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Small fiber neuropathy is rising in the U.S., but why is a mystery
The exact reason for the increase in isolated SFN “remains unclear,” said Christopher J. Klein, MD, of the Mayo Clinic in Rochester, Minn. However, “we noted during the study period the population has had increased BMI, which appears to be a risk factor for this disorder, with many (50%) developing either glucose impairment or frank diabetes during the study period even if not present at first small fiber neuropathy presentation, also with associated higher triglyceride levels,” he explained.
The study was published online October 27 in Neurology.
Significant upward trend
Investigators reviewed the records of all 94 adults diagnosed with pure SFN (no large fiber involvement) between 1998 and 2017 in Olmsted and adjacent counties in Minnesota – and compared them with 282 adults of similar age and gender who did not have neuropathy.
The incidence of SFN over the entire study period was 1.3 per 100,000 per year and the prevalence was 13.3 per 100,000.
There was a “significant upward trend” in SFN incidence over the study period that could not be attributed to the availability of intraepidermal nerve fiber density testing, the authors reported.
The median age of onset of SFN was 54 years and two-thirds were women (67%).
Diabetes, obesity, and hypertriglyceridemia were significantly more common in patients with SFN compared with matched controls. These metabolic risk factors are also associated with peripheral neuropathy regardless of fiber type.
Autonomic symptoms were common and generally mild, affecting 85% of patients with SFN, and included male erectile dysfunction, constipation, light-headedness and palpitations, urinary symptoms, diarrhea, dry eyes and mouth, sweat abnormalities, and gastroparesis.
Insomnia and use of opioid pain medication were more common in those with SFN than matched controls.
More than one-third (36%) of patients with SFN developed large fiber neuropathy an average of 5.3 years after developing SFN.
During an average follow-up of 6.1 years, adults with SFN were significantly more likely to suffer myocardial infarction (46% vs. 27%; odds ratio, 2.0; 95% CI, 1.8-4.9), congestive heart failure (27% vs. 12%; OR, 2.6; 95% CI, 1.4-4.8), peripheral vascular disease (22% vs. 6%; OR, 4.0; 95% CI, 1.9-8.1), stroke (24% vs. 10%; OR, 2.8; 95% CI, 1.5-5.3), diabetes (51% vs. 22%; OR, 4.6; 95% CI, 2.8-7.6) and rheumatologic disease (30% vs. 7%; OR, 5.3; 95% CI, 2.8-10.4).
For 70% of patients, no cause for SFN could be determined. Diabetes (15%) was the most common cause identified. Other less common causes included Sjögren syndrome, lupus, amyloidosis, and Fabry disease.
“It is important to quantitatively diagnose patients with SFN as many non-neurological musculoskeletal causes can mimic the disorder,” said Dr. Klein.
“If rates of progression are rapid, sinister causes such as out-of-control diabetes, hereditary [transthyretin] TTR amyloidosis, and Fabry disease can be responsible. For other patients, rates of progression are slow and generally do not lead to significant neurologic impairments,” he added.
“However,” he said, “internal medicine follow-up is important for all as this disorder associates with development with higher risk of cardiovascular disease, including commonly heart attacks.”
Of note, although mean age at death was not significantly different in patients with SFN than controls (70 vs. 73 years), there was a significantly higher number of deaths in patients with SFN (n = 18; 19%) than in matched controls (n = 35; 12%) from the time of symptom onset, the researchers reported.
Important research
This “important” study sheds light on the comorbidities and longitudinal consequences of SFN, wrote Brian Callaghan, MD, with the University of Michigan, Ann Arbor, and J. Robinson Singleton, MD, with the University of Utah, Salt Lake City, in an accompanying editorial in Neurology.
The study demonstrates clearly that SFN has “metabolic risk factors similar to those seen for sensory predominant peripheral neuropathies affecting a broader range of fiber types. As a result, therapies that address metabolic risk factors are likely to help prevent or treat both conditions,” they wrote.
Dr. Callaghan and Dr. Singleton added that a key strength of the study is the detailed follow-up that examines SFN progression over time. “The authors found that patients with SFN do not report high disability and that progression tends to be slow. Therefore, patients with SFN can be counseled that progression and disability are likely to be modest in most cases. However, when patients do progress quickly, uncommon etiologies should be sought,” the editorialists wrote.
The study was supported by the Mayo Clinic Foundation, Mayo Clinic Center for Individualized Medicine, and Mayo Clinic Center of MS and Autoimmune Neurology. Dr. Klein has received teaching honorarium from Ackea pharmaceuticals for lectures on hereditary transthyretin amyloidosis and Fabry disease, consulted for Pfizer regarding tafamidis (all compensation for consulting activities is paid directly to Mayo Clinic), and participated in the clinical trials for inotersen and patisiran but received no personal compensation for his participation. Dr. Callaghan consults for DynaMed, performs medical legal consultations, including consultations for the Vaccine Injury Compensation Program, and receives research support from the American Academy of Neurology. Dr. Singleton has consulted for Regenacy.
A version of this article first appeared on Medscape.com.
The exact reason for the increase in isolated SFN “remains unclear,” said Christopher J. Klein, MD, of the Mayo Clinic in Rochester, Minn. However, “we noted during the study period the population has had increased BMI, which appears to be a risk factor for this disorder, with many (50%) developing either glucose impairment or frank diabetes during the study period even if not present at first small fiber neuropathy presentation, also with associated higher triglyceride levels,” he explained.
The study was published online October 27 in Neurology.
Significant upward trend
Investigators reviewed the records of all 94 adults diagnosed with pure SFN (no large fiber involvement) between 1998 and 2017 in Olmsted and adjacent counties in Minnesota – and compared them with 282 adults of similar age and gender who did not have neuropathy.
The incidence of SFN over the entire study period was 1.3 per 100,000 per year and the prevalence was 13.3 per 100,000.
There was a “significant upward trend” in SFN incidence over the study period that could not be attributed to the availability of intraepidermal nerve fiber density testing, the authors reported.
The median age of onset of SFN was 54 years and two-thirds were women (67%).
Diabetes, obesity, and hypertriglyceridemia were significantly more common in patients with SFN compared with matched controls. These metabolic risk factors are also associated with peripheral neuropathy regardless of fiber type.
Autonomic symptoms were common and generally mild, affecting 85% of patients with SFN, and included male erectile dysfunction, constipation, light-headedness and palpitations, urinary symptoms, diarrhea, dry eyes and mouth, sweat abnormalities, and gastroparesis.
Insomnia and use of opioid pain medication were more common in those with SFN than matched controls.
More than one-third (36%) of patients with SFN developed large fiber neuropathy an average of 5.3 years after developing SFN.
During an average follow-up of 6.1 years, adults with SFN were significantly more likely to suffer myocardial infarction (46% vs. 27%; odds ratio, 2.0; 95% CI, 1.8-4.9), congestive heart failure (27% vs. 12%; OR, 2.6; 95% CI, 1.4-4.8), peripheral vascular disease (22% vs. 6%; OR, 4.0; 95% CI, 1.9-8.1), stroke (24% vs. 10%; OR, 2.8; 95% CI, 1.5-5.3), diabetes (51% vs. 22%; OR, 4.6; 95% CI, 2.8-7.6) and rheumatologic disease (30% vs. 7%; OR, 5.3; 95% CI, 2.8-10.4).
For 70% of patients, no cause for SFN could be determined. Diabetes (15%) was the most common cause identified. Other less common causes included Sjögren syndrome, lupus, amyloidosis, and Fabry disease.
“It is important to quantitatively diagnose patients with SFN as many non-neurological musculoskeletal causes can mimic the disorder,” said Dr. Klein.
“If rates of progression are rapid, sinister causes such as out-of-control diabetes, hereditary [transthyretin] TTR amyloidosis, and Fabry disease can be responsible. For other patients, rates of progression are slow and generally do not lead to significant neurologic impairments,” he added.
“However,” he said, “internal medicine follow-up is important for all as this disorder associates with development with higher risk of cardiovascular disease, including commonly heart attacks.”
Of note, although mean age at death was not significantly different in patients with SFN than controls (70 vs. 73 years), there was a significantly higher number of deaths in patients with SFN (n = 18; 19%) than in matched controls (n = 35; 12%) from the time of symptom onset, the researchers reported.
Important research
This “important” study sheds light on the comorbidities and longitudinal consequences of SFN, wrote Brian Callaghan, MD, with the University of Michigan, Ann Arbor, and J. Robinson Singleton, MD, with the University of Utah, Salt Lake City, in an accompanying editorial in Neurology.
The study demonstrates clearly that SFN has “metabolic risk factors similar to those seen for sensory predominant peripheral neuropathies affecting a broader range of fiber types. As a result, therapies that address metabolic risk factors are likely to help prevent or treat both conditions,” they wrote.
Dr. Callaghan and Dr. Singleton added that a key strength of the study is the detailed follow-up that examines SFN progression over time. “The authors found that patients with SFN do not report high disability and that progression tends to be slow. Therefore, patients with SFN can be counseled that progression and disability are likely to be modest in most cases. However, when patients do progress quickly, uncommon etiologies should be sought,” the editorialists wrote.
The study was supported by the Mayo Clinic Foundation, Mayo Clinic Center for Individualized Medicine, and Mayo Clinic Center of MS and Autoimmune Neurology. Dr. Klein has received teaching honorarium from Ackea pharmaceuticals for lectures on hereditary transthyretin amyloidosis and Fabry disease, consulted for Pfizer regarding tafamidis (all compensation for consulting activities is paid directly to Mayo Clinic), and participated in the clinical trials for inotersen and patisiran but received no personal compensation for his participation. Dr. Callaghan consults for DynaMed, performs medical legal consultations, including consultations for the Vaccine Injury Compensation Program, and receives research support from the American Academy of Neurology. Dr. Singleton has consulted for Regenacy.
A version of this article first appeared on Medscape.com.
The exact reason for the increase in isolated SFN “remains unclear,” said Christopher J. Klein, MD, of the Mayo Clinic in Rochester, Minn. However, “we noted during the study period the population has had increased BMI, which appears to be a risk factor for this disorder, with many (50%) developing either glucose impairment or frank diabetes during the study period even if not present at first small fiber neuropathy presentation, also with associated higher triglyceride levels,” he explained.
The study was published online October 27 in Neurology.
Significant upward trend
Investigators reviewed the records of all 94 adults diagnosed with pure SFN (no large fiber involvement) between 1998 and 2017 in Olmsted and adjacent counties in Minnesota – and compared them with 282 adults of similar age and gender who did not have neuropathy.
The incidence of SFN over the entire study period was 1.3 per 100,000 per year and the prevalence was 13.3 per 100,000.
There was a “significant upward trend” in SFN incidence over the study period that could not be attributed to the availability of intraepidermal nerve fiber density testing, the authors reported.
The median age of onset of SFN was 54 years and two-thirds were women (67%).
Diabetes, obesity, and hypertriglyceridemia were significantly more common in patients with SFN compared with matched controls. These metabolic risk factors are also associated with peripheral neuropathy regardless of fiber type.
Autonomic symptoms were common and generally mild, affecting 85% of patients with SFN, and included male erectile dysfunction, constipation, light-headedness and palpitations, urinary symptoms, diarrhea, dry eyes and mouth, sweat abnormalities, and gastroparesis.
Insomnia and use of opioid pain medication were more common in those with SFN than matched controls.
More than one-third (36%) of patients with SFN developed large fiber neuropathy an average of 5.3 years after developing SFN.
During an average follow-up of 6.1 years, adults with SFN were significantly more likely to suffer myocardial infarction (46% vs. 27%; odds ratio, 2.0; 95% CI, 1.8-4.9), congestive heart failure (27% vs. 12%; OR, 2.6; 95% CI, 1.4-4.8), peripheral vascular disease (22% vs. 6%; OR, 4.0; 95% CI, 1.9-8.1), stroke (24% vs. 10%; OR, 2.8; 95% CI, 1.5-5.3), diabetes (51% vs. 22%; OR, 4.6; 95% CI, 2.8-7.6) and rheumatologic disease (30% vs. 7%; OR, 5.3; 95% CI, 2.8-10.4).
For 70% of patients, no cause for SFN could be determined. Diabetes (15%) was the most common cause identified. Other less common causes included Sjögren syndrome, lupus, amyloidosis, and Fabry disease.
“It is important to quantitatively diagnose patients with SFN as many non-neurological musculoskeletal causes can mimic the disorder,” said Dr. Klein.
“If rates of progression are rapid, sinister causes such as out-of-control diabetes, hereditary [transthyretin] TTR amyloidosis, and Fabry disease can be responsible. For other patients, rates of progression are slow and generally do not lead to significant neurologic impairments,” he added.
“However,” he said, “internal medicine follow-up is important for all as this disorder associates with development with higher risk of cardiovascular disease, including commonly heart attacks.”
Of note, although mean age at death was not significantly different in patients with SFN than controls (70 vs. 73 years), there was a significantly higher number of deaths in patients with SFN (n = 18; 19%) than in matched controls (n = 35; 12%) from the time of symptom onset, the researchers reported.
Important research
This “important” study sheds light on the comorbidities and longitudinal consequences of SFN, wrote Brian Callaghan, MD, with the University of Michigan, Ann Arbor, and J. Robinson Singleton, MD, with the University of Utah, Salt Lake City, in an accompanying editorial in Neurology.
The study demonstrates clearly that SFN has “metabolic risk factors similar to those seen for sensory predominant peripheral neuropathies affecting a broader range of fiber types. As a result, therapies that address metabolic risk factors are likely to help prevent or treat both conditions,” they wrote.
Dr. Callaghan and Dr. Singleton added that a key strength of the study is the detailed follow-up that examines SFN progression over time. “The authors found that patients with SFN do not report high disability and that progression tends to be slow. Therefore, patients with SFN can be counseled that progression and disability are likely to be modest in most cases. However, when patients do progress quickly, uncommon etiologies should be sought,” the editorialists wrote.
The study was supported by the Mayo Clinic Foundation, Mayo Clinic Center for Individualized Medicine, and Mayo Clinic Center of MS and Autoimmune Neurology. Dr. Klein has received teaching honorarium from Ackea pharmaceuticals for lectures on hereditary transthyretin amyloidosis and Fabry disease, consulted for Pfizer regarding tafamidis (all compensation for consulting activities is paid directly to Mayo Clinic), and participated in the clinical trials for inotersen and patisiran but received no personal compensation for his participation. Dr. Callaghan consults for DynaMed, performs medical legal consultations, including consultations for the Vaccine Injury Compensation Program, and receives research support from the American Academy of Neurology. Dr. Singleton has consulted for Regenacy.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Influenza tied to long-term increased risk for Parkinson’s disease
Influenza infection is linked to a subsequent diagnosis of Parkinson’s disease (PD) more than 10 years later, resurfacing a long-held debate about whether infection increases the risk for movement disorders over the long term.
In a large case-control study, investigators found and by more than 70% for PD occurring more than 10 years after the flu.
“This study is not definitive by any means, but it certainly suggests there are potential long-term consequences from influenza,” study investigator Noelle M. Cocoros, DSc, research scientist at Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, said in an interview.
The study was published online Oct. 25 in JAMA Neurology.
Ongoing debate
The debate about whether influenza is associated with PD has been going on as far back as the 1918 influenza pandemic, when experts documented parkinsonism in affected individuals.
Using data from the Danish patient registry, researchers identified 10,271 subjects diagnosed with PD during a 17-year period (2000-2016). Of these, 38.7% were female, and the mean age was 71.4 years.
They matched these subjects for age and sex to 51,355 controls without PD. Compared with controls, slightly fewer individuals with PD had chronic obstructive pulmonary disease (COPD) or emphysema, but there was a similar distribution of cardiovascular disease and various other conditions.
Researchers collected data on influenza diagnoses from inpatient and outpatient hospital clinics from 1977 to 2016. They plotted these by month and year on a graph, calculated the median number of diagnoses per month, and identified peaks as those with more than threefold the median.
They categorized cases in groups related to the time between the infection and PD: More than 10 years, 10-15 years, and more than 15 years.
The time lapse accounts for a rather long “run-up” to PD, said Dr. Cocoros. There’s a sometimes decades-long preclinical phase before patients develop typical motor signs and a prodromal phase where they may present with nonmotor symptoms such as sleep disorders and constipation.
“We expected there would be at least 10 years between any infection and PD if there was an association present,” said Dr. Cocoros.
Investigators found an association between influenza exposure and PD diagnosis “that held up over time,” she said.
For more than 10 years before PD, the likelihood of a diagnosis for the infected compared with the unexposed was increased 73% (odds ratio [OR] 1.73; 95% confidence interval, 1.11-2.71; P = .02) after adjustment for cardiovascular disease, diabetes, chronic obstructive pulmonary disease, emphysema, lung cancer, Crohn’s disease, and ulcerative colitis.
The odds increased with more time from infection. For more than 15 years, the adjusted OR was 1.91 (95% CI, 1.14 - 3.19; P =.01).
However, for the 10- to 15-year time frame, the point estimate was reduced and the CI nonsignificant (OR, 1.33; 95% CI, 0.54-3.27; P = .53). This “is a little hard to interpret,” but could be a result of the small numbers, exposure misclassification, or because “the longer time interval is what’s meaningful,” said Dr. Cocoros.
Potential COVID-19–related PD surge?
In a sensitivity analysis, researchers looked at peak infection activity. “We wanted to increase the likelihood of these diagnoses representing actual infection,” Dr. Cocoros noted.
Here, the OR was still elevated at more than 10 years, but the CI was quite wide and included 1 (OR, 1.52; 95% CI, 0.80-2.89; P = .21). “So the association holds up, but the estimates are quite unstable,” said Dr. Cocoros.
Researchers examined associations with numerous other infection types, but did not see the same trend over time. Some infections – for example, gastrointestinal infections and septicemia – were associated with PD within 5 years, but most associations appeared to be null after more than 10 years.
“There seemed to be associations earlier between the infection and PD, which we interpret to suggest there’s actually not a meaningful association,” said Dr. Cocoros.
An exception might be urinary tract infections (UTIs), where after 10 years, the adjusted OR was 1.19 (95% CI, 1.01-1.40). Research suggests patients with PD often have UTIs and neurogenic bladder.
“It’s possible that UTIs could be an early symptom of PD rather than a causative factor,” said Dr. Cocoros.
It’s unclear how influenza might lead to PD but it could be that the virus gets into the central nervous system, resulting in neuroinflammation. Cytokines generated in response to the influenza infection might damage the brain.
“The infection could be a ‘primer’ or an initial ‘hit’ to the system, maybe setting people up for PD,” said Dr. Cocoros.
As for the current COVID-19 pandemic, some experts are concerned about a potential surge in PD cases in decades to come, and are calling for prospective monitoring of patients with this infection, said Dr. Cocoros.
However, she noted that infections don’t account for all PD cases and that genetic and environmental factors also influence risk.
Many individuals who contract influenza don’t seek medical care or get tested, so it’s possible the study counted those who had the infection as unexposed. Another potential study limitation was that small numbers for some infections, for example, Helicobacter pylori and hepatitis C, limited the ability to interpret results.
‘Exciting and important’ findings
Commenting on the research for this news organization, Aparna Wagle Shukla, MD, professor, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, said the results amid the current pandemic are “exciting and important” and “have reinvigorated interest” in the role of infection in PD.
However, the study had some limitations, an important one being lack of accounting for confounding factors, including environmental factors, she said. Exposure to pesticides, living in a rural area, drinking well water, and having had a head injury may increase PD risk, whereas high intake of caffeine, nicotine, alcohol, and nonsteroidal anti-inflammatory drugs might lower the risk.
The researchers did not take into account exposure to multiple microbes or “infection burden,” said Dr. Wagle Shukla, who was not involved in the current study. In addition, as the data are from a single country with exposure to specific influenza strains, application of the findings elsewhere may be limited.
Dr. Wagle Shukla noted that a case-control design “isn’t ideal” from an epidemiological perspective. “Future studies should involve large cohorts followed longitudinally.”
The study was supported by grants from the Lundbeck Foundation and the Augustinus Foundation. Dr. Cocoros has disclosed no relevant financial relationships. Several coauthors have disclosed relationships with industry. The full list can be found with the original article.
A version of this article first appeared on Medscape.com.
Influenza infection is linked to a subsequent diagnosis of Parkinson’s disease (PD) more than 10 years later, resurfacing a long-held debate about whether infection increases the risk for movement disorders over the long term.
In a large case-control study, investigators found and by more than 70% for PD occurring more than 10 years after the flu.
“This study is not definitive by any means, but it certainly suggests there are potential long-term consequences from influenza,” study investigator Noelle M. Cocoros, DSc, research scientist at Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, said in an interview.
The study was published online Oct. 25 in JAMA Neurology.
Ongoing debate
The debate about whether influenza is associated with PD has been going on as far back as the 1918 influenza pandemic, when experts documented parkinsonism in affected individuals.
Using data from the Danish patient registry, researchers identified 10,271 subjects diagnosed with PD during a 17-year period (2000-2016). Of these, 38.7% were female, and the mean age was 71.4 years.
They matched these subjects for age and sex to 51,355 controls without PD. Compared with controls, slightly fewer individuals with PD had chronic obstructive pulmonary disease (COPD) or emphysema, but there was a similar distribution of cardiovascular disease and various other conditions.
Researchers collected data on influenza diagnoses from inpatient and outpatient hospital clinics from 1977 to 2016. They plotted these by month and year on a graph, calculated the median number of diagnoses per month, and identified peaks as those with more than threefold the median.
They categorized cases in groups related to the time between the infection and PD: More than 10 years, 10-15 years, and more than 15 years.
The time lapse accounts for a rather long “run-up” to PD, said Dr. Cocoros. There’s a sometimes decades-long preclinical phase before patients develop typical motor signs and a prodromal phase where they may present with nonmotor symptoms such as sleep disorders and constipation.
“We expected there would be at least 10 years between any infection and PD if there was an association present,” said Dr. Cocoros.
Investigators found an association between influenza exposure and PD diagnosis “that held up over time,” she said.
For more than 10 years before PD, the likelihood of a diagnosis for the infected compared with the unexposed was increased 73% (odds ratio [OR] 1.73; 95% confidence interval, 1.11-2.71; P = .02) after adjustment for cardiovascular disease, diabetes, chronic obstructive pulmonary disease, emphysema, lung cancer, Crohn’s disease, and ulcerative colitis.
The odds increased with more time from infection. For more than 15 years, the adjusted OR was 1.91 (95% CI, 1.14 - 3.19; P =.01).
However, for the 10- to 15-year time frame, the point estimate was reduced and the CI nonsignificant (OR, 1.33; 95% CI, 0.54-3.27; P = .53). This “is a little hard to interpret,” but could be a result of the small numbers, exposure misclassification, or because “the longer time interval is what’s meaningful,” said Dr. Cocoros.
Potential COVID-19–related PD surge?
In a sensitivity analysis, researchers looked at peak infection activity. “We wanted to increase the likelihood of these diagnoses representing actual infection,” Dr. Cocoros noted.
Here, the OR was still elevated at more than 10 years, but the CI was quite wide and included 1 (OR, 1.52; 95% CI, 0.80-2.89; P = .21). “So the association holds up, but the estimates are quite unstable,” said Dr. Cocoros.
Researchers examined associations with numerous other infection types, but did not see the same trend over time. Some infections – for example, gastrointestinal infections and septicemia – were associated with PD within 5 years, but most associations appeared to be null after more than 10 years.
“There seemed to be associations earlier between the infection and PD, which we interpret to suggest there’s actually not a meaningful association,” said Dr. Cocoros.
An exception might be urinary tract infections (UTIs), where after 10 years, the adjusted OR was 1.19 (95% CI, 1.01-1.40). Research suggests patients with PD often have UTIs and neurogenic bladder.
“It’s possible that UTIs could be an early symptom of PD rather than a causative factor,” said Dr. Cocoros.
It’s unclear how influenza might lead to PD but it could be that the virus gets into the central nervous system, resulting in neuroinflammation. Cytokines generated in response to the influenza infection might damage the brain.
“The infection could be a ‘primer’ or an initial ‘hit’ to the system, maybe setting people up for PD,” said Dr. Cocoros.
As for the current COVID-19 pandemic, some experts are concerned about a potential surge in PD cases in decades to come, and are calling for prospective monitoring of patients with this infection, said Dr. Cocoros.
However, she noted that infections don’t account for all PD cases and that genetic and environmental factors also influence risk.
Many individuals who contract influenza don’t seek medical care or get tested, so it’s possible the study counted those who had the infection as unexposed. Another potential study limitation was that small numbers for some infections, for example, Helicobacter pylori and hepatitis C, limited the ability to interpret results.
‘Exciting and important’ findings
Commenting on the research for this news organization, Aparna Wagle Shukla, MD, professor, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, said the results amid the current pandemic are “exciting and important” and “have reinvigorated interest” in the role of infection in PD.
However, the study had some limitations, an important one being lack of accounting for confounding factors, including environmental factors, she said. Exposure to pesticides, living in a rural area, drinking well water, and having had a head injury may increase PD risk, whereas high intake of caffeine, nicotine, alcohol, and nonsteroidal anti-inflammatory drugs might lower the risk.
The researchers did not take into account exposure to multiple microbes or “infection burden,” said Dr. Wagle Shukla, who was not involved in the current study. In addition, as the data are from a single country with exposure to specific influenza strains, application of the findings elsewhere may be limited.
Dr. Wagle Shukla noted that a case-control design “isn’t ideal” from an epidemiological perspective. “Future studies should involve large cohorts followed longitudinally.”
The study was supported by grants from the Lundbeck Foundation and the Augustinus Foundation. Dr. Cocoros has disclosed no relevant financial relationships. Several coauthors have disclosed relationships with industry. The full list can be found with the original article.
A version of this article first appeared on Medscape.com.
Influenza infection is linked to a subsequent diagnosis of Parkinson’s disease (PD) more than 10 years later, resurfacing a long-held debate about whether infection increases the risk for movement disorders over the long term.
In a large case-control study, investigators found and by more than 70% for PD occurring more than 10 years after the flu.
“This study is not definitive by any means, but it certainly suggests there are potential long-term consequences from influenza,” study investigator Noelle M. Cocoros, DSc, research scientist at Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, said in an interview.
The study was published online Oct. 25 in JAMA Neurology.
Ongoing debate
The debate about whether influenza is associated with PD has been going on as far back as the 1918 influenza pandemic, when experts documented parkinsonism in affected individuals.
Using data from the Danish patient registry, researchers identified 10,271 subjects diagnosed with PD during a 17-year period (2000-2016). Of these, 38.7% were female, and the mean age was 71.4 years.
They matched these subjects for age and sex to 51,355 controls without PD. Compared with controls, slightly fewer individuals with PD had chronic obstructive pulmonary disease (COPD) or emphysema, but there was a similar distribution of cardiovascular disease and various other conditions.
Researchers collected data on influenza diagnoses from inpatient and outpatient hospital clinics from 1977 to 2016. They plotted these by month and year on a graph, calculated the median number of diagnoses per month, and identified peaks as those with more than threefold the median.
They categorized cases in groups related to the time between the infection and PD: More than 10 years, 10-15 years, and more than 15 years.
The time lapse accounts for a rather long “run-up” to PD, said Dr. Cocoros. There’s a sometimes decades-long preclinical phase before patients develop typical motor signs and a prodromal phase where they may present with nonmotor symptoms such as sleep disorders and constipation.
“We expected there would be at least 10 years between any infection and PD if there was an association present,” said Dr. Cocoros.
Investigators found an association between influenza exposure and PD diagnosis “that held up over time,” she said.
For more than 10 years before PD, the likelihood of a diagnosis for the infected compared with the unexposed was increased 73% (odds ratio [OR] 1.73; 95% confidence interval, 1.11-2.71; P = .02) after adjustment for cardiovascular disease, diabetes, chronic obstructive pulmonary disease, emphysema, lung cancer, Crohn’s disease, and ulcerative colitis.
The odds increased with more time from infection. For more than 15 years, the adjusted OR was 1.91 (95% CI, 1.14 - 3.19; P =.01).
However, for the 10- to 15-year time frame, the point estimate was reduced and the CI nonsignificant (OR, 1.33; 95% CI, 0.54-3.27; P = .53). This “is a little hard to interpret,” but could be a result of the small numbers, exposure misclassification, or because “the longer time interval is what’s meaningful,” said Dr. Cocoros.
Potential COVID-19–related PD surge?
In a sensitivity analysis, researchers looked at peak infection activity. “We wanted to increase the likelihood of these diagnoses representing actual infection,” Dr. Cocoros noted.
Here, the OR was still elevated at more than 10 years, but the CI was quite wide and included 1 (OR, 1.52; 95% CI, 0.80-2.89; P = .21). “So the association holds up, but the estimates are quite unstable,” said Dr. Cocoros.
Researchers examined associations with numerous other infection types, but did not see the same trend over time. Some infections – for example, gastrointestinal infections and septicemia – were associated with PD within 5 years, but most associations appeared to be null after more than 10 years.
“There seemed to be associations earlier between the infection and PD, which we interpret to suggest there’s actually not a meaningful association,” said Dr. Cocoros.
An exception might be urinary tract infections (UTIs), where after 10 years, the adjusted OR was 1.19 (95% CI, 1.01-1.40). Research suggests patients with PD often have UTIs and neurogenic bladder.
“It’s possible that UTIs could be an early symptom of PD rather than a causative factor,” said Dr. Cocoros.
It’s unclear how influenza might lead to PD but it could be that the virus gets into the central nervous system, resulting in neuroinflammation. Cytokines generated in response to the influenza infection might damage the brain.
“The infection could be a ‘primer’ or an initial ‘hit’ to the system, maybe setting people up for PD,” said Dr. Cocoros.
As for the current COVID-19 pandemic, some experts are concerned about a potential surge in PD cases in decades to come, and are calling for prospective monitoring of patients with this infection, said Dr. Cocoros.
However, she noted that infections don’t account for all PD cases and that genetic and environmental factors also influence risk.
Many individuals who contract influenza don’t seek medical care or get tested, so it’s possible the study counted those who had the infection as unexposed. Another potential study limitation was that small numbers for some infections, for example, Helicobacter pylori and hepatitis C, limited the ability to interpret results.
‘Exciting and important’ findings
Commenting on the research for this news organization, Aparna Wagle Shukla, MD, professor, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, said the results amid the current pandemic are “exciting and important” and “have reinvigorated interest” in the role of infection in PD.
However, the study had some limitations, an important one being lack of accounting for confounding factors, including environmental factors, she said. Exposure to pesticides, living in a rural area, drinking well water, and having had a head injury may increase PD risk, whereas high intake of caffeine, nicotine, alcohol, and nonsteroidal anti-inflammatory drugs might lower the risk.
The researchers did not take into account exposure to multiple microbes or “infection burden,” said Dr. Wagle Shukla, who was not involved in the current study. In addition, as the data are from a single country with exposure to specific influenza strains, application of the findings elsewhere may be limited.
Dr. Wagle Shukla noted that a case-control design “isn’t ideal” from an epidemiological perspective. “Future studies should involve large cohorts followed longitudinally.”
The study was supported by grants from the Lundbeck Foundation and the Augustinus Foundation. Dr. Cocoros has disclosed no relevant financial relationships. Several coauthors have disclosed relationships with industry. The full list can be found with the original article.
A version of this article first appeared on Medscape.com.
Sleep time ‘sweet spot’ to slow cognitive decline identified?
In a longitudinal study, investigators found older adults who slept less than 4.5 hours or more than 6.5 hours a night reported significant cognitive decline over time, but cognitive scores for those with sleep duration in between that range remained stable.
“This really suggests that there’s this middle range, a ‘sweet spot,’ where your sleep is really optimal,” lead author Brendan Lucey, MD, MSCI, associate professor of neurology and director of the Washington University Sleep Medicine Center, St. Louis, said in an interview.
The study, published online Oct. 20, 2021, in the journal Brain, is part of a growing body of research that seeks to determine if sleep can be used as a marker of Alzheimer’s disease progression.
A complex relationship
Studies suggest a strong relationship between sleep patterns and Alzheimer’s disease, which affects nearly 6 million Americans. The challenge, Dr. Lucey said, is unwinding the complex links between sleep, AD, and cognitive function.
An earlier study by Dr. Lucey and colleagues found that poor sleep quality is associated with early signs of AD, and a report published in September found that elderly people who slept less than 6 hours a night had a greater burden of amyloid-beta, a hallmark sign of AD.
For this new study, researchers monitored sleep-wake activity over 4-6 nights in 100 participants who underwent annual cognitive assessments and clinical studies, including APOE genotyping, as part of a longitudinal study at the Knight Alzheimer Disease Research Center at Washington University.
Participants also provided cerebrospinal fluid (CSF) total tau and amyloid-beta 42 and wore a small EEG device on their forehead while they slept.
The majority of participants had a clinical dementia rating (CDR) score of 0, indicating no cognitive impairment. Twelve individuals had a CDR greater than 0, with most reporting mild cognitive impairment.
As expected, CSF analysis showed greater evidence of AD pathology in those with a baseline CDR greater than 0.
Changes in cognitive function were measured using a Preclinical Alzheimer Cognitive Composite (PACC) score, a composite of results from a neuropsychological testing battery that included the Free and Cued Selective Reminding Test, the Logical Memory Delayed Recall Test from the Wechsler Memory Scale–Revised, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale–Revised, and the Mini-Mental State Examination.
Researchers found an upside-down U-shaped relationship between PACC scores and sleep duration, with dramatic cognitive decline in those who slept less than 4.5 hours or more than 6.5 hours a night (P < .001 for both).
The U-shaped relationship was also found with measures of sleep phases, including time spent in rapid eye movement and in non-REM sleep (P < .001 for both).
The findings persisted even after controlling for confounders that can affect sleep and cognition, such as age, CSF total tau/amyloid-beta 42 ratio, apo E four-allele carrier status, years of education, and sex.
Understanding how sleep changes at different stages of AD could help researchers determine if sleep can be used as a marker of disease progression, Dr. Lucey said. That could lead to interventions to slow that process.
“We’re not at the point yet where we can say that we need to monitor someone’s sleep time and then do an intervention to see if it would improve their risk for cognitive decline,” said Dr. Lucey, who plans to repeat this sleep study with the same cohort to track changes in sleep patterns and cognitive function over time. “But that’s a question I’m very excited to try to answer.”
A component of cognitive health
Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, noted that the study adds to a body of evidence linking sleep and cognition, especially how sleep quality can optimize brain function.
“We’ve seen previous research that’s shown poor sleep contributes to dementia risk, as well as research showing sleep duration may play a role in cognition,” she said.
“We also need studies that look at sleep as an intervention for cognitive health,” Dr. Snyder said. “Sleep is an important aspect of our overall health. Clinicians should have conversations with their patients about sleep as part of standard discussions about their health habits and wellness.”
The study was funded by the National Institutes of Health, the American Sleep Medicine Foundation, the Roger and Paula Riney Fund, and the Daniel J. Brennan, MD Fund. Dr. Lucey consults for Merck and Eli Lilly. Dr. Snyder has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a longitudinal study, investigators found older adults who slept less than 4.5 hours or more than 6.5 hours a night reported significant cognitive decline over time, but cognitive scores for those with sleep duration in between that range remained stable.
“This really suggests that there’s this middle range, a ‘sweet spot,’ where your sleep is really optimal,” lead author Brendan Lucey, MD, MSCI, associate professor of neurology and director of the Washington University Sleep Medicine Center, St. Louis, said in an interview.
The study, published online Oct. 20, 2021, in the journal Brain, is part of a growing body of research that seeks to determine if sleep can be used as a marker of Alzheimer’s disease progression.
A complex relationship
Studies suggest a strong relationship between sleep patterns and Alzheimer’s disease, which affects nearly 6 million Americans. The challenge, Dr. Lucey said, is unwinding the complex links between sleep, AD, and cognitive function.
An earlier study by Dr. Lucey and colleagues found that poor sleep quality is associated with early signs of AD, and a report published in September found that elderly people who slept less than 6 hours a night had a greater burden of amyloid-beta, a hallmark sign of AD.
For this new study, researchers monitored sleep-wake activity over 4-6 nights in 100 participants who underwent annual cognitive assessments and clinical studies, including APOE genotyping, as part of a longitudinal study at the Knight Alzheimer Disease Research Center at Washington University.
Participants also provided cerebrospinal fluid (CSF) total tau and amyloid-beta 42 and wore a small EEG device on their forehead while they slept.
The majority of participants had a clinical dementia rating (CDR) score of 0, indicating no cognitive impairment. Twelve individuals had a CDR greater than 0, with most reporting mild cognitive impairment.
As expected, CSF analysis showed greater evidence of AD pathology in those with a baseline CDR greater than 0.
Changes in cognitive function were measured using a Preclinical Alzheimer Cognitive Composite (PACC) score, a composite of results from a neuropsychological testing battery that included the Free and Cued Selective Reminding Test, the Logical Memory Delayed Recall Test from the Wechsler Memory Scale–Revised, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale–Revised, and the Mini-Mental State Examination.
Researchers found an upside-down U-shaped relationship between PACC scores and sleep duration, with dramatic cognitive decline in those who slept less than 4.5 hours or more than 6.5 hours a night (P < .001 for both).
The U-shaped relationship was also found with measures of sleep phases, including time spent in rapid eye movement and in non-REM sleep (P < .001 for both).
The findings persisted even after controlling for confounders that can affect sleep and cognition, such as age, CSF total tau/amyloid-beta 42 ratio, apo E four-allele carrier status, years of education, and sex.
Understanding how sleep changes at different stages of AD could help researchers determine if sleep can be used as a marker of disease progression, Dr. Lucey said. That could lead to interventions to slow that process.
“We’re not at the point yet where we can say that we need to monitor someone’s sleep time and then do an intervention to see if it would improve their risk for cognitive decline,” said Dr. Lucey, who plans to repeat this sleep study with the same cohort to track changes in sleep patterns and cognitive function over time. “But that’s a question I’m very excited to try to answer.”
A component of cognitive health
Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, noted that the study adds to a body of evidence linking sleep and cognition, especially how sleep quality can optimize brain function.
“We’ve seen previous research that’s shown poor sleep contributes to dementia risk, as well as research showing sleep duration may play a role in cognition,” she said.
“We also need studies that look at sleep as an intervention for cognitive health,” Dr. Snyder said. “Sleep is an important aspect of our overall health. Clinicians should have conversations with their patients about sleep as part of standard discussions about their health habits and wellness.”
The study was funded by the National Institutes of Health, the American Sleep Medicine Foundation, the Roger and Paula Riney Fund, and the Daniel J. Brennan, MD Fund. Dr. Lucey consults for Merck and Eli Lilly. Dr. Snyder has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a longitudinal study, investigators found older adults who slept less than 4.5 hours or more than 6.5 hours a night reported significant cognitive decline over time, but cognitive scores for those with sleep duration in between that range remained stable.
“This really suggests that there’s this middle range, a ‘sweet spot,’ where your sleep is really optimal,” lead author Brendan Lucey, MD, MSCI, associate professor of neurology and director of the Washington University Sleep Medicine Center, St. Louis, said in an interview.
The study, published online Oct. 20, 2021, in the journal Brain, is part of a growing body of research that seeks to determine if sleep can be used as a marker of Alzheimer’s disease progression.
A complex relationship
Studies suggest a strong relationship between sleep patterns and Alzheimer’s disease, which affects nearly 6 million Americans. The challenge, Dr. Lucey said, is unwinding the complex links between sleep, AD, and cognitive function.
An earlier study by Dr. Lucey and colleagues found that poor sleep quality is associated with early signs of AD, and a report published in September found that elderly people who slept less than 6 hours a night had a greater burden of amyloid-beta, a hallmark sign of AD.
For this new study, researchers monitored sleep-wake activity over 4-6 nights in 100 participants who underwent annual cognitive assessments and clinical studies, including APOE genotyping, as part of a longitudinal study at the Knight Alzheimer Disease Research Center at Washington University.
Participants also provided cerebrospinal fluid (CSF) total tau and amyloid-beta 42 and wore a small EEG device on their forehead while they slept.
The majority of participants had a clinical dementia rating (CDR) score of 0, indicating no cognitive impairment. Twelve individuals had a CDR greater than 0, with most reporting mild cognitive impairment.
As expected, CSF analysis showed greater evidence of AD pathology in those with a baseline CDR greater than 0.
Changes in cognitive function were measured using a Preclinical Alzheimer Cognitive Composite (PACC) score, a composite of results from a neuropsychological testing battery that included the Free and Cued Selective Reminding Test, the Logical Memory Delayed Recall Test from the Wechsler Memory Scale–Revised, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale–Revised, and the Mini-Mental State Examination.
Researchers found an upside-down U-shaped relationship between PACC scores and sleep duration, with dramatic cognitive decline in those who slept less than 4.5 hours or more than 6.5 hours a night (P < .001 for both).
The U-shaped relationship was also found with measures of sleep phases, including time spent in rapid eye movement and in non-REM sleep (P < .001 for both).
The findings persisted even after controlling for confounders that can affect sleep and cognition, such as age, CSF total tau/amyloid-beta 42 ratio, apo E four-allele carrier status, years of education, and sex.
Understanding how sleep changes at different stages of AD could help researchers determine if sleep can be used as a marker of disease progression, Dr. Lucey said. That could lead to interventions to slow that process.
“We’re not at the point yet where we can say that we need to monitor someone’s sleep time and then do an intervention to see if it would improve their risk for cognitive decline,” said Dr. Lucey, who plans to repeat this sleep study with the same cohort to track changes in sleep patterns and cognitive function over time. “But that’s a question I’m very excited to try to answer.”
A component of cognitive health
Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, noted that the study adds to a body of evidence linking sleep and cognition, especially how sleep quality can optimize brain function.
“We’ve seen previous research that’s shown poor sleep contributes to dementia risk, as well as research showing sleep duration may play a role in cognition,” she said.
“We also need studies that look at sleep as an intervention for cognitive health,” Dr. Snyder said. “Sleep is an important aspect of our overall health. Clinicians should have conversations with their patients about sleep as part of standard discussions about their health habits and wellness.”
The study was funded by the National Institutes of Health, the American Sleep Medicine Foundation, the Roger and Paula Riney Fund, and the Daniel J. Brennan, MD Fund. Dr. Lucey consults for Merck and Eli Lilly. Dr. Snyder has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sleep time ‘sweet spot’ to slow cognitive decline identified?
In a longitudinal study, investigators found older adults who slept less than 4.5 hours or more than 6.5 hours a night reported significant cognitive decline over time, but cognitive scores for those with sleep duration in between that range remained stable.
“This really suggests that there’s this middle range, a ‘sweet spot,’ where your sleep is really optimal,” said lead author Brendan Lucey, MD, MSCI, associate professor of neurology and director of the Washington University Sleep Medicine Center, St. Louis.
The study, published online Oct. 20 in Brain, is part of a growing body of research that seeks to determine if sleep can be used as a marker of Alzheimer’s disease progression.
A complex relationship
Studies suggest a strong relationship between sleep patterns and Alzheimer’s disease, which affects nearly 6 million Americans. The challenge, Dr. Lucey said, is unwinding the complex links between sleep, Alzheimer’s disease, and cognitive function.
An earlier study by Dr. Lucey and colleagues found that poor sleep quality is associated with early signs of Alzheimer’s disease, and a report published in September found that elderly people who slept less than 6 hours a night had a greater burden of amyloid beta, a hallmark sign of Alzheimer’s disease.
For this new study, researchers monitored sleep-wake activity over 4-6 nights in 100 participants who underwent annual cognitive assessments and clinical studies, including APOE genotyping, as part of a longitudinal study at the Knight Alzheimer Disease Research Center at Washington University. Participants also provided cerebrospinal fluid (CSF) total tau and amyloid-beta42 and wore a small EEG device on their forehead while they slept.
The majority of participants had a clinical dementia rating (CDR) score of 0, indicating no cognitive impairment. Twelve individuals had a CDR >0, with most reporting mild cognitive impairment.
As expected, CSF analysis showed greater evidence of Alzheimer’s disease pathology in those with a baseline CDR greater than 0.
Changes in cognitive function were measured using a Preclinical Alzheimer Cognitive Composite (PACC) score, a composite of results from a neuropsychological testing battery that included the Free and Cued Selective Reminding Test, the Logical Memory Delayed Recall Test from the Wechsler Memory Scale-Revised, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale-Revised, and the Mini-Mental State Examination.
Researchers found an upside-down U-shaped relationship between PACC scores and sleep duration, with dramatic cognitive decline in those who slept less than 4.5 hours or more than 6.5 hours a night (P < .001 for both). The U-shaped relationship was also found with measures of sleep phases, including time spent in rapid eye movement and in non-REM sleep (P < .001 for both).
The findings persisted even after controlling for confounders that can affect sleep and cognition, such as age, CSF total tau/amyloid-beta-42 ratio, APOE ε4 allele carrier status, years of education, and sex.
Understanding how sleep changes at different stages of Alzheimer’s disease could help researchers determine if sleep can be used as a marker of disease progression, Dr. Lucey said. That could lead to interventions to slow that process.
“We’re not at the point yet where we can say that we need to monitor someone’s sleep time and then do an intervention to see if it would improve their risk for cognitive decline,” said Dr. Lucey, who plans to repeat this sleep study with the same cohort to track changes in sleep patterns and cognitive function over time. “But that’s a question I’m very excited to try to answer.”
A component of cognitive health
Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, noted that the study adds to a body of evidence linking sleep and cognition, especially how sleep quality can optimize brain function.
“We’ve seen previous research that’s shown poor sleep contributes to dementia risk, as well as research showing sleep duration may play a role in cognition,” she said.
“We also need studies that look at sleep as an intervention for cognitive health,” Dr. Snyder said. “Sleep is an important aspect of our overall health. Clinicians should have conversations with their patients about sleep as part of standard discussions about their health habits and wellness.”
The study was funded by the National Institutes of Health, the American Sleep Medicine Foundation, the Roger and Paula Riney Fund, and the Daniel J. Brennan, MD Fund. Dr. Lucey consults for Merck and Eli Lilly. Dr. Snyder has disclosed no relevant financial relationships. Full disclosures are included in the original article.
A version of this article first appeared on Medscape.com.
In a longitudinal study, investigators found older adults who slept less than 4.5 hours or more than 6.5 hours a night reported significant cognitive decline over time, but cognitive scores for those with sleep duration in between that range remained stable.
“This really suggests that there’s this middle range, a ‘sweet spot,’ where your sleep is really optimal,” said lead author Brendan Lucey, MD, MSCI, associate professor of neurology and director of the Washington University Sleep Medicine Center, St. Louis.
The study, published online Oct. 20 in Brain, is part of a growing body of research that seeks to determine if sleep can be used as a marker of Alzheimer’s disease progression.
A complex relationship
Studies suggest a strong relationship between sleep patterns and Alzheimer’s disease, which affects nearly 6 million Americans. The challenge, Dr. Lucey said, is unwinding the complex links between sleep, Alzheimer’s disease, and cognitive function.
An earlier study by Dr. Lucey and colleagues found that poor sleep quality is associated with early signs of Alzheimer’s disease, and a report published in September found that elderly people who slept less than 6 hours a night had a greater burden of amyloid beta, a hallmark sign of Alzheimer’s disease.
For this new study, researchers monitored sleep-wake activity over 4-6 nights in 100 participants who underwent annual cognitive assessments and clinical studies, including APOE genotyping, as part of a longitudinal study at the Knight Alzheimer Disease Research Center at Washington University. Participants also provided cerebrospinal fluid (CSF) total tau and amyloid-beta42 and wore a small EEG device on their forehead while they slept.
The majority of participants had a clinical dementia rating (CDR) score of 0, indicating no cognitive impairment. Twelve individuals had a CDR >0, with most reporting mild cognitive impairment.
As expected, CSF analysis showed greater evidence of Alzheimer’s disease pathology in those with a baseline CDR greater than 0.
Changes in cognitive function were measured using a Preclinical Alzheimer Cognitive Composite (PACC) score, a composite of results from a neuropsychological testing battery that included the Free and Cued Selective Reminding Test, the Logical Memory Delayed Recall Test from the Wechsler Memory Scale-Revised, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale-Revised, and the Mini-Mental State Examination.
Researchers found an upside-down U-shaped relationship between PACC scores and sleep duration, with dramatic cognitive decline in those who slept less than 4.5 hours or more than 6.5 hours a night (P < .001 for both). The U-shaped relationship was also found with measures of sleep phases, including time spent in rapid eye movement and in non-REM sleep (P < .001 for both).
The findings persisted even after controlling for confounders that can affect sleep and cognition, such as age, CSF total tau/amyloid-beta-42 ratio, APOE ε4 allele carrier status, years of education, and sex.
Understanding how sleep changes at different stages of Alzheimer’s disease could help researchers determine if sleep can be used as a marker of disease progression, Dr. Lucey said. That could lead to interventions to slow that process.
“We’re not at the point yet where we can say that we need to monitor someone’s sleep time and then do an intervention to see if it would improve their risk for cognitive decline,” said Dr. Lucey, who plans to repeat this sleep study with the same cohort to track changes in sleep patterns and cognitive function over time. “But that’s a question I’m very excited to try to answer.”
A component of cognitive health
Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, noted that the study adds to a body of evidence linking sleep and cognition, especially how sleep quality can optimize brain function.
“We’ve seen previous research that’s shown poor sleep contributes to dementia risk, as well as research showing sleep duration may play a role in cognition,” she said.
“We also need studies that look at sleep as an intervention for cognitive health,” Dr. Snyder said. “Sleep is an important aspect of our overall health. Clinicians should have conversations with their patients about sleep as part of standard discussions about their health habits and wellness.”
The study was funded by the National Institutes of Health, the American Sleep Medicine Foundation, the Roger and Paula Riney Fund, and the Daniel J. Brennan, MD Fund. Dr. Lucey consults for Merck and Eli Lilly. Dr. Snyder has disclosed no relevant financial relationships. Full disclosures are included in the original article.
A version of this article first appeared on Medscape.com.
In a longitudinal study, investigators found older adults who slept less than 4.5 hours or more than 6.5 hours a night reported significant cognitive decline over time, but cognitive scores for those with sleep duration in between that range remained stable.
“This really suggests that there’s this middle range, a ‘sweet spot,’ where your sleep is really optimal,” said lead author Brendan Lucey, MD, MSCI, associate professor of neurology and director of the Washington University Sleep Medicine Center, St. Louis.
The study, published online Oct. 20 in Brain, is part of a growing body of research that seeks to determine if sleep can be used as a marker of Alzheimer’s disease progression.
A complex relationship
Studies suggest a strong relationship between sleep patterns and Alzheimer’s disease, which affects nearly 6 million Americans. The challenge, Dr. Lucey said, is unwinding the complex links between sleep, Alzheimer’s disease, and cognitive function.
An earlier study by Dr. Lucey and colleagues found that poor sleep quality is associated with early signs of Alzheimer’s disease, and a report published in September found that elderly people who slept less than 6 hours a night had a greater burden of amyloid beta, a hallmark sign of Alzheimer’s disease.
For this new study, researchers monitored sleep-wake activity over 4-6 nights in 100 participants who underwent annual cognitive assessments and clinical studies, including APOE genotyping, as part of a longitudinal study at the Knight Alzheimer Disease Research Center at Washington University. Participants also provided cerebrospinal fluid (CSF) total tau and amyloid-beta42 and wore a small EEG device on their forehead while they slept.
The majority of participants had a clinical dementia rating (CDR) score of 0, indicating no cognitive impairment. Twelve individuals had a CDR >0, with most reporting mild cognitive impairment.
As expected, CSF analysis showed greater evidence of Alzheimer’s disease pathology in those with a baseline CDR greater than 0.
Changes in cognitive function were measured using a Preclinical Alzheimer Cognitive Composite (PACC) score, a composite of results from a neuropsychological testing battery that included the Free and Cued Selective Reminding Test, the Logical Memory Delayed Recall Test from the Wechsler Memory Scale-Revised, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale-Revised, and the Mini-Mental State Examination.
Researchers found an upside-down U-shaped relationship between PACC scores and sleep duration, with dramatic cognitive decline in those who slept less than 4.5 hours or more than 6.5 hours a night (P < .001 for both). The U-shaped relationship was also found with measures of sleep phases, including time spent in rapid eye movement and in non-REM sleep (P < .001 for both).
The findings persisted even after controlling for confounders that can affect sleep and cognition, such as age, CSF total tau/amyloid-beta-42 ratio, APOE ε4 allele carrier status, years of education, and sex.
Understanding how sleep changes at different stages of Alzheimer’s disease could help researchers determine if sleep can be used as a marker of disease progression, Dr. Lucey said. That could lead to interventions to slow that process.
“We’re not at the point yet where we can say that we need to monitor someone’s sleep time and then do an intervention to see if it would improve their risk for cognitive decline,” said Dr. Lucey, who plans to repeat this sleep study with the same cohort to track changes in sleep patterns and cognitive function over time. “But that’s a question I’m very excited to try to answer.”
A component of cognitive health
Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, noted that the study adds to a body of evidence linking sleep and cognition, especially how sleep quality can optimize brain function.
“We’ve seen previous research that’s shown poor sleep contributes to dementia risk, as well as research showing sleep duration may play a role in cognition,” she said.
“We also need studies that look at sleep as an intervention for cognitive health,” Dr. Snyder said. “Sleep is an important aspect of our overall health. Clinicians should have conversations with their patients about sleep as part of standard discussions about their health habits and wellness.”
The study was funded by the National Institutes of Health, the American Sleep Medicine Foundation, the Roger and Paula Riney Fund, and the Daniel J. Brennan, MD Fund. Dr. Lucey consults for Merck and Eli Lilly. Dr. Snyder has disclosed no relevant financial relationships. Full disclosures are included in the original article.
A version of this article first appeared on Medscape.com.
From Brain
AAN blasts ‘runaway’ costs for neurologic and other prescription drugs
This situation is also taking a toll on neurologists’ mental health, who already have the second-highest burnout rate across medical specialties, the statement adds.
The statement was published online Oct. 5, 2021, in Neurology.
Dramatic price increases
Drafted by the Ethics, Law, and Humanities Committee – a joint committee that includes the AAN, the American Neurological Association, and the Child Neurology Society – the statement was prompted by a 2018 report from the AAN Neurology Drug Pricing Task Force to address challenges associated with high drug costs.
It highlights ethical concerns from high drug costs, policy proposals that might temper the problem, and how clinicians can adjust to the current reality of pharmaceutical pricing and better advocate for changes to the healthcare system.
“Runaway drug costs continue to be a pressing problem with recent dramatic price increases not only for specialty drugs, but also generic ones,” said lead author Amy Tsou, MD, MSc, codirector of the ECRI Evidence-Based Practice Center at the Center for Evidence and Guidelines in Plymouth Meeting, Pa.
She noted that one in four Americans has difficulty paying for medication, and many report going without a medication because of cost.
“Ensuring a fair system for drug pricing and coverage rules that balance the goods of individual patients with the needs of broader populations when resources are limited remains more important than ever,” Dr. Tsou said.
Out-of-pocket costs for neurologic medications have risen dramatically over the past decade, with the fastest rise reported among drugs for multiple sclerosis. Results from a study published in 2019 showed that, between 2004 and 2016, patients’ out-of-pocket expenses skyrocketed from $15 a month to $309 a month.
The steep increases have forced some neurology patients to ration their medication or stop taking it altogether, which is one of the ethical concerns cited in the AAN statement.
Patient self-rationing
Commenting on the statement, Ilana Katz Sand, MD, associate director of the Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center, New York, noted that clinicians are already acutely aware of the effect high drug costs have on their patients’ medical decisions. However, statements such as the current one bring much-needed outside attention to the problem.
“I’ve definitely had more and more people struggling with deductibles and copays, even among people who are insured,” said Dr. Katz Sand, who was not involved with the AAN paper.
She has a number of patients who have rationed their medication or stopped taking it altogether when their copays increased or they lost access to a copay assistance program because their insurance company chose to cover a still-expensive generic drug with no assistance program over a slightly costlier brand-name medication that comes with patient discounts.
Too often, patients don’t tell her they’re not taking their medication as prescribed. At a recent appointment, Dr. Katz Sand learned about a patient’s drug rationing only after a routine MRI showed new brain lesions that regular treatment might have prevented.
Another patient, new to her clinic, questioned the treatment plan Dr. Katz Sand recommended because they could not cover the copay. This sort of self-rationing happens in patients with and without insurance, she added.
“It’s a terrible thing and it’s happening to all patients,” Dr. Katz Sand said, adding that “the old credo of ‘yeah, the drug prices are high, but they are covered by insurance’ is not a sustainable argument anymore.”
What neurologists can do
Some sort of rationing is an unavoidable outcome of steep treatment costs, the authors noted. But what does that mean in clinical practice?
Neurologists should be aware of the costs involved in ordering diagnostic tests, treatment, or medication – and shouldn’t feel compelled to order treatments or tests that they feel are medically inappropriate just because a patient requests them, the authors wrote.
The statement also encourages clinicians to include financial realities in the shared decision-making process with patients.
However, Dr. Katz Sand said that is not always possible. Drug prices aren’t fixed, with different insurance plans offering different pricing, deductibles, and copays. “It’s hard for us to attempt to incorporate discussions about price in our discussions with patients when we can’t even predict what their out-of-pocket cost is going to be,” she said.
“Every single prescription we write requires prior authorization, and that’s directly related to the fact that the cost of these drugs is so high,” she added.
As do many other clinicians, Dr. Katz Sand spends hours each week on preauthorization forms and haggling with insurance companies on behalf of her patients. To get needed medication at a cost they can afford sometimes takes creative problem solving and almost always takes a lot of time. “It all adds to the administrative burden, patients’ stress, and our stress,” she said.
Physician-advocates needed
The AAN paper identifies a number of policy reforms to address drug pricing at a national level, including giving Medicare officials the power to negotiate drug prices, allowing the safe importation of drugs from other countries, and speeding the Food and Drug Administration approval process for generic drugs.
There is also a need to address systemic problems that, the authors noted, help create and perpetuate health care disparities. Lawmakers at the state and federal level are considering a number of these policy ideas and others that could address the kinds of issues Dr. Katz Sand described. However, the chances of their success are slim at best, said Bruce H. Cohen, MD, chair of the AAN advocacy committee and director of the NeuroDevelopmental Science Center at Akron (Ohio) Children’s Hospital.
“On a federal level, we’re watching in real time how the entrenched divisions, even within parties, are resulting in continued stalemate,” said Dr. Cohen, who is not one of the statement authors.
Those ideas need advocates and the AAN paper suggests neurologists should be among the ones championing these changes, he added.
“One of the most effective strategies is to bring attention to the impact high drug costs have on neurology patients and medical practices,” Dr. Cohen said. “It’s so important to make sure policy makers know the significant impact of high drug costs in neurology and within the context of finite resources.”
One way to do that is to share statements such as the current one with members of Congress working on policy reform, Dr. Cohen said. Another is through programs such as the academy’s annual Neurology on the Hill conference.
A third strategy is to encourage individuals such as Dr. Katz Sand to speak out when and where they can, he added.
While she agrees with the idea, finding time for advocacy work amid patient care, administrative work, and research is challenging. Dr. Katz Sand would like to see groups like the AAN work with health care institutions to implement policies that allocate time and resources to train clinicians in advocacy – and then support their efforts on that front.
“I’m really glad they wrote this and think they did a good job of crystallizing the issues,” Dr. Katz Sand said. “It’s good to put it out there as a document that could help serve as the basis for the requests we make collectively. I just hope that people listen.”
The paper received no funding. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This situation is also taking a toll on neurologists’ mental health, who already have the second-highest burnout rate across medical specialties, the statement adds.
The statement was published online Oct. 5, 2021, in Neurology.
Dramatic price increases
Drafted by the Ethics, Law, and Humanities Committee – a joint committee that includes the AAN, the American Neurological Association, and the Child Neurology Society – the statement was prompted by a 2018 report from the AAN Neurology Drug Pricing Task Force to address challenges associated with high drug costs.
It highlights ethical concerns from high drug costs, policy proposals that might temper the problem, and how clinicians can adjust to the current reality of pharmaceutical pricing and better advocate for changes to the healthcare system.
“Runaway drug costs continue to be a pressing problem with recent dramatic price increases not only for specialty drugs, but also generic ones,” said lead author Amy Tsou, MD, MSc, codirector of the ECRI Evidence-Based Practice Center at the Center for Evidence and Guidelines in Plymouth Meeting, Pa.
She noted that one in four Americans has difficulty paying for medication, and many report going without a medication because of cost.
“Ensuring a fair system for drug pricing and coverage rules that balance the goods of individual patients with the needs of broader populations when resources are limited remains more important than ever,” Dr. Tsou said.
Out-of-pocket costs for neurologic medications have risen dramatically over the past decade, with the fastest rise reported among drugs for multiple sclerosis. Results from a study published in 2019 showed that, between 2004 and 2016, patients’ out-of-pocket expenses skyrocketed from $15 a month to $309 a month.
The steep increases have forced some neurology patients to ration their medication or stop taking it altogether, which is one of the ethical concerns cited in the AAN statement.
Patient self-rationing
Commenting on the statement, Ilana Katz Sand, MD, associate director of the Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center, New York, noted that clinicians are already acutely aware of the effect high drug costs have on their patients’ medical decisions. However, statements such as the current one bring much-needed outside attention to the problem.
“I’ve definitely had more and more people struggling with deductibles and copays, even among people who are insured,” said Dr. Katz Sand, who was not involved with the AAN paper.
She has a number of patients who have rationed their medication or stopped taking it altogether when their copays increased or they lost access to a copay assistance program because their insurance company chose to cover a still-expensive generic drug with no assistance program over a slightly costlier brand-name medication that comes with patient discounts.
Too often, patients don’t tell her they’re not taking their medication as prescribed. At a recent appointment, Dr. Katz Sand learned about a patient’s drug rationing only after a routine MRI showed new brain lesions that regular treatment might have prevented.
Another patient, new to her clinic, questioned the treatment plan Dr. Katz Sand recommended because they could not cover the copay. This sort of self-rationing happens in patients with and without insurance, she added.
“It’s a terrible thing and it’s happening to all patients,” Dr. Katz Sand said, adding that “the old credo of ‘yeah, the drug prices are high, but they are covered by insurance’ is not a sustainable argument anymore.”
What neurologists can do
Some sort of rationing is an unavoidable outcome of steep treatment costs, the authors noted. But what does that mean in clinical practice?
Neurologists should be aware of the costs involved in ordering diagnostic tests, treatment, or medication – and shouldn’t feel compelled to order treatments or tests that they feel are medically inappropriate just because a patient requests them, the authors wrote.
The statement also encourages clinicians to include financial realities in the shared decision-making process with patients.
However, Dr. Katz Sand said that is not always possible. Drug prices aren’t fixed, with different insurance plans offering different pricing, deductibles, and copays. “It’s hard for us to attempt to incorporate discussions about price in our discussions with patients when we can’t even predict what their out-of-pocket cost is going to be,” she said.
“Every single prescription we write requires prior authorization, and that’s directly related to the fact that the cost of these drugs is so high,” she added.
As do many other clinicians, Dr. Katz Sand spends hours each week on preauthorization forms and haggling with insurance companies on behalf of her patients. To get needed medication at a cost they can afford sometimes takes creative problem solving and almost always takes a lot of time. “It all adds to the administrative burden, patients’ stress, and our stress,” she said.
Physician-advocates needed
The AAN paper identifies a number of policy reforms to address drug pricing at a national level, including giving Medicare officials the power to negotiate drug prices, allowing the safe importation of drugs from other countries, and speeding the Food and Drug Administration approval process for generic drugs.
There is also a need to address systemic problems that, the authors noted, help create and perpetuate health care disparities. Lawmakers at the state and federal level are considering a number of these policy ideas and others that could address the kinds of issues Dr. Katz Sand described. However, the chances of their success are slim at best, said Bruce H. Cohen, MD, chair of the AAN advocacy committee and director of the NeuroDevelopmental Science Center at Akron (Ohio) Children’s Hospital.
“On a federal level, we’re watching in real time how the entrenched divisions, even within parties, are resulting in continued stalemate,” said Dr. Cohen, who is not one of the statement authors.
Those ideas need advocates and the AAN paper suggests neurologists should be among the ones championing these changes, he added.
“One of the most effective strategies is to bring attention to the impact high drug costs have on neurology patients and medical practices,” Dr. Cohen said. “It’s so important to make sure policy makers know the significant impact of high drug costs in neurology and within the context of finite resources.”
One way to do that is to share statements such as the current one with members of Congress working on policy reform, Dr. Cohen said. Another is through programs such as the academy’s annual Neurology on the Hill conference.
A third strategy is to encourage individuals such as Dr. Katz Sand to speak out when and where they can, he added.
While she agrees with the idea, finding time for advocacy work amid patient care, administrative work, and research is challenging. Dr. Katz Sand would like to see groups like the AAN work with health care institutions to implement policies that allocate time and resources to train clinicians in advocacy – and then support their efforts on that front.
“I’m really glad they wrote this and think they did a good job of crystallizing the issues,” Dr. Katz Sand said. “It’s good to put it out there as a document that could help serve as the basis for the requests we make collectively. I just hope that people listen.”
The paper received no funding. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This situation is also taking a toll on neurologists’ mental health, who already have the second-highest burnout rate across medical specialties, the statement adds.
The statement was published online Oct. 5, 2021, in Neurology.
Dramatic price increases
Drafted by the Ethics, Law, and Humanities Committee – a joint committee that includes the AAN, the American Neurological Association, and the Child Neurology Society – the statement was prompted by a 2018 report from the AAN Neurology Drug Pricing Task Force to address challenges associated with high drug costs.
It highlights ethical concerns from high drug costs, policy proposals that might temper the problem, and how clinicians can adjust to the current reality of pharmaceutical pricing and better advocate for changes to the healthcare system.
“Runaway drug costs continue to be a pressing problem with recent dramatic price increases not only for specialty drugs, but also generic ones,” said lead author Amy Tsou, MD, MSc, codirector of the ECRI Evidence-Based Practice Center at the Center for Evidence and Guidelines in Plymouth Meeting, Pa.
She noted that one in four Americans has difficulty paying for medication, and many report going without a medication because of cost.
“Ensuring a fair system for drug pricing and coverage rules that balance the goods of individual patients with the needs of broader populations when resources are limited remains more important than ever,” Dr. Tsou said.
Out-of-pocket costs for neurologic medications have risen dramatically over the past decade, with the fastest rise reported among drugs for multiple sclerosis. Results from a study published in 2019 showed that, between 2004 and 2016, patients’ out-of-pocket expenses skyrocketed from $15 a month to $309 a month.
The steep increases have forced some neurology patients to ration their medication or stop taking it altogether, which is one of the ethical concerns cited in the AAN statement.
Patient self-rationing
Commenting on the statement, Ilana Katz Sand, MD, associate director of the Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center, New York, noted that clinicians are already acutely aware of the effect high drug costs have on their patients’ medical decisions. However, statements such as the current one bring much-needed outside attention to the problem.
“I’ve definitely had more and more people struggling with deductibles and copays, even among people who are insured,” said Dr. Katz Sand, who was not involved with the AAN paper.
She has a number of patients who have rationed their medication or stopped taking it altogether when their copays increased or they lost access to a copay assistance program because their insurance company chose to cover a still-expensive generic drug with no assistance program over a slightly costlier brand-name medication that comes with patient discounts.
Too often, patients don’t tell her they’re not taking their medication as prescribed. At a recent appointment, Dr. Katz Sand learned about a patient’s drug rationing only after a routine MRI showed new brain lesions that regular treatment might have prevented.
Another patient, new to her clinic, questioned the treatment plan Dr. Katz Sand recommended because they could not cover the copay. This sort of self-rationing happens in patients with and without insurance, she added.
“It’s a terrible thing and it’s happening to all patients,” Dr. Katz Sand said, adding that “the old credo of ‘yeah, the drug prices are high, but they are covered by insurance’ is not a sustainable argument anymore.”
What neurologists can do
Some sort of rationing is an unavoidable outcome of steep treatment costs, the authors noted. But what does that mean in clinical practice?
Neurologists should be aware of the costs involved in ordering diagnostic tests, treatment, or medication – and shouldn’t feel compelled to order treatments or tests that they feel are medically inappropriate just because a patient requests them, the authors wrote.
The statement also encourages clinicians to include financial realities in the shared decision-making process with patients.
However, Dr. Katz Sand said that is not always possible. Drug prices aren’t fixed, with different insurance plans offering different pricing, deductibles, and copays. “It’s hard for us to attempt to incorporate discussions about price in our discussions with patients when we can’t even predict what their out-of-pocket cost is going to be,” she said.
“Every single prescription we write requires prior authorization, and that’s directly related to the fact that the cost of these drugs is so high,” she added.
As do many other clinicians, Dr. Katz Sand spends hours each week on preauthorization forms and haggling with insurance companies on behalf of her patients. To get needed medication at a cost they can afford sometimes takes creative problem solving and almost always takes a lot of time. “It all adds to the administrative burden, patients’ stress, and our stress,” she said.
Physician-advocates needed
The AAN paper identifies a number of policy reforms to address drug pricing at a national level, including giving Medicare officials the power to negotiate drug prices, allowing the safe importation of drugs from other countries, and speeding the Food and Drug Administration approval process for generic drugs.
There is also a need to address systemic problems that, the authors noted, help create and perpetuate health care disparities. Lawmakers at the state and federal level are considering a number of these policy ideas and others that could address the kinds of issues Dr. Katz Sand described. However, the chances of their success are slim at best, said Bruce H. Cohen, MD, chair of the AAN advocacy committee and director of the NeuroDevelopmental Science Center at Akron (Ohio) Children’s Hospital.
“On a federal level, we’re watching in real time how the entrenched divisions, even within parties, are resulting in continued stalemate,” said Dr. Cohen, who is not one of the statement authors.
Those ideas need advocates and the AAN paper suggests neurologists should be among the ones championing these changes, he added.
“One of the most effective strategies is to bring attention to the impact high drug costs have on neurology patients and medical practices,” Dr. Cohen said. “It’s so important to make sure policy makers know the significant impact of high drug costs in neurology and within the context of finite resources.”
One way to do that is to share statements such as the current one with members of Congress working on policy reform, Dr. Cohen said. Another is through programs such as the academy’s annual Neurology on the Hill conference.
A third strategy is to encourage individuals such as Dr. Katz Sand to speak out when and where they can, he added.
While she agrees with the idea, finding time for advocacy work amid patient care, administrative work, and research is challenging. Dr. Katz Sand would like to see groups like the AAN work with health care institutions to implement policies that allocate time and resources to train clinicians in advocacy – and then support their efforts on that front.
“I’m really glad they wrote this and think they did a good job of crystallizing the issues,” Dr. Katz Sand said. “It’s good to put it out there as a document that could help serve as the basis for the requests we make collectively. I just hope that people listen.”
The paper received no funding. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Is AFib a stroke cause or innocent bystander? The debate continues
Discovery of substantial atrial fibrillation (AFib) is usually an indication to start oral anticoagulation (OAC) for stroke prevention, but it’s far from settled whether such AFib is actually a direct cause of thromboembolic stroke. And that has implications for whether patients with occasional bouts of the arrhythmia need to be on continuous OAC.
It’s possible that some with infrequent paroxysmal AFib can get away with OAC maintained only about as long as the arrhythmia persists, and then go off the drugs, say researchers based on their study, which, they caution, would need the support of prospective trials before such a strategy could be considered.
But importantly, in their patients who had been continuously monitored by their cardiac implantable electronic devices (CIEDs) prior to experiencing a stroke, the 30-day risk of that stroke more than tripled if their AFib burden on 1 day reached at least 5-6 hours. The risk jumped especially high within the first few days after accumulating that amount of AFib in a day, but then fell off sharply over the next few days.
Based on the study, “Your risk of stroke goes up acutely when you have an episode of AFib, and it decreases rapidly, back to baseline – certainly by 30 days and it looked like in our data by 5 days,” Daniel E. Singer, MD, of Massachusetts General Hospital, Boston, said in an interview.
Increasingly, he noted, “there’s a widespread belief that AFib is a risk marker, not a causal risk factor.” In that scenario, most embolic strokes are caused by thrombi formed as a result of an atrial myopathy, characterized by fibrosis and inflammation, that also happens to trigger AFib.
But said Dr. Singer, who is lead author on the analysis published online Sept. 29 in JAMA Cardiology.
Some studies have “shown that anticoagulants seem to lower stroke risk even in patients without atrial fib, and even from sources not likely to be coming from the atrium,” Mintu P. Turakhia, MD, of Stanford (Calif.) University, Palo Alto, said in an interview. Collectively they point to “atrial fibrillation as a cause of and a noncausal marker for stroke.”
For example, Dr. Turakhia pointed out in an editorial accompanying the current report that stroke in patients with CIEDs “may occur during prolonged periods of sinus rhythm.”
The current study, he said in an interview, doesn’t preclude atrial myopathy as one direct cause of stroke-associated thrombus, because probably both the myopathy and AFib can be culprits. Still, AFib itself it may bear more responsibility for strokes in patients with fewer competing risks for stroke.
In such patients at lower vascular risk, who may have a CHA2DS2-VASc score of only 1 or 2, for example, “AFib can become a more important cause” of ischemic stroke, Dr. Turakhia said. That’s when AFib is more likely to be temporally related to stroke as the likely culprit, the mechanism addressed by Dr. Singer and associates.
“I think we’re all trying to grapple with what the truth is,” Dr. Singer observed. Still, the current study was unusual for primarily looking at the temporal relationship between AFib and stroke, rather than stroke risk. “And once again, as we found in our earlier study, but now a much larger study, it’s a tight relationship.”
Based on the current results, he said, the risk is “high when you have AFib, and it decreases very rapidly after the AFib is over.” And, “it takes multiple hours of AFib to raise stroke risk.” Inclusion in the analysis required accumulation of at least 5.5 hours of AFib on at least 1 day in a month, the cut point at which stroke risk started to climb significantly in an earlier trial.
In the current analysis, however, the 30-day odds ratio for stroke was a nonsignificant 2.75 for an AFib burden of 6-23 hours in a day and jumped to a significant 5.0 for a burden in excess of 23 hours in a day. “That’s a lot of AFib” before the risk actually goes up, and supports AFib as causative, Dr. Singer said. If it were the myopathy itself triggering stroke in these particular patients, the risk would be ongoing and not subject to a threshold of AFib burden.
Implications for noncontinuous OAC
“The hope is that there are people who have very little AFib: They may have several hours, and then they have nothing for 6 months. Do they have to be anticoagulated or not?” Dr. Singer asked.
“If you believe the risk-marker story, you might say they have to be anticoagulated. But if you believe our results, you would certainly think there’s a good chance they don’t have to be anticoagulated,” he said.
“So it is logical to think, if you have the right people and continuous monitoring, that you could have time-delimited anticoagulation.” That is, patients might start right away on a direct OAC once reaching the AFib threshold in a day, Dr. Singer said, “going on and off anticoagulants in parallel with their episodes of AFib.”
The strategy wouldn’t be feasible in patients who often experience AFib, Dr. Singer noted, “but it might work for people who have infrequent paroxysmal AFib.” It certainly would first have to be tested in prospective trials, he said. Such trials would be more practical than ever to carry out given the growing availability of continuous AFib monitoring by wearables.
“We need a trial to make the case whether it’s safe or not,” Dr. Turakhia said of such a rhythm-guided approach to OAC for AFib. The population to start with, he said, would be patients with paroxysmal AFib and low CHA2DS2-VASc scores. “If you think CHA2DS2-VASc as an integrated score of vascular risk, such patients would have a lot fewer reasons to have strokes. And if they do have a stroke, it’s more reasonable to assume that it’s likely caused by atrial fib and not just a marker.”
Importantly, such a strategy could well be safer than continuous OAC for some patients – those at the lowest vascular risk and with the most occasional AFib and lowest AFib burden “who are otherwise doing fine,” Dr. Turakhia said. In such patients on continuous OAC, he proposed, the risks of bleeding and intracranial hemorrhage could potentially exceed the expected degree of protection from ischemic events.
Discordant periods of AFib burden
Dr. Singer and his colleagues linked a national electronic health record database with Medtronic CareLink records covering 10 years to identify 891 patients who experienced an ischemic stroke preceded by at least 120 days of continuous heart-rhythm monitoring.
The patients were then categorized by their pattern of AFib, if any, within each of two prestroke periods: the most recent 30 days, which was the test period, and the preceding 91-120 days, the control period.
The analysis then excluded any patients who reached an AFib-burden threshold of at least 5.5 hours on any day during both the test and control periods, and those who did not attain that threshold in either period.
“The ones who had AFib in both periods mostly had permanent AFib, and ones that didn’t have AFib in either period mostly were in sinus rhythm,” Dr. Singer said. It was “close to 100%” in both cases.
Those exclusions left 66 patients, 7.4% of the total, who reached the AFib-burden threshold on at least 1 day during either the test or control periods, but not both. They included 52 and 14 patients, respectively, with “discordant” periods, that is, at least that burden of AFib in a day during either the test or control period, but not both.
Comparing AFib burden at test versus control periods among patients for whom the two periods were discordant yielded an OR for stroke of 3.71 (95% confidence interval, 2.06-6.70).
Stroke risk levels were not evenly spread throughout the 24-hour periods that met the AFib-burden threshold or the 30 days preceding the patients’ strokes. The OR for stroke was 5.00 (95% CI, 2.62-9.55) during days 1-5 following the day in which the AFib-burden threshold was met. And it was 5.00 (95% CI, 2.08-12.01) over 30 days if the AFib burden exceeded 23 hours on any day of the test period.
The study’s case-crossover design, in which each patient served as their own control, is one of its advantages, Dr. Singer observed. Most patient features, including CHA2DS2-VASc score and comorbidities, did not change appreciably from earliest to the latest 30-day period, which strengthens the comparison of the two because “you don’t have to worry about long-term confounding.”
Dr. Singer was supported by the Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital. He discloses receiving grants from Boehringer Ingelheim and Bristol-Myers Squibb; personal fees from Boehringer Ingelheim, Bristol-Myers Squibb, Fitbit, Johnson & Johnson, Merck, and Pfizer; and royalties from UpToDate.
Dr. Turakhia discloses personal fees from Medtronic, Abbott, Sanofi, Pfizer, Myokardia, Johnson & Johnson, Milestone Pharmaceuticals, InCarda Therapeutics, 100Plus, Forward Pharma, and AliveCor; and grants from Bristol-Myers Squibb, the American Heart Association, Apple, and Bayer.
A version of this article first appeared on Medscape.com.
Discovery of substantial atrial fibrillation (AFib) is usually an indication to start oral anticoagulation (OAC) for stroke prevention, but it’s far from settled whether such AFib is actually a direct cause of thromboembolic stroke. And that has implications for whether patients with occasional bouts of the arrhythmia need to be on continuous OAC.
It’s possible that some with infrequent paroxysmal AFib can get away with OAC maintained only about as long as the arrhythmia persists, and then go off the drugs, say researchers based on their study, which, they caution, would need the support of prospective trials before such a strategy could be considered.
But importantly, in their patients who had been continuously monitored by their cardiac implantable electronic devices (CIEDs) prior to experiencing a stroke, the 30-day risk of that stroke more than tripled if their AFib burden on 1 day reached at least 5-6 hours. The risk jumped especially high within the first few days after accumulating that amount of AFib in a day, but then fell off sharply over the next few days.
Based on the study, “Your risk of stroke goes up acutely when you have an episode of AFib, and it decreases rapidly, back to baseline – certainly by 30 days and it looked like in our data by 5 days,” Daniel E. Singer, MD, of Massachusetts General Hospital, Boston, said in an interview.
Increasingly, he noted, “there’s a widespread belief that AFib is a risk marker, not a causal risk factor.” In that scenario, most embolic strokes are caused by thrombi formed as a result of an atrial myopathy, characterized by fibrosis and inflammation, that also happens to trigger AFib.
But said Dr. Singer, who is lead author on the analysis published online Sept. 29 in JAMA Cardiology.
Some studies have “shown that anticoagulants seem to lower stroke risk even in patients without atrial fib, and even from sources not likely to be coming from the atrium,” Mintu P. Turakhia, MD, of Stanford (Calif.) University, Palo Alto, said in an interview. Collectively they point to “atrial fibrillation as a cause of and a noncausal marker for stroke.”
For example, Dr. Turakhia pointed out in an editorial accompanying the current report that stroke in patients with CIEDs “may occur during prolonged periods of sinus rhythm.”
The current study, he said in an interview, doesn’t preclude atrial myopathy as one direct cause of stroke-associated thrombus, because probably both the myopathy and AFib can be culprits. Still, AFib itself it may bear more responsibility for strokes in patients with fewer competing risks for stroke.
In such patients at lower vascular risk, who may have a CHA2DS2-VASc score of only 1 or 2, for example, “AFib can become a more important cause” of ischemic stroke, Dr. Turakhia said. That’s when AFib is more likely to be temporally related to stroke as the likely culprit, the mechanism addressed by Dr. Singer and associates.
“I think we’re all trying to grapple with what the truth is,” Dr. Singer observed. Still, the current study was unusual for primarily looking at the temporal relationship between AFib and stroke, rather than stroke risk. “And once again, as we found in our earlier study, but now a much larger study, it’s a tight relationship.”
Based on the current results, he said, the risk is “high when you have AFib, and it decreases very rapidly after the AFib is over.” And, “it takes multiple hours of AFib to raise stroke risk.” Inclusion in the analysis required accumulation of at least 5.5 hours of AFib on at least 1 day in a month, the cut point at which stroke risk started to climb significantly in an earlier trial.
In the current analysis, however, the 30-day odds ratio for stroke was a nonsignificant 2.75 for an AFib burden of 6-23 hours in a day and jumped to a significant 5.0 for a burden in excess of 23 hours in a day. “That’s a lot of AFib” before the risk actually goes up, and supports AFib as causative, Dr. Singer said. If it were the myopathy itself triggering stroke in these particular patients, the risk would be ongoing and not subject to a threshold of AFib burden.
Implications for noncontinuous OAC
“The hope is that there are people who have very little AFib: They may have several hours, and then they have nothing for 6 months. Do they have to be anticoagulated or not?” Dr. Singer asked.
“If you believe the risk-marker story, you might say they have to be anticoagulated. But if you believe our results, you would certainly think there’s a good chance they don’t have to be anticoagulated,” he said.
“So it is logical to think, if you have the right people and continuous monitoring, that you could have time-delimited anticoagulation.” That is, patients might start right away on a direct OAC once reaching the AFib threshold in a day, Dr. Singer said, “going on and off anticoagulants in parallel with their episodes of AFib.”
The strategy wouldn’t be feasible in patients who often experience AFib, Dr. Singer noted, “but it might work for people who have infrequent paroxysmal AFib.” It certainly would first have to be tested in prospective trials, he said. Such trials would be more practical than ever to carry out given the growing availability of continuous AFib monitoring by wearables.
“We need a trial to make the case whether it’s safe or not,” Dr. Turakhia said of such a rhythm-guided approach to OAC for AFib. The population to start with, he said, would be patients with paroxysmal AFib and low CHA2DS2-VASc scores. “If you think CHA2DS2-VASc as an integrated score of vascular risk, such patients would have a lot fewer reasons to have strokes. And if they do have a stroke, it’s more reasonable to assume that it’s likely caused by atrial fib and not just a marker.”
Importantly, such a strategy could well be safer than continuous OAC for some patients – those at the lowest vascular risk and with the most occasional AFib and lowest AFib burden “who are otherwise doing fine,” Dr. Turakhia said. In such patients on continuous OAC, he proposed, the risks of bleeding and intracranial hemorrhage could potentially exceed the expected degree of protection from ischemic events.
Discordant periods of AFib burden
Dr. Singer and his colleagues linked a national electronic health record database with Medtronic CareLink records covering 10 years to identify 891 patients who experienced an ischemic stroke preceded by at least 120 days of continuous heart-rhythm monitoring.
The patients were then categorized by their pattern of AFib, if any, within each of two prestroke periods: the most recent 30 days, which was the test period, and the preceding 91-120 days, the control period.
The analysis then excluded any patients who reached an AFib-burden threshold of at least 5.5 hours on any day during both the test and control periods, and those who did not attain that threshold in either period.
“The ones who had AFib in both periods mostly had permanent AFib, and ones that didn’t have AFib in either period mostly were in sinus rhythm,” Dr. Singer said. It was “close to 100%” in both cases.
Those exclusions left 66 patients, 7.4% of the total, who reached the AFib-burden threshold on at least 1 day during either the test or control periods, but not both. They included 52 and 14 patients, respectively, with “discordant” periods, that is, at least that burden of AFib in a day during either the test or control period, but not both.
Comparing AFib burden at test versus control periods among patients for whom the two periods were discordant yielded an OR for stroke of 3.71 (95% confidence interval, 2.06-6.70).
Stroke risk levels were not evenly spread throughout the 24-hour periods that met the AFib-burden threshold or the 30 days preceding the patients’ strokes. The OR for stroke was 5.00 (95% CI, 2.62-9.55) during days 1-5 following the day in which the AFib-burden threshold was met. And it was 5.00 (95% CI, 2.08-12.01) over 30 days if the AFib burden exceeded 23 hours on any day of the test period.
The study’s case-crossover design, in which each patient served as their own control, is one of its advantages, Dr. Singer observed. Most patient features, including CHA2DS2-VASc score and comorbidities, did not change appreciably from earliest to the latest 30-day period, which strengthens the comparison of the two because “you don’t have to worry about long-term confounding.”
Dr. Singer was supported by the Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital. He discloses receiving grants from Boehringer Ingelheim and Bristol-Myers Squibb; personal fees from Boehringer Ingelheim, Bristol-Myers Squibb, Fitbit, Johnson & Johnson, Merck, and Pfizer; and royalties from UpToDate.
Dr. Turakhia discloses personal fees from Medtronic, Abbott, Sanofi, Pfizer, Myokardia, Johnson & Johnson, Milestone Pharmaceuticals, InCarda Therapeutics, 100Plus, Forward Pharma, and AliveCor; and grants from Bristol-Myers Squibb, the American Heart Association, Apple, and Bayer.
A version of this article first appeared on Medscape.com.
Discovery of substantial atrial fibrillation (AFib) is usually an indication to start oral anticoagulation (OAC) for stroke prevention, but it’s far from settled whether such AFib is actually a direct cause of thromboembolic stroke. And that has implications for whether patients with occasional bouts of the arrhythmia need to be on continuous OAC.
It’s possible that some with infrequent paroxysmal AFib can get away with OAC maintained only about as long as the arrhythmia persists, and then go off the drugs, say researchers based on their study, which, they caution, would need the support of prospective trials before such a strategy could be considered.
But importantly, in their patients who had been continuously monitored by their cardiac implantable electronic devices (CIEDs) prior to experiencing a stroke, the 30-day risk of that stroke more than tripled if their AFib burden on 1 day reached at least 5-6 hours. The risk jumped especially high within the first few days after accumulating that amount of AFib in a day, but then fell off sharply over the next few days.
Based on the study, “Your risk of stroke goes up acutely when you have an episode of AFib, and it decreases rapidly, back to baseline – certainly by 30 days and it looked like in our data by 5 days,” Daniel E. Singer, MD, of Massachusetts General Hospital, Boston, said in an interview.
Increasingly, he noted, “there’s a widespread belief that AFib is a risk marker, not a causal risk factor.” In that scenario, most embolic strokes are caused by thrombi formed as a result of an atrial myopathy, characterized by fibrosis and inflammation, that also happens to trigger AFib.
But said Dr. Singer, who is lead author on the analysis published online Sept. 29 in JAMA Cardiology.
Some studies have “shown that anticoagulants seem to lower stroke risk even in patients without atrial fib, and even from sources not likely to be coming from the atrium,” Mintu P. Turakhia, MD, of Stanford (Calif.) University, Palo Alto, said in an interview. Collectively they point to “atrial fibrillation as a cause of and a noncausal marker for stroke.”
For example, Dr. Turakhia pointed out in an editorial accompanying the current report that stroke in patients with CIEDs “may occur during prolonged periods of sinus rhythm.”
The current study, he said in an interview, doesn’t preclude atrial myopathy as one direct cause of stroke-associated thrombus, because probably both the myopathy and AFib can be culprits. Still, AFib itself it may bear more responsibility for strokes in patients with fewer competing risks for stroke.
In such patients at lower vascular risk, who may have a CHA2DS2-VASc score of only 1 or 2, for example, “AFib can become a more important cause” of ischemic stroke, Dr. Turakhia said. That’s when AFib is more likely to be temporally related to stroke as the likely culprit, the mechanism addressed by Dr. Singer and associates.
“I think we’re all trying to grapple with what the truth is,” Dr. Singer observed. Still, the current study was unusual for primarily looking at the temporal relationship between AFib and stroke, rather than stroke risk. “And once again, as we found in our earlier study, but now a much larger study, it’s a tight relationship.”
Based on the current results, he said, the risk is “high when you have AFib, and it decreases very rapidly after the AFib is over.” And, “it takes multiple hours of AFib to raise stroke risk.” Inclusion in the analysis required accumulation of at least 5.5 hours of AFib on at least 1 day in a month, the cut point at which stroke risk started to climb significantly in an earlier trial.
In the current analysis, however, the 30-day odds ratio for stroke was a nonsignificant 2.75 for an AFib burden of 6-23 hours in a day and jumped to a significant 5.0 for a burden in excess of 23 hours in a day. “That’s a lot of AFib” before the risk actually goes up, and supports AFib as causative, Dr. Singer said. If it were the myopathy itself triggering stroke in these particular patients, the risk would be ongoing and not subject to a threshold of AFib burden.
Implications for noncontinuous OAC
“The hope is that there are people who have very little AFib: They may have several hours, and then they have nothing for 6 months. Do they have to be anticoagulated or not?” Dr. Singer asked.
“If you believe the risk-marker story, you might say they have to be anticoagulated. But if you believe our results, you would certainly think there’s a good chance they don’t have to be anticoagulated,” he said.
“So it is logical to think, if you have the right people and continuous monitoring, that you could have time-delimited anticoagulation.” That is, patients might start right away on a direct OAC once reaching the AFib threshold in a day, Dr. Singer said, “going on and off anticoagulants in parallel with their episodes of AFib.”
The strategy wouldn’t be feasible in patients who often experience AFib, Dr. Singer noted, “but it might work for people who have infrequent paroxysmal AFib.” It certainly would first have to be tested in prospective trials, he said. Such trials would be more practical than ever to carry out given the growing availability of continuous AFib monitoring by wearables.
“We need a trial to make the case whether it’s safe or not,” Dr. Turakhia said of such a rhythm-guided approach to OAC for AFib. The population to start with, he said, would be patients with paroxysmal AFib and low CHA2DS2-VASc scores. “If you think CHA2DS2-VASc as an integrated score of vascular risk, such patients would have a lot fewer reasons to have strokes. And if they do have a stroke, it’s more reasonable to assume that it’s likely caused by atrial fib and not just a marker.”
Importantly, such a strategy could well be safer than continuous OAC for some patients – those at the lowest vascular risk and with the most occasional AFib and lowest AFib burden “who are otherwise doing fine,” Dr. Turakhia said. In such patients on continuous OAC, he proposed, the risks of bleeding and intracranial hemorrhage could potentially exceed the expected degree of protection from ischemic events.
Discordant periods of AFib burden
Dr. Singer and his colleagues linked a national electronic health record database with Medtronic CareLink records covering 10 years to identify 891 patients who experienced an ischemic stroke preceded by at least 120 days of continuous heart-rhythm monitoring.
The patients were then categorized by their pattern of AFib, if any, within each of two prestroke periods: the most recent 30 days, which was the test period, and the preceding 91-120 days, the control period.
The analysis then excluded any patients who reached an AFib-burden threshold of at least 5.5 hours on any day during both the test and control periods, and those who did not attain that threshold in either period.
“The ones who had AFib in both periods mostly had permanent AFib, and ones that didn’t have AFib in either period mostly were in sinus rhythm,” Dr. Singer said. It was “close to 100%” in both cases.
Those exclusions left 66 patients, 7.4% of the total, who reached the AFib-burden threshold on at least 1 day during either the test or control periods, but not both. They included 52 and 14 patients, respectively, with “discordant” periods, that is, at least that burden of AFib in a day during either the test or control period, but not both.
Comparing AFib burden at test versus control periods among patients for whom the two periods were discordant yielded an OR for stroke of 3.71 (95% confidence interval, 2.06-6.70).
Stroke risk levels were not evenly spread throughout the 24-hour periods that met the AFib-burden threshold or the 30 days preceding the patients’ strokes. The OR for stroke was 5.00 (95% CI, 2.62-9.55) during days 1-5 following the day in which the AFib-burden threshold was met. And it was 5.00 (95% CI, 2.08-12.01) over 30 days if the AFib burden exceeded 23 hours on any day of the test period.
The study’s case-crossover design, in which each patient served as their own control, is one of its advantages, Dr. Singer observed. Most patient features, including CHA2DS2-VASc score and comorbidities, did not change appreciably from earliest to the latest 30-day period, which strengthens the comparison of the two because “you don’t have to worry about long-term confounding.”
Dr. Singer was supported by the Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital. He discloses receiving grants from Boehringer Ingelheim and Bristol-Myers Squibb; personal fees from Boehringer Ingelheim, Bristol-Myers Squibb, Fitbit, Johnson & Johnson, Merck, and Pfizer; and royalties from UpToDate.
Dr. Turakhia discloses personal fees from Medtronic, Abbott, Sanofi, Pfizer, Myokardia, Johnson & Johnson, Milestone Pharmaceuticals, InCarda Therapeutics, 100Plus, Forward Pharma, and AliveCor; and grants from Bristol-Myers Squibb, the American Heart Association, Apple, and Bayer.
A version of this article first appeared on Medscape.com.
Assessing headache severity via migraine symptoms can help predict outcomes
according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.
“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.
To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.
After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
Tracking multiple variables
“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.
“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”
He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.
“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”
The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”
The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.
according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.
“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.
To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.
After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
Tracking multiple variables
“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.
“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”
He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.
“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”
The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”
The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.
according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.
“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.
To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.
After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
Tracking multiple variables
“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.
“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”
He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.
“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”
The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”
The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.
FROM CEPHALALGIA
ADHD a new risk factor for Alzheimer’s?
results from a large, multigenerational study show.
“The findings suggest there are common genetic and/or environmental contributions to the association between ADHD and dementia,” study investigator Zheng Chang, PhD, from the department of medical epidemiology and biostatistics at Karolinska Institute, Stockholm, said in a statement.
“There have been few studies previously on the link between ADHD and dementia, all with limited sample size,” Dr. Chang said in an interview.
“This is the first study to look at ADHD and dementia within extended families. It’s a large population-based study including over 2 million individuals and their over 5 million biological relatives,” he noted.
The study was published online Sept. 9, 2021, in the journal Alzheimer’s & Dementia.
Shared familial risk
The researchers identified roughly 2.1 million people born in Sweden between 1980 and 2001. Overall, 3.2% of the cohort had a diagnosis of ADHD.
Using national registries, they linked these individuals to more than 5 million of their biological relatives including parents, grandparents, uncles, and aunts and determined which of these relatives developed dementia over time.
In adjusted analyses, parents of individuals with ADHD had 34% higher risk for any dementia than parents of those without ADHD (hazard ratio, 1.34; 95% CI, 1.11-1.63).
The risk for AD, the most common type of dementia, was 55% higher in parents of individuals with ADHD (HR, 1.55; 95% CI, 1.26-1.89).
Individuals with ADHD were more likely to have parents with early-onset dementia rather than late-onset dementia. However, the absolute risk for dementia was low for the parent cohort: Only 0.17% of the parents were diagnosed with dementia during follow-up.
The association between ADHD and dementia was not as strong for second-degree relatives of individuals with ADHD. For example, grandparents of individuals with ADHD had a 10% increased risk for dementia, compared with grandparents of individuals without ADHD.
The finding of attenuated associations with decreasing genetic relatedness (parents > grandparents and uncles/aunts), points to shared familial risk between ADHD and AD, the researchers said.
There could be “undiscovered genetic variants that contribute to either traits or family-wide environmental risk factors, such as socioeconomic status, that may have an impact on the association,” Dr. Chang said in the news release.
“There are no direct clinical implications from this study, but research like this could lead to further research with goals for improved detection, prevention, and treatment,” he said in an interview.
More questions than answers
Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association that the way different brain diseases are linked “is a question the Alzheimer’s Association is often asked, and it is a part of our funding portfolio to get that question answered.”
This study looking at ADHD and dementia is “intriguing,” Dr. Snyder said, “because, right now, there is limited information available. That said, this is an association study; it shows that two things are somehow connected. Because of how the study was conducted, it does not – and cannot – prove causation,” Dr. Snyder said. “But it is interesting all the same. More research is needed to uncover specifically why and how these two diseases are related. That might eventually give us insight into how to manage risk or even improve treatment.”
The study was supported by grants from the Swedish Council for Health, Working Life and Welfare, the Swedish Research Council, the Swedish Brain Foundation, the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie, the Fredrik & Ingrid Thurings Stiftelse, and the Karolinska Institutet Research Foundation. Dr. Chang and Dr. Snyder disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
results from a large, multigenerational study show.
“The findings suggest there are common genetic and/or environmental contributions to the association between ADHD and dementia,” study investigator Zheng Chang, PhD, from the department of medical epidemiology and biostatistics at Karolinska Institute, Stockholm, said in a statement.
“There have been few studies previously on the link between ADHD and dementia, all with limited sample size,” Dr. Chang said in an interview.
“This is the first study to look at ADHD and dementia within extended families. It’s a large population-based study including over 2 million individuals and their over 5 million biological relatives,” he noted.
The study was published online Sept. 9, 2021, in the journal Alzheimer’s & Dementia.
Shared familial risk
The researchers identified roughly 2.1 million people born in Sweden between 1980 and 2001. Overall, 3.2% of the cohort had a diagnosis of ADHD.
Using national registries, they linked these individuals to more than 5 million of their biological relatives including parents, grandparents, uncles, and aunts and determined which of these relatives developed dementia over time.
In adjusted analyses, parents of individuals with ADHD had 34% higher risk for any dementia than parents of those without ADHD (hazard ratio, 1.34; 95% CI, 1.11-1.63).
The risk for AD, the most common type of dementia, was 55% higher in parents of individuals with ADHD (HR, 1.55; 95% CI, 1.26-1.89).
Individuals with ADHD were more likely to have parents with early-onset dementia rather than late-onset dementia. However, the absolute risk for dementia was low for the parent cohort: Only 0.17% of the parents were diagnosed with dementia during follow-up.
The association between ADHD and dementia was not as strong for second-degree relatives of individuals with ADHD. For example, grandparents of individuals with ADHD had a 10% increased risk for dementia, compared with grandparents of individuals without ADHD.
The finding of attenuated associations with decreasing genetic relatedness (parents > grandparents and uncles/aunts), points to shared familial risk between ADHD and AD, the researchers said.
There could be “undiscovered genetic variants that contribute to either traits or family-wide environmental risk factors, such as socioeconomic status, that may have an impact on the association,” Dr. Chang said in the news release.
“There are no direct clinical implications from this study, but research like this could lead to further research with goals for improved detection, prevention, and treatment,” he said in an interview.
More questions than answers
Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association that the way different brain diseases are linked “is a question the Alzheimer’s Association is often asked, and it is a part of our funding portfolio to get that question answered.”
This study looking at ADHD and dementia is “intriguing,” Dr. Snyder said, “because, right now, there is limited information available. That said, this is an association study; it shows that two things are somehow connected. Because of how the study was conducted, it does not – and cannot – prove causation,” Dr. Snyder said. “But it is interesting all the same. More research is needed to uncover specifically why and how these two diseases are related. That might eventually give us insight into how to manage risk or even improve treatment.”
The study was supported by grants from the Swedish Council for Health, Working Life and Welfare, the Swedish Research Council, the Swedish Brain Foundation, the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie, the Fredrik & Ingrid Thurings Stiftelse, and the Karolinska Institutet Research Foundation. Dr. Chang and Dr. Snyder disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
results from a large, multigenerational study show.
“The findings suggest there are common genetic and/or environmental contributions to the association between ADHD and dementia,” study investigator Zheng Chang, PhD, from the department of medical epidemiology and biostatistics at Karolinska Institute, Stockholm, said in a statement.
“There have been few studies previously on the link between ADHD and dementia, all with limited sample size,” Dr. Chang said in an interview.
“This is the first study to look at ADHD and dementia within extended families. It’s a large population-based study including over 2 million individuals and their over 5 million biological relatives,” he noted.
The study was published online Sept. 9, 2021, in the journal Alzheimer’s & Dementia.
Shared familial risk
The researchers identified roughly 2.1 million people born in Sweden between 1980 and 2001. Overall, 3.2% of the cohort had a diagnosis of ADHD.
Using national registries, they linked these individuals to more than 5 million of their biological relatives including parents, grandparents, uncles, and aunts and determined which of these relatives developed dementia over time.
In adjusted analyses, parents of individuals with ADHD had 34% higher risk for any dementia than parents of those without ADHD (hazard ratio, 1.34; 95% CI, 1.11-1.63).
The risk for AD, the most common type of dementia, was 55% higher in parents of individuals with ADHD (HR, 1.55; 95% CI, 1.26-1.89).
Individuals with ADHD were more likely to have parents with early-onset dementia rather than late-onset dementia. However, the absolute risk for dementia was low for the parent cohort: Only 0.17% of the parents were diagnosed with dementia during follow-up.
The association between ADHD and dementia was not as strong for second-degree relatives of individuals with ADHD. For example, grandparents of individuals with ADHD had a 10% increased risk for dementia, compared with grandparents of individuals without ADHD.
The finding of attenuated associations with decreasing genetic relatedness (parents > grandparents and uncles/aunts), points to shared familial risk between ADHD and AD, the researchers said.
There could be “undiscovered genetic variants that contribute to either traits or family-wide environmental risk factors, such as socioeconomic status, that may have an impact on the association,” Dr. Chang said in the news release.
“There are no direct clinical implications from this study, but research like this could lead to further research with goals for improved detection, prevention, and treatment,” he said in an interview.
More questions than answers
Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association that the way different brain diseases are linked “is a question the Alzheimer’s Association is often asked, and it is a part of our funding portfolio to get that question answered.”
This study looking at ADHD and dementia is “intriguing,” Dr. Snyder said, “because, right now, there is limited information available. That said, this is an association study; it shows that two things are somehow connected. Because of how the study was conducted, it does not – and cannot – prove causation,” Dr. Snyder said. “But it is interesting all the same. More research is needed to uncover specifically why and how these two diseases are related. That might eventually give us insight into how to manage risk or even improve treatment.”
The study was supported by grants from the Swedish Council for Health, Working Life and Welfare, the Swedish Research Council, the Swedish Brain Foundation, the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie, the Fredrik & Ingrid Thurings Stiftelse, and the Karolinska Institutet Research Foundation. Dr. Chang and Dr. Snyder disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Lipid levels tied to ALS risk
, new research shows.
The study also linked a higher ratio of total cholesterol to HDL with an increased risk for ALS. These findings, investigators noted, point to potential future biomarkers in screening for ALS and perhaps an approach to reduce risk or delay onset of ALS in the longer term.
“They may help build a biochemical picture of what’s going on and who might be at risk of developing ALS in the near future, particularly in people with a genetic predisposition to ALS,” study investigator Alexander G. Thompson, DPhil, Medical Research Council clinician scientist, Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom, said in an interview.
He emphasized that although the current observational study cannot show cause and effect, such a relationship may exist.
The study was published online September 13 in the Journal of Neurology, Neurosurgery and Psychiatry.
Registry data
ALS is a disorder of progressive degeneration of upper and lower motor neurons. Genetic variants account for fewer than 15% of cases. The factors that are associated with the greatest risk are unclear.
To investigate, the researchers used data from the UK Biobank, a prospective cohort study of persons aged 39-72 years. Participants underwent an initial assessment between March 2006 and October 2010 and were followed for a median of 11.9 years.
In addition to providing demographic and health information, participants provided blood samples for biochemical analysis. This included measurements of total cholesterol, HDL, low-density lipoprotein (LDL) cholesterol, triglycerides, apoA1, apolipoprotein B (apoB), A1c, and creatinine.
Researchers used diagnostic codes in inpatient health records and death certificate information to verify ALS diagnoses.
The analysis included data from 502,409 participants. The mean age of the participants was 58 years, and 54.4% were women. During follow-up, 343 participants were diagnosed with ALS, yielding a crude incidence of 5.85 per 100,000 per year (95% confidence interval, 5.25-6.51).
After controlling for sex and age, results showed that higher HDL (hazard ratio, 0.84; 95% CI, 0.73-0.96; P = .010) and higher apoA1 (HR, 0.83; 95% CI, 0.72-0.94, P = .005) were associated with a reduced risk for subsequent ALS.
A higher ratio of total cholesterol to HDL was associated with increased ALS risk.
A rise in neurofilaments and other markers of neuronal loss typically occur within about a year of ALS symptom onset. To ensure that they were capturing participants whose blood samples were taken before the onset of neurodegeneration, the researchers performed a secondary analysis that excluded ALS diagnoses within 5 years of the baseline study visit.
Results of the analysis were largely consistent with models incorporating all participants with regard to magnitude and direction of associations. In addition, the findings persisted in models that controlled for statin use, smoking, and vascular disease.
Mechanism unclear
To more closely examine lipid status prior to ALS diagnosis, the researchers performed a nested case-control analysis that involved matching each participant who developed ALS with 20 participants of similar age, sex, and time of enrollment who did not develop the disease.
Linear models showed that levels of LDL and apoB, which are closely correlated, decrease over time in those who developed ALS. This was not the case for HDL and apoA1. “This suggests LDL levels are going down, and we think it’s happening quite some time before symptoms start, even before neurodegeneration starts,” said Dr. Thompson.
How blood lipid levels correlate with ALS risk is unclear. Dr. Thompson noted that LDL is an oxidative stressor and can provoke inflammation, whereas HDL is an antioxidant that is involved in healing. However, given that LDL and HDL don’t cross into the brain in great amounts, “the lipid changes may be a reflection of something else going on that contributes to the risk of ALS,” he said.
More evidence of a causal relationship is needed before any clinical implications can be drawn, including the potential manipulation of lipid levels to prevent ALS, said Dr. Thompson. In addition, even were such a relationship to be established, altering lipid levels in a healthy individual who has no family history of ALS would be unlikely to alter risk.
Dr. Thompson added that among those with a genetic predisposition, lipid changes “may be a marker or clue that something’s going wrong in the nervous system and that ALS might be about to start. That would be the ideal time to treat people at risk of ALS with gene therapy.”
Metabolism gone awry
Commenting on the findings, Stephen Goutman, MD, director, Pranger ALS Clinic, associate professor of neurology, Neuromuscular Program, University of Michigan, Ann Arbor, called the study “very interesting.” Of particular note was a trend of decreasing LDL and apoB levels prior to an ALS diagnosis, said Dr. Goutman.
The results are in agreement with several studies that show an alteration in metabolism in individuals with ALS, he said. “These altered metabolic pathways may provide some signal that something has gone awry,” he commented.
He agreed that an “ultimate goal” is to identify factors or biomarkers that can be used to predict whether individuals will develop ALS and to enable intervention to decrease the risk.
This new research highlights the value of population-based registries and large prospective cohorts, said Dr. Goutman. “These help to better define the genetic, environmental, and metabolic factors that increase and predict ALS risk,” he said.
But more work is needed, said Dr. Goutman. He noted that in the study, only 192 participants were diagnosed with ALS more than 5 years after enrollment. “This means additional large cohort studies are needed, especially those that reflect the diversity of the population, for us to solve the mystery of ALS and to prevent it,” he said.
Dr. Thompson and Dr. Goutman have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
The study also linked a higher ratio of total cholesterol to HDL with an increased risk for ALS. These findings, investigators noted, point to potential future biomarkers in screening for ALS and perhaps an approach to reduce risk or delay onset of ALS in the longer term.
“They may help build a biochemical picture of what’s going on and who might be at risk of developing ALS in the near future, particularly in people with a genetic predisposition to ALS,” study investigator Alexander G. Thompson, DPhil, Medical Research Council clinician scientist, Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom, said in an interview.
He emphasized that although the current observational study cannot show cause and effect, such a relationship may exist.
The study was published online September 13 in the Journal of Neurology, Neurosurgery and Psychiatry.
Registry data
ALS is a disorder of progressive degeneration of upper and lower motor neurons. Genetic variants account for fewer than 15% of cases. The factors that are associated with the greatest risk are unclear.
To investigate, the researchers used data from the UK Biobank, a prospective cohort study of persons aged 39-72 years. Participants underwent an initial assessment between March 2006 and October 2010 and were followed for a median of 11.9 years.
In addition to providing demographic and health information, participants provided blood samples for biochemical analysis. This included measurements of total cholesterol, HDL, low-density lipoprotein (LDL) cholesterol, triglycerides, apoA1, apolipoprotein B (apoB), A1c, and creatinine.
Researchers used diagnostic codes in inpatient health records and death certificate information to verify ALS diagnoses.
The analysis included data from 502,409 participants. The mean age of the participants was 58 years, and 54.4% were women. During follow-up, 343 participants were diagnosed with ALS, yielding a crude incidence of 5.85 per 100,000 per year (95% confidence interval, 5.25-6.51).
After controlling for sex and age, results showed that higher HDL (hazard ratio, 0.84; 95% CI, 0.73-0.96; P = .010) and higher apoA1 (HR, 0.83; 95% CI, 0.72-0.94, P = .005) were associated with a reduced risk for subsequent ALS.
A higher ratio of total cholesterol to HDL was associated with increased ALS risk.
A rise in neurofilaments and other markers of neuronal loss typically occur within about a year of ALS symptom onset. To ensure that they were capturing participants whose blood samples were taken before the onset of neurodegeneration, the researchers performed a secondary analysis that excluded ALS diagnoses within 5 years of the baseline study visit.
Results of the analysis were largely consistent with models incorporating all participants with regard to magnitude and direction of associations. In addition, the findings persisted in models that controlled for statin use, smoking, and vascular disease.
Mechanism unclear
To more closely examine lipid status prior to ALS diagnosis, the researchers performed a nested case-control analysis that involved matching each participant who developed ALS with 20 participants of similar age, sex, and time of enrollment who did not develop the disease.
Linear models showed that levels of LDL and apoB, which are closely correlated, decrease over time in those who developed ALS. This was not the case for HDL and apoA1. “This suggests LDL levels are going down, and we think it’s happening quite some time before symptoms start, even before neurodegeneration starts,” said Dr. Thompson.
How blood lipid levels correlate with ALS risk is unclear. Dr. Thompson noted that LDL is an oxidative stressor and can provoke inflammation, whereas HDL is an antioxidant that is involved in healing. However, given that LDL and HDL don’t cross into the brain in great amounts, “the lipid changes may be a reflection of something else going on that contributes to the risk of ALS,” he said.
More evidence of a causal relationship is needed before any clinical implications can be drawn, including the potential manipulation of lipid levels to prevent ALS, said Dr. Thompson. In addition, even were such a relationship to be established, altering lipid levels in a healthy individual who has no family history of ALS would be unlikely to alter risk.
Dr. Thompson added that among those with a genetic predisposition, lipid changes “may be a marker or clue that something’s going wrong in the nervous system and that ALS might be about to start. That would be the ideal time to treat people at risk of ALS with gene therapy.”
Metabolism gone awry
Commenting on the findings, Stephen Goutman, MD, director, Pranger ALS Clinic, associate professor of neurology, Neuromuscular Program, University of Michigan, Ann Arbor, called the study “very interesting.” Of particular note was a trend of decreasing LDL and apoB levels prior to an ALS diagnosis, said Dr. Goutman.
The results are in agreement with several studies that show an alteration in metabolism in individuals with ALS, he said. “These altered metabolic pathways may provide some signal that something has gone awry,” he commented.
He agreed that an “ultimate goal” is to identify factors or biomarkers that can be used to predict whether individuals will develop ALS and to enable intervention to decrease the risk.
This new research highlights the value of population-based registries and large prospective cohorts, said Dr. Goutman. “These help to better define the genetic, environmental, and metabolic factors that increase and predict ALS risk,” he said.
But more work is needed, said Dr. Goutman. He noted that in the study, only 192 participants were diagnosed with ALS more than 5 years after enrollment. “This means additional large cohort studies are needed, especially those that reflect the diversity of the population, for us to solve the mystery of ALS and to prevent it,” he said.
Dr. Thompson and Dr. Goutman have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
The study also linked a higher ratio of total cholesterol to HDL with an increased risk for ALS. These findings, investigators noted, point to potential future biomarkers in screening for ALS and perhaps an approach to reduce risk or delay onset of ALS in the longer term.
“They may help build a biochemical picture of what’s going on and who might be at risk of developing ALS in the near future, particularly in people with a genetic predisposition to ALS,” study investigator Alexander G. Thompson, DPhil, Medical Research Council clinician scientist, Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom, said in an interview.
He emphasized that although the current observational study cannot show cause and effect, such a relationship may exist.
The study was published online September 13 in the Journal of Neurology, Neurosurgery and Psychiatry.
Registry data
ALS is a disorder of progressive degeneration of upper and lower motor neurons. Genetic variants account for fewer than 15% of cases. The factors that are associated with the greatest risk are unclear.
To investigate, the researchers used data from the UK Biobank, a prospective cohort study of persons aged 39-72 years. Participants underwent an initial assessment between March 2006 and October 2010 and were followed for a median of 11.9 years.
In addition to providing demographic and health information, participants provided blood samples for biochemical analysis. This included measurements of total cholesterol, HDL, low-density lipoprotein (LDL) cholesterol, triglycerides, apoA1, apolipoprotein B (apoB), A1c, and creatinine.
Researchers used diagnostic codes in inpatient health records and death certificate information to verify ALS diagnoses.
The analysis included data from 502,409 participants. The mean age of the participants was 58 years, and 54.4% were women. During follow-up, 343 participants were diagnosed with ALS, yielding a crude incidence of 5.85 per 100,000 per year (95% confidence interval, 5.25-6.51).
After controlling for sex and age, results showed that higher HDL (hazard ratio, 0.84; 95% CI, 0.73-0.96; P = .010) and higher apoA1 (HR, 0.83; 95% CI, 0.72-0.94, P = .005) were associated with a reduced risk for subsequent ALS.
A higher ratio of total cholesterol to HDL was associated with increased ALS risk.
A rise in neurofilaments and other markers of neuronal loss typically occur within about a year of ALS symptom onset. To ensure that they were capturing participants whose blood samples were taken before the onset of neurodegeneration, the researchers performed a secondary analysis that excluded ALS diagnoses within 5 years of the baseline study visit.
Results of the analysis were largely consistent with models incorporating all participants with regard to magnitude and direction of associations. In addition, the findings persisted in models that controlled for statin use, smoking, and vascular disease.
Mechanism unclear
To more closely examine lipid status prior to ALS diagnosis, the researchers performed a nested case-control analysis that involved matching each participant who developed ALS with 20 participants of similar age, sex, and time of enrollment who did not develop the disease.
Linear models showed that levels of LDL and apoB, which are closely correlated, decrease over time in those who developed ALS. This was not the case for HDL and apoA1. “This suggests LDL levels are going down, and we think it’s happening quite some time before symptoms start, even before neurodegeneration starts,” said Dr. Thompson.
How blood lipid levels correlate with ALS risk is unclear. Dr. Thompson noted that LDL is an oxidative stressor and can provoke inflammation, whereas HDL is an antioxidant that is involved in healing. However, given that LDL and HDL don’t cross into the brain in great amounts, “the lipid changes may be a reflection of something else going on that contributes to the risk of ALS,” he said.
More evidence of a causal relationship is needed before any clinical implications can be drawn, including the potential manipulation of lipid levels to prevent ALS, said Dr. Thompson. In addition, even were such a relationship to be established, altering lipid levels in a healthy individual who has no family history of ALS would be unlikely to alter risk.
Dr. Thompson added that among those with a genetic predisposition, lipid changes “may be a marker or clue that something’s going wrong in the nervous system and that ALS might be about to start. That would be the ideal time to treat people at risk of ALS with gene therapy.”
Metabolism gone awry
Commenting on the findings, Stephen Goutman, MD, director, Pranger ALS Clinic, associate professor of neurology, Neuromuscular Program, University of Michigan, Ann Arbor, called the study “very interesting.” Of particular note was a trend of decreasing LDL and apoB levels prior to an ALS diagnosis, said Dr. Goutman.
The results are in agreement with several studies that show an alteration in metabolism in individuals with ALS, he said. “These altered metabolic pathways may provide some signal that something has gone awry,” he commented.
He agreed that an “ultimate goal” is to identify factors or biomarkers that can be used to predict whether individuals will develop ALS and to enable intervention to decrease the risk.
This new research highlights the value of population-based registries and large prospective cohorts, said Dr. Goutman. “These help to better define the genetic, environmental, and metabolic factors that increase and predict ALS risk,” he said.
But more work is needed, said Dr. Goutman. He noted that in the study, only 192 participants were diagnosed with ALS more than 5 years after enrollment. “This means additional large cohort studies are needed, especially those that reflect the diversity of the population, for us to solve the mystery of ALS and to prevent it,” he said.
Dr. Thompson and Dr. Goutman have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From Journal of Neurology, Neurosurgery, and Psychiatry
Data supporting cannabis for childhood epilepsy remain scarce
, according to two leading experts.
In a recent invited review article, Martin Kirkpatrick, MD, of the University of Dundee (Scotland), and Finbar O’Callaghan, MD, PhD, of University College London suggested that childhood epilepsy may be easy terrain for commercial interests to break ground, and from there, build their presence.
“Children with epilepsy are at risk of being used as the ‘Trojan horse’ for the cannabis industry,” Dr. Kirkpatrick and Dr. O’Callaghan wrote in Developmental Medicine & Child Neurology.
They noted that some of the first publicized success stories involving cannabis oil for epilepsy coincided with the rise of the medicinal and recreational cannabis markets, which will constitute an estimated 55-billion-dollar industry by 2027.
“Pediatric neurologists, imbued with the need to practice evidence-based medicine and wary of prescribing unlicensed medicines that had inadequate safety data, suddenly found themselves at odds with an array of vested interests and, most unfortunately, with the families of patients who were keen to try anything that would alleviate the effects of their child’s seizures,” the investigators wrote.
According to the review, fundamental questions about cannabis remain unanswered, including concerns about safety with long-term use, and the medicinal value of various plant components, such as myrcene, a terpene that gives cannabis its characteristic smell.
“A widely discussed issue is whether the terpenes add any therapeutic benefit, contributing to the so-called entourage effect of ‘whole-plant’ medicines,” the investigators wrote. “The concept is that all the constituents of the plant together create ‘the sum of all the parts that leads to the magic or power of cannabis.’ Although commonly referred to, there is little or no robust evidence to support the entourage effect as a credible clinical concept.”
Clinical evidence for treatment of pediatric epilepsy is also lacking, according to Dr. Kirkpatrick and Dr. O’Callaghan.
“Unfortunately, apart from the studies of pure cannabidiol (CBD) in Lennox–Gastaut and Dravet syndromes and tuberous sclerosis complex, level I evidence in the field of CBMPs and refractory epilepsy is lacking,” they wrote.
While other experts have pointed out that lower-level evidence – such as patient-reported outcomes and observational data – have previously been sufficient for drug licensing, Dr. Kirkpatrick and Dr. O’Callaghan noted that such exceptions “almost always” involve conditions without any effective treatments, or drugs that are undeniably effective.
“This is not the scenario with CBMPs,” they wrote, referring to current clinical data as “low-level” evidence “suggesting … possible efficacy.”
They highlighted concerns about placebo effect with open-label epilepsy studies, citing a randomized controlled trial for Dravet syndrome, in which 27% of patients given placebo had a 50% reduction in seizure frequency.
“We need carefully designed, good-quality CBMP studies that produce results on which we can rely,” Dr. Kirkpatrick and Dr. O’Callaghan concluded. “We can then work with families to choose the best treatments for children and young people with epilepsy. We owe this to them.”
A therapy of last resort
Jerzy P. Szaflarski, MD, PhD, of the University of Alabama at Birmingham, agreed that data are lacking for the use of CBMPs with patients who have epilepsy and other neurologic conditions; however, he also suggested that Dr. Kirkpatrick and Dr. O’Callaghan did not provide adequate real-world clinical context.
“Medical cannabis is not used as a first-, second-, or third-line therapy,” Dr. Szaflarski said. “It’s mostly used as a last resort in the sense that patients have already failed multiple other therapies.” In that respect, patients and parents are desperate to try anything that might work. “We have medical cannabis, and our patients want to try it, and at the point when multiple therapies have failed, it’s a reasonable option.”
While Dr. Szaflarski agreed that more high-quality clinical trials are needed, he also noted the practical challenges involved in such trials, largely because of variations in cannabis plants.
“The content of the cannabis plant changes depending on the day that it’s collected and the exposure to sun and how much water it has and what’s in the soil and many other things,” Dr. Szaflarski said. “It’s hard to get a very good, standardized product, and that’s why there needs to be a good-quality product delivered by the industry, which I have not seen thus far.”
For this reason, Dr. Szaflarski steers parents and patients away from over-the-counter CBMPs and toward Epidiolex, the only FDA-approved form of CBD.
“There is evidence that Epidiolex works,” he said. “I don’t know whether the products that are sold in a local cannabis store have the same high purity as Epidiolex. I tell [parents] that we should try Epidiolex first because it’s the one that is approved. But if it doesn’t work, we can go in that [other] direction.”
For those going the commercial route, Dr. Szaflarski advised close attention to product ingredients, to ensure that CBMPs are “devoid of any impurities, pesticides, fungicides, and other products that could be potentially dangerous.”
Parents considering CBMPs for their children also need to weigh concerns about long-term neurological safety, he added, noting that, on one hand, commercial products lack data, while on the other, epilepsy itself may cause harm.
“They need to consider the potential effects [of CBMPs] on their child’s brain and development versus … the effects of seizures on the brain,” Dr. Szaflarski said.
Dr. Kirkpatrick and Dr. O’Callaghan disclosed an application for a National Institute for Health Research–funded randomized controlled trial on CBMPs and joint authorship of British Paediatric Neurology Association Guidance on the use of CBMPs in children and young people with epilepsy. Dr. Szaflarski disclosed a relationship with Greenwich Biosciences and several other cannabis companies.
, according to two leading experts.
In a recent invited review article, Martin Kirkpatrick, MD, of the University of Dundee (Scotland), and Finbar O’Callaghan, MD, PhD, of University College London suggested that childhood epilepsy may be easy terrain for commercial interests to break ground, and from there, build their presence.
“Children with epilepsy are at risk of being used as the ‘Trojan horse’ for the cannabis industry,” Dr. Kirkpatrick and Dr. O’Callaghan wrote in Developmental Medicine & Child Neurology.
They noted that some of the first publicized success stories involving cannabis oil for epilepsy coincided with the rise of the medicinal and recreational cannabis markets, which will constitute an estimated 55-billion-dollar industry by 2027.
“Pediatric neurologists, imbued with the need to practice evidence-based medicine and wary of prescribing unlicensed medicines that had inadequate safety data, suddenly found themselves at odds with an array of vested interests and, most unfortunately, with the families of patients who were keen to try anything that would alleviate the effects of their child’s seizures,” the investigators wrote.
According to the review, fundamental questions about cannabis remain unanswered, including concerns about safety with long-term use, and the medicinal value of various plant components, such as myrcene, a terpene that gives cannabis its characteristic smell.
“A widely discussed issue is whether the terpenes add any therapeutic benefit, contributing to the so-called entourage effect of ‘whole-plant’ medicines,” the investigators wrote. “The concept is that all the constituents of the plant together create ‘the sum of all the parts that leads to the magic or power of cannabis.’ Although commonly referred to, there is little or no robust evidence to support the entourage effect as a credible clinical concept.”
Clinical evidence for treatment of pediatric epilepsy is also lacking, according to Dr. Kirkpatrick and Dr. O’Callaghan.
“Unfortunately, apart from the studies of pure cannabidiol (CBD) in Lennox–Gastaut and Dravet syndromes and tuberous sclerosis complex, level I evidence in the field of CBMPs and refractory epilepsy is lacking,” they wrote.
While other experts have pointed out that lower-level evidence – such as patient-reported outcomes and observational data – have previously been sufficient for drug licensing, Dr. Kirkpatrick and Dr. O’Callaghan noted that such exceptions “almost always” involve conditions without any effective treatments, or drugs that are undeniably effective.
“This is not the scenario with CBMPs,” they wrote, referring to current clinical data as “low-level” evidence “suggesting … possible efficacy.”
They highlighted concerns about placebo effect with open-label epilepsy studies, citing a randomized controlled trial for Dravet syndrome, in which 27% of patients given placebo had a 50% reduction in seizure frequency.
“We need carefully designed, good-quality CBMP studies that produce results on which we can rely,” Dr. Kirkpatrick and Dr. O’Callaghan concluded. “We can then work with families to choose the best treatments for children and young people with epilepsy. We owe this to them.”
A therapy of last resort
Jerzy P. Szaflarski, MD, PhD, of the University of Alabama at Birmingham, agreed that data are lacking for the use of CBMPs with patients who have epilepsy and other neurologic conditions; however, he also suggested that Dr. Kirkpatrick and Dr. O’Callaghan did not provide adequate real-world clinical context.
“Medical cannabis is not used as a first-, second-, or third-line therapy,” Dr. Szaflarski said. “It’s mostly used as a last resort in the sense that patients have already failed multiple other therapies.” In that respect, patients and parents are desperate to try anything that might work. “We have medical cannabis, and our patients want to try it, and at the point when multiple therapies have failed, it’s a reasonable option.”
While Dr. Szaflarski agreed that more high-quality clinical trials are needed, he also noted the practical challenges involved in such trials, largely because of variations in cannabis plants.
“The content of the cannabis plant changes depending on the day that it’s collected and the exposure to sun and how much water it has and what’s in the soil and many other things,” Dr. Szaflarski said. “It’s hard to get a very good, standardized product, and that’s why there needs to be a good-quality product delivered by the industry, which I have not seen thus far.”
For this reason, Dr. Szaflarski steers parents and patients away from over-the-counter CBMPs and toward Epidiolex, the only FDA-approved form of CBD.
“There is evidence that Epidiolex works,” he said. “I don’t know whether the products that are sold in a local cannabis store have the same high purity as Epidiolex. I tell [parents] that we should try Epidiolex first because it’s the one that is approved. But if it doesn’t work, we can go in that [other] direction.”
For those going the commercial route, Dr. Szaflarski advised close attention to product ingredients, to ensure that CBMPs are “devoid of any impurities, pesticides, fungicides, and other products that could be potentially dangerous.”
Parents considering CBMPs for their children also need to weigh concerns about long-term neurological safety, he added, noting that, on one hand, commercial products lack data, while on the other, epilepsy itself may cause harm.
“They need to consider the potential effects [of CBMPs] on their child’s brain and development versus … the effects of seizures on the brain,” Dr. Szaflarski said.
Dr. Kirkpatrick and Dr. O’Callaghan disclosed an application for a National Institute for Health Research–funded randomized controlled trial on CBMPs and joint authorship of British Paediatric Neurology Association Guidance on the use of CBMPs in children and young people with epilepsy. Dr. Szaflarski disclosed a relationship with Greenwich Biosciences and several other cannabis companies.
, according to two leading experts.
In a recent invited review article, Martin Kirkpatrick, MD, of the University of Dundee (Scotland), and Finbar O’Callaghan, MD, PhD, of University College London suggested that childhood epilepsy may be easy terrain for commercial interests to break ground, and from there, build their presence.
“Children with epilepsy are at risk of being used as the ‘Trojan horse’ for the cannabis industry,” Dr. Kirkpatrick and Dr. O’Callaghan wrote in Developmental Medicine & Child Neurology.
They noted that some of the first publicized success stories involving cannabis oil for epilepsy coincided with the rise of the medicinal and recreational cannabis markets, which will constitute an estimated 55-billion-dollar industry by 2027.
“Pediatric neurologists, imbued with the need to practice evidence-based medicine and wary of prescribing unlicensed medicines that had inadequate safety data, suddenly found themselves at odds with an array of vested interests and, most unfortunately, with the families of patients who were keen to try anything that would alleviate the effects of their child’s seizures,” the investigators wrote.
According to the review, fundamental questions about cannabis remain unanswered, including concerns about safety with long-term use, and the medicinal value of various plant components, such as myrcene, a terpene that gives cannabis its characteristic smell.
“A widely discussed issue is whether the terpenes add any therapeutic benefit, contributing to the so-called entourage effect of ‘whole-plant’ medicines,” the investigators wrote. “The concept is that all the constituents of the plant together create ‘the sum of all the parts that leads to the magic or power of cannabis.’ Although commonly referred to, there is little or no robust evidence to support the entourage effect as a credible clinical concept.”
Clinical evidence for treatment of pediatric epilepsy is also lacking, according to Dr. Kirkpatrick and Dr. O’Callaghan.
“Unfortunately, apart from the studies of pure cannabidiol (CBD) in Lennox–Gastaut and Dravet syndromes and tuberous sclerosis complex, level I evidence in the field of CBMPs and refractory epilepsy is lacking,” they wrote.
While other experts have pointed out that lower-level evidence – such as patient-reported outcomes and observational data – have previously been sufficient for drug licensing, Dr. Kirkpatrick and Dr. O’Callaghan noted that such exceptions “almost always” involve conditions without any effective treatments, or drugs that are undeniably effective.
“This is not the scenario with CBMPs,” they wrote, referring to current clinical data as “low-level” evidence “suggesting … possible efficacy.”
They highlighted concerns about placebo effect with open-label epilepsy studies, citing a randomized controlled trial for Dravet syndrome, in which 27% of patients given placebo had a 50% reduction in seizure frequency.
“We need carefully designed, good-quality CBMP studies that produce results on which we can rely,” Dr. Kirkpatrick and Dr. O’Callaghan concluded. “We can then work with families to choose the best treatments for children and young people with epilepsy. We owe this to them.”
A therapy of last resort
Jerzy P. Szaflarski, MD, PhD, of the University of Alabama at Birmingham, agreed that data are lacking for the use of CBMPs with patients who have epilepsy and other neurologic conditions; however, he also suggested that Dr. Kirkpatrick and Dr. O’Callaghan did not provide adequate real-world clinical context.
“Medical cannabis is not used as a first-, second-, or third-line therapy,” Dr. Szaflarski said. “It’s mostly used as a last resort in the sense that patients have already failed multiple other therapies.” In that respect, patients and parents are desperate to try anything that might work. “We have medical cannabis, and our patients want to try it, and at the point when multiple therapies have failed, it’s a reasonable option.”
While Dr. Szaflarski agreed that more high-quality clinical trials are needed, he also noted the practical challenges involved in such trials, largely because of variations in cannabis plants.
“The content of the cannabis plant changes depending on the day that it’s collected and the exposure to sun and how much water it has and what’s in the soil and many other things,” Dr. Szaflarski said. “It’s hard to get a very good, standardized product, and that’s why there needs to be a good-quality product delivered by the industry, which I have not seen thus far.”
For this reason, Dr. Szaflarski steers parents and patients away from over-the-counter CBMPs and toward Epidiolex, the only FDA-approved form of CBD.
“There is evidence that Epidiolex works,” he said. “I don’t know whether the products that are sold in a local cannabis store have the same high purity as Epidiolex. I tell [parents] that we should try Epidiolex first because it’s the one that is approved. But if it doesn’t work, we can go in that [other] direction.”
For those going the commercial route, Dr. Szaflarski advised close attention to product ingredients, to ensure that CBMPs are “devoid of any impurities, pesticides, fungicides, and other products that could be potentially dangerous.”
Parents considering CBMPs for their children also need to weigh concerns about long-term neurological safety, he added, noting that, on one hand, commercial products lack data, while on the other, epilepsy itself may cause harm.
“They need to consider the potential effects [of CBMPs] on their child’s brain and development versus … the effects of seizures on the brain,” Dr. Szaflarski said.
Dr. Kirkpatrick and Dr. O’Callaghan disclosed an application for a National Institute for Health Research–funded randomized controlled trial on CBMPs and joint authorship of British Paediatric Neurology Association Guidance on the use of CBMPs in children and young people with epilepsy. Dr. Szaflarski disclosed a relationship with Greenwich Biosciences and several other cannabis companies.
FROM DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY