension.
“This study looks at different constructs of depression and identifies that across the spectrum of mild, moderate, and severe depressive symptoms that there is an association present with acute stroke and that a biological gradient emerges with increasing burden of depressive symptoms associated with increasing risk,” Dr. Murphy said.
An antidepressant mediating effect?
While prestroke depressive symptoms were not associated with a greater odds of worse stroke severity, they were associated with worse outcomes (P < .001) and higher mortality (10% vs. 8.1%; P = .003) 1 month after a stroke.
In a subgroup analysis, researchers found no association between depressive symptoms and stroke risk in patients who were taking antidepressants.
While no assumptions of causality can be drawn from these findings, “this subgroup analysis does suggest that an increased risk of stroke in those with depression may be attenuated if a patient is on appropriate treatment,” Dr. Murphy said. “This is an area that warrants further exploration.”
The mechanisms that link depression to stroke are unclear, but these findings offer strong evidence that this link exists, Dr. Murphy said.
“We adjusted for potential confounders in sequential models and after adjusting for traditional cardiovascular risk factors there was a consistent association between depressive symptoms and stroke identifying that there is likely an independent association between depression and stroke,” Dr. Murphy said.
Questions remain
Commenting on the study, Daniel T. Lackland DrPH, professor, division of translational neurosciences and population studies, department of neurology, Medical University of South Carolina, Charleston, said it adds to a growing body of work on the association of stroke and depression.
“In this case, depression may be a risk factor for having a stroke,” said Dr. Lackland, who was not part of the study. In addition, the study suggests that “treating depression can have additional benefits beyond mental health, in this case, reduced stroke risks.”
However, it’s important, as with any observational study, that there may be confounding factors that may offer an alternative explanation for the findings.
“Further, it is often difficult to accurately assess depression in all individuals, and specifically in individuals who have had a stroke,” Dr. Lackland said. “While this particular study adds depression as a risk factor and suggests treatment of depression in reducing risks, it is important to emphasize that the traditional stroke risk factors including hypertension should [be] continually recognized and treat[ed] with high rigor.”
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canadian Stroke Network, the Swedish Research Council, the Swedish Heart Lung Foundation, AFA Insurance, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), Merck Sharp & Dohme, the Swedish Heart Lung Foundation, Chest Heart & Stroke Scotland, and the Stroke Association (United Kingdom). Dr. Murphy and Dr. Lackland have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Data from the international INTERSTROKE study also showed that those with depressive symptoms before a stroke had worse outcomes, including a significantly higher mortality rate in the first month after a stroke.
These findings build on prior research on the link between depression and stroke, including one study that showed an increased risk for incident stroke among those with a high number of depressive symptoms and another that found that worsening depression can precede stroke in older adults.
“Depression is an important risk factor for acute stroke and is potentially a modifiable contributor to the global burden of stroke,” lead investigator Robert Murphy, MB, a consultant in stroke and geriatric medicine and a researcher with the clinical research facility at the University of Galway, Ireland, told this news organization. “Even mild depressive symptoms were found in this study to be associated with increased risk of stroke and this adds to the literature that across the full range of depressive symptoms there is an association with increased risk of stroke.”
The findings were published online March 8 in Neurology.
Significant stroke risk
For the analysis, investigators collected data on 26,877 cases and controls across 32 countries who participated in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. Participants were recruited between 2007 and 2015 and completed a series of questionnaires about stroke risk factors, including measures of depressive symptoms experienced in the past 12 months.
After adjustment for occupation, education, wealth index, diet, physical activity, alcohol consumption, and smoking history, having prestroke depressive symptoms was associated with greater odds for acute stroke (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.34-1.58), including both intracerebral hemorrhage (aOR, 1.56; 95% CI, 1.28-1.91) and ischemic stroke (aOR, 1.44; 95% CI, 1.31-1.58).
Stroke risk increased with increasing severity of depression, but even those with mild depression had a 35% increased risk (aOR, 1.35; 95% CI, 1.19-1.53).
The increased risk held even after the researchers adjusted further for diabetes, hypertension, atrial fibrillation, and body mass index, and work, home, and financial stress.
The association was consistent across geographical regions and age groups, but was stronger in men and in those without hypertension.
“This study looks at different constructs of depression and identifies that across the spectrum of mild, moderate, and severe depressive symptoms that there is an association present with acute stroke and that a biological gradient emerges with increasing burden of depressive symptoms associated with increasing risk,” Dr. Murphy said.
An antidepressant mediating effect?
While prestroke depressive symptoms were not associated with a greater odds of worse stroke severity, they were associated with worse outcomes (P < .001) and higher mortality (10% vs. 8.1%; P = .003) 1 month after a stroke.
In a subgroup analysis, researchers found no association between depressive symptoms and stroke risk in patients who were taking antidepressants.
While no assumptions of causality can be drawn from these findings, “this subgroup analysis does suggest that an increased risk of stroke in those with depression may be attenuated if a patient is on appropriate treatment,” Dr. Murphy said. “This is an area that warrants further exploration.”
The mechanisms that link depression to stroke are unclear, but these findings offer strong evidence that this link exists, Dr. Murphy said.
“We adjusted for potential confounders in sequential models and after adjusting for traditional cardiovascular risk factors there was a consistent association between depressive symptoms and stroke identifying that there is likely an independent association between depression and stroke,” Dr. Murphy said.
Questions remain
Commenting on the study, Daniel T. Lackland DrPH, professor, division of translational neurosciences and population studies, department of neurology, Medical University of South Carolina, Charleston, said it adds to a growing body of work on the association of stroke and depression.
“In this case, depression may be a risk factor for having a stroke,” said Dr. Lackland, who was not part of the study. In addition, the study suggests that “treating depression can have additional benefits beyond mental health, in this case, reduced stroke risks.”
However, it’s important, as with any observational study, that there may be confounding factors that may offer an alternative explanation for the findings.
“Further, it is often difficult to accurately assess depression in all individuals, and specifically in individuals who have had a stroke,” Dr. Lackland said. “While this particular study adds depression as a risk factor and suggests treatment of depression in reducing risks, it is important to emphasize that the traditional stroke risk factors including hypertension should [be] continually recognized and treat[ed] with high rigor.”
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canadian Stroke Network, the Swedish Research Council, the Swedish Heart Lung Foundation, AFA Insurance, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), Merck Sharp & Dohme, the Swedish Heart Lung Foundation, Chest Heart & Stroke Scotland, and the Stroke Association (United Kingdom). Dr. Murphy and Dr. Lackland have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Data from the international INTERSTROKE study also showed that those with depressive symptoms before a stroke had worse outcomes, including a significantly higher mortality rate in the first month after a stroke.
These findings build on prior research on the link between depression and stroke, including one study that showed an increased risk for incident stroke among those with a high number of depressive symptoms and another that found that worsening depression can precede stroke in older adults.
“Depression is an important risk factor for acute stroke and is potentially a modifiable contributor to the global burden of stroke,” lead investigator Robert Murphy, MB, a consultant in stroke and geriatric medicine and a researcher with the clinical research facility at the University of Galway, Ireland, told this news organization. “Even mild depressive symptoms were found in this study to be associated with increased risk of stroke and this adds to the literature that across the full range of depressive symptoms there is an association with increased risk of stroke.”
The findings were published online March 8 in Neurology.
Significant stroke risk
For the analysis, investigators collected data on 26,877 cases and controls across 32 countries who participated in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. Participants were recruited between 2007 and 2015 and completed a series of questionnaires about stroke risk factors, including measures of depressive symptoms experienced in the past 12 months.
After adjustment for occupation, education, wealth index, diet, physical activity, alcohol consumption, and smoking history, having prestroke depressive symptoms was associated with greater odds for acute stroke (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.34-1.58), including both intracerebral hemorrhage (aOR, 1.56; 95% CI, 1.28-1.91) and ischemic stroke (aOR, 1.44; 95% CI, 1.31-1.58).
Stroke risk increased with increasing severity of depression, but even those with mild depression had a 35% increased risk (aOR, 1.35; 95% CI, 1.19-1.53).
The increased risk held even after the researchers adjusted further for diabetes, hypertension, atrial fibrillation, and body mass index, and work, home, and financial stress.
The association was consistent across geographical regions and age groups, but was stronger in men and in those without hypertension.
“This study looks at different constructs of depression and identifies that across the spectrum of mild, moderate, and severe depressive symptoms that there is an association present with acute stroke and that a biological gradient emerges with increasing burden of depressive symptoms associated with increasing risk,” Dr. Murphy said.
An antidepressant mediating effect?
While prestroke depressive symptoms were not associated with a greater odds of worse stroke severity, they were associated with worse outcomes (P < .001) and higher mortality (10% vs. 8.1%; P = .003) 1 month after a stroke.
In a subgroup analysis, researchers found no association between depressive symptoms and stroke risk in patients who were taking antidepressants.
While no assumptions of causality can be drawn from these findings, “this subgroup analysis does suggest that an increased risk of stroke in those with depression may be attenuated if a patient is on appropriate treatment,” Dr. Murphy said. “This is an area that warrants further exploration.”
The mechanisms that link depression to stroke are unclear, but these findings offer strong evidence that this link exists, Dr. Murphy said.
“We adjusted for potential confounders in sequential models and after adjusting for traditional cardiovascular risk factors there was a consistent association between depressive symptoms and stroke identifying that there is likely an independent association between depression and stroke,” Dr. Murphy said.
Questions remain
Commenting on the study, Daniel T. Lackland DrPH, professor, division of translational neurosciences and population studies, department of neurology, Medical University of South Carolina, Charleston, said it adds to a growing body of work on the association of stroke and depression.
“In this case, depression may be a risk factor for having a stroke,” said Dr. Lackland, who was not part of the study. In addition, the study suggests that “treating depression can have additional benefits beyond mental health, in this case, reduced stroke risks.”
However, it’s important, as with any observational study, that there may be confounding factors that may offer an alternative explanation for the findings.
“Further, it is often difficult to accurately assess depression in all individuals, and specifically in individuals who have had a stroke,” Dr. Lackland said. “While this particular study adds depression as a risk factor and suggests treatment of depression in reducing risks, it is important to emphasize that the traditional stroke risk factors including hypertension should [be] continually recognized and treat[ed] with high rigor.”
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canadian Stroke Network, the Swedish Research Council, the Swedish Heart Lung Foundation, AFA Insurance, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), Merck Sharp & Dohme, the Swedish Heart Lung Foundation, Chest Heart & Stroke Scotland, and the Stroke Association (United Kingdom). Dr. Murphy and Dr. Lackland have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY