Neurology

Certain medications that are used to treat benign prostatic hyperplasia (BPH) are associated with a reduced risk for dementia with Lewy bodies (DLB), the second most common neurodegenerative type of dementia after Alzheimer’s disease.

Investigators found older men taking alpha-1 blockers terazosin, doxazosin, or alfuzosin (Tz/Dz/Az) were 40% less likely to develop DLB than those taking tamsulosin and 37% less likely than men taking the 5-alpha reductase inhibitors (5ARI) finasteride and dutasteride.

“These results are exciting because right now there are no drugs to prevent or treat dementia with Lewy bodies,” study investigator Jacob E. Simmering, PhD, of the University of Iowa in Iowa City, said in a press release. “If we can determine that an existing drug can offer protection against this debilitating disease, that has the potential to greatly reduce its effects.”

The findings were published online in Neurology.
 

Increasing ATP Neuroprotective?

In recent years, investigators have speculated that improving metabolic activity in the brain may reduce the risk for Parkinson’s disease (PD). 

In previous studies, the use of Tz/Dz/Az resulted in the activation of phosphoglycerate kinase-1 (PKG1), which increases the availability of adenosine triphosphate (ATP).

There have been case reports of PD being linked to mutations affecting PGK1. Researchers speculate that increased ATP availability in neurons resulting from the activation of PKG1 allows cells to better adapt to aging and synuclein aggregation.

To investigate whether glycolysis-enhancing drugs might be neuroprotective in those with DLB, investigators conducted a retrospective cohort study using a commercial health insurance claims database and a Medicare supplemental health claims database to follow a sample of men aged > 40 years taking Tz, Dz, or Az (n = 126,313), tamsulosin (n = 437,035), or a 5ARI (n = 80,158) for BPH.

Tamsulosin and 5ARI medications do not activate PKG1, so investigators used them as comparators to Tz/Dz/Az. Participants were followed from the medication initiation date until the end of enrollment in the claims databases.

After following claimants for an average of 3 years, 195 participants developed DLB who were taking Tz, Dz, or Az, a rate of 5.21 cases per 10,000 people per year.

During the follow-up period, 1286 participants taking tamsulosin developed DLB, a rate of 10.8 per 10,000 people per year, and among those taking 5ARIs, 193 cases of DLB were reported, a rate of 7.8 per 10,000 people per year.

After matching the groups by age and other health conditions that may explain differences in rates of DLB, men taking Tz/Dz/Az had a 60% lower risk than those taking tamsulosin (P < .001) and a 37% lower risk for developing DLB than those taking the 5ARI medications (P = .012).

“This emerging evidence of a protective association across a spectrum of diseases suggests a broad neuroprotective effect for Tz/Dz/Az, consistent with our hypothesized mechanism that activation of PGK1 increases brain ATP and mitigates neurodegeneration,” the authors wrote.

Study limitations include excluding women from the study, so the findings cannot be generalized to women. Claims analyses were limited to administrative data that could have been incorrect, and the analyses did not include medication dosages.

No study funding or author disclosures were reported.

A version of this article first appeared on Medscape.com.

Certain medications that are used to treat benign prostatic hyperplasia (BPH) are associated with a reduced risk for dementia with Lewy bodies (DLB), the second most common neurodegenerative type of dementia after Alzheimer’s disease.

Investigators found older men taking alpha-1 blockers terazosin, doxazosin, or alfuzosin (Tz/Dz/Az) were 40% less likely to develop DLB than those taking tamsulosin and 37% less likely than men taking the 5-alpha reductase inhibitors (5ARI) finasteride and dutasteride.

“These results are exciting because right now there are no drugs to prevent or treat dementia with Lewy bodies,” study investigator Jacob E. Simmering, PhD, of the University of Iowa in Iowa City, said in a press release. “If we can determine that an existing drug can offer protection against this debilitating disease, that has the potential to greatly reduce its effects.”

The findings were published online in Neurology.
 

Increasing ATP Neuroprotective?

In recent years, investigators have speculated that improving metabolic activity in the brain may reduce the risk for Parkinson’s disease (PD). 

In previous studies, the use of Tz/Dz/Az resulted in the activation of phosphoglycerate kinase-1 (PKG1), which increases the availability of adenosine triphosphate (ATP).

There have been case reports of PD being linked to mutations affecting PGK1. Researchers speculate that increased ATP availability in neurons resulting from the activation of PKG1 allows cells to better adapt to aging and synuclein aggregation.

To investigate whether glycolysis-enhancing drugs might be neuroprotective in those with DLB, investigators conducted a retrospective cohort study using a commercial health insurance claims database and a Medicare supplemental health claims database to follow a sample of men aged > 40 years taking Tz, Dz, or Az (n = 126,313), tamsulosin (n = 437,035), or a 5ARI (n = 80,158) for BPH.

Tamsulosin and 5ARI medications do not activate PKG1, so investigators used them as comparators to Tz/Dz/Az. Participants were followed from the medication initiation date until the end of enrollment in the claims databases.

After following claimants for an average of 3 years, 195 participants developed DLB who were taking Tz, Dz, or Az, a rate of 5.21 cases per 10,000 people per year.

During the follow-up period, 1286 participants taking tamsulosin developed DLB, a rate of 10.8 per 10,000 people per year, and among those taking 5ARIs, 193 cases of DLB were reported, a rate of 7.8 per 10,000 people per year.

After matching the groups by age and other health conditions that may explain differences in rates of DLB, men taking Tz/Dz/Az had a 60% lower risk than those taking tamsulosin (P < .001) and a 37% lower risk for developing DLB than those taking the 5ARI medications (P = .012).

“This emerging evidence of a protective association across a spectrum of diseases suggests a broad neuroprotective effect for Tz/Dz/Az, consistent with our hypothesized mechanism that activation of PGK1 increases brain ATP and mitigates neurodegeneration,” the authors wrote.

Study limitations include excluding women from the study, so the findings cannot be generalized to women. Claims analyses were limited to administrative data that could have been incorrect, and the analyses did not include medication dosages.

No study funding or author disclosures were reported.

A version of this article first appeared on Medscape.com.

Certain medications that are used to treat benign prostatic hyperplasia (BPH) are associated with a reduced risk for dementia with Lewy bodies (DLB), the second most common neurodegenerative type of dementia after Alzheimer’s disease.

Investigators found older men taking alpha-1 blockers terazosin, doxazosin, or alfuzosin (Tz/Dz/Az) were 40% less likely to develop DLB than those taking tamsulosin and 37% less likely than men taking the 5-alpha reductase inhibitors (5ARI) finasteride and dutasteride.

“These results are exciting because right now there are no drugs to prevent or treat dementia with Lewy bodies,” study investigator Jacob E. Simmering, PhD, of the University of Iowa in Iowa City, said in a press release. “If we can determine that an existing drug can offer protection against this debilitating disease, that has the potential to greatly reduce its effects.”

The findings were published online in Neurology.
 

Increasing ATP Neuroprotective?

In recent years, investigators have speculated that improving metabolic activity in the brain may reduce the risk for Parkinson’s disease (PD). 

In previous studies, the use of Tz/Dz/Az resulted in the activation of phosphoglycerate kinase-1 (PKG1), which increases the availability of adenosine triphosphate (ATP).

There have been case reports of PD being linked to mutations affecting PGK1. Researchers speculate that increased ATP availability in neurons resulting from the activation of PKG1 allows cells to better adapt to aging and synuclein aggregation.

To investigate whether glycolysis-enhancing drugs might be neuroprotective in those with DLB, investigators conducted a retrospective cohort study using a commercial health insurance claims database and a Medicare supplemental health claims database to follow a sample of men aged > 40 years taking Tz, Dz, or Az (n = 126,313), tamsulosin (n = 437,035), or a 5ARI (n = 80,158) for BPH.

Tamsulosin and 5ARI medications do not activate PKG1, so investigators used them as comparators to Tz/Dz/Az. Participants were followed from the medication initiation date until the end of enrollment in the claims databases.

After following claimants for an average of 3 years, 195 participants developed DLB who were taking Tz, Dz, or Az, a rate of 5.21 cases per 10,000 people per year.

During the follow-up period, 1286 participants taking tamsulosin developed DLB, a rate of 10.8 per 10,000 people per year, and among those taking 5ARIs, 193 cases of DLB were reported, a rate of 7.8 per 10,000 people per year.

After matching the groups by age and other health conditions that may explain differences in rates of DLB, men taking Tz/Dz/Az had a 60% lower risk than those taking tamsulosin (P < .001) and a 37% lower risk for developing DLB than those taking the 5ARI medications (P = .012).

“This emerging evidence of a protective association across a spectrum of diseases suggests a broad neuroprotective effect for Tz/Dz/Az, consistent with our hypothesized mechanism that activation of PGK1 increases brain ATP and mitigates neurodegeneration,” the authors wrote.

Study limitations include excluding women from the study, so the findings cannot be generalized to women. Claims analyses were limited to administrative data that could have been incorrect, and the analyses did not include medication dosages.

No study funding or author disclosures were reported.

A version of this article first appeared on Medscape.com.

SAN DIEGO – Researchers are unraveling the complex relationship between cardiovascular (CV)- and stroke-related outcomes in migraine with, and without, aura.

Early results of one study suggest that aura increases the risk for major adverse cerebrovascular and CV events (MACE) in those with migraine, and that this risk is particularly high in men.

“We confirmed that aura increases the risk for these cerebrovascular and cardiovascular outcomes in people with migraine and that there’s an increased risk of these MACE events in men with migraine,” said study investigator Gina Dumkrieger, PhD, principal data science analyst and assistant professor of neurology, Mayo Clinic, Phoenix, Arizona.

The findings were presented at the annual meeting of the American Headache Society.
 

Few Data on Migraine and Stroke Risk

The extent to which migraine increases the risk for stroke CV outcomes has not been extensively studied.

“We’re trying to find out whether migraine-related factors make it more likely that you’re going to have one of these events,” said Dr. Dumkrieger. “Knowing a particular factor increases the risk is something patients and medical providers would want to know.”

Using Mayo Clinic electronic health records, which cover all three sites (Florida, Minnesota, and Arizona), researchers identified individuals with migraine using diagnostic codes. They also looked at data on sex, race, and the presence of aura.

They investigated whether a history of MACE risk factors — including atrial fibrillation, diabetes, hyperlipidemia, hypertension, and tobacco use — affected risk and the potential interaction of aura with these risk factors.

MACE events included cerebral infarction, intracerebral hemorrhage, and acute myocardial infarction.

The analysis included 130,126 participants (80% women, 95% White individuals). Of these, 6% experienced a MACE event, and 94% did not.

“We confirmed that aura does increase the risk for a MACE event, and all of the known risk factors that we included were also significant,” said Dr. Dumkrieger.

Odds ratios (ORs) were 3.82 for atrial fibrillation, 3.11 for hypertension, and 3.06 for hyperlipidemia.

It was surprising, said Dr. Dumkrieger, that male sex was tied to an increased risk for a MACE event (OR, 1.40). “This is not something that was known before,” she said.

The link between migraine and ischemic stroke, particularly with aura, was stronger in women — particularly young women.

Investigators also found an interaction between male sex and aura, when it comes to MACE outcomes, said Dr. Dumkrieger. “Males in general are at higher risk, and people with aura are at higher risk. Males with aura are also at higher risk, but maybe not as much as you would think they would be. It’s not a purely additive thing. This is something we need to look into more,” she said. 

The study also revealed an interaction between aura and hypertension as well as aura and tobacco use, but here too, it was not an additive risk, said Dr. Dumkrieger. However, she added, the presence of aura does not moderate the risk for hyperlipidemia, diabetes, or atrial fibrillation.

The research also showed a significant interaction between male sex and Black race which was additive. “There’s apparently increased risk if you are male and Black or African American that’s greater than what you would expect. We should be especially concerned about these individuals,” she said.
 

Unanswered Questions

The current analysis is part of a larger study that will more closely examine these relationships. “We want to learn, for example, why aura moderates some of the risk factors but not others,” said Dr. Dumkrieger.

The researchers also plan to investigate other migraine features, including headache frequency, and headache sensations such as pulsating or throbbing.

Dr. Dumkrieger was an investigator of another study, also presented at the AHS meeting, that’s investigating the role of migraine-specific features and imaging results in the complex interrelationship between migraine and MACE risk.

That study, which also used the Mayo Clinic electronic health record data, included 60,454 migraine patients diagnosed with migraine after 2010.

Researchers divided participants into those with a MACE outcome (1107) and those without such an outcome (59,347) after at least 2 years of follow-up. They created a propensity cohort of individuals matched for age and risk factors for MACE outcome.

The final cohort consisted of 575 patients with and 652 patients without MACE outcome.

One of the most interesting early results from this study was that those with a MACE outcome had significantly more white matter hyperintensities than those with no MACE outcome, at 64% versus 51%, respectively. 

This and other findings need to be validated in a different cohort with an electronic health records database from another institution. In future, the team plans to focus on identifying specific migraine features and medications and their relative contributions to MACE risk in migraine patients.

Yet another study featured at the AHS meeting confirmed the increased risk for stroke among migraine patients using a large database with over 410,000 subjects.

Results showed stroke was more than three times more common in those with a migraine diagnosis than in those without (risk ratio, [RR] 3.23; P < .001). The RR for hemorrhagic stroke (3.15) was comparable with that of ischemic stroke (3.20).

The overall stroke RR for chronic migraine versus controls without migraine was 3.68 (P < .001). The RR for migraine with aura versus migraine without aura was 1.37 (P < .001).
 

Useful Data

Commenting on the research, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, Arizona, described this new information as “very useful.”

The fact that there are more white matter lesions on MRI scans in migraine patients with MACE needs further exploration, said Dr. VanderPluym.

“Understanding how much of that relates to migraine, how much relates to other comorbid conditions, and what this all means together, is very important, particularly because MACE can be life-threatening and life-altering,” she added.

Learning how migraine medications may impact MACE risk is also something that needs to be examined in greater depth, she said. “I would think that migraines that are controlled might have a different risk for MACE than uncontrolled migraine,” she said.

The investigators reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

SAN DIEGO – Researchers are unraveling the complex relationship between cardiovascular (CV)- and stroke-related outcomes in migraine with, and without, aura.

Early results of one study suggest that aura increases the risk for major adverse cerebrovascular and CV events (MACE) in those with migraine, and that this risk is particularly high in men.

“We confirmed that aura increases the risk for these cerebrovascular and cardiovascular outcomes in people with migraine and that there’s an increased risk of these MACE events in men with migraine,” said study investigator Gina Dumkrieger, PhD, principal data science analyst and assistant professor of neurology, Mayo Clinic, Phoenix, Arizona.

The findings were presented at the annual meeting of the American Headache Society.
 

Few Data on Migraine and Stroke Risk

The extent to which migraine increases the risk for stroke CV outcomes has not been extensively studied.

“We’re trying to find out whether migraine-related factors make it more likely that you’re going to have one of these events,” said Dr. Dumkrieger. “Knowing a particular factor increases the risk is something patients and medical providers would want to know.”

Using Mayo Clinic electronic health records, which cover all three sites (Florida, Minnesota, and Arizona), researchers identified individuals with migraine using diagnostic codes. They also looked at data on sex, race, and the presence of aura.

They investigated whether a history of MACE risk factors — including atrial fibrillation, diabetes, hyperlipidemia, hypertension, and tobacco use — affected risk and the potential interaction of aura with these risk factors.

MACE events included cerebral infarction, intracerebral hemorrhage, and acute myocardial infarction.

The analysis included 130,126 participants (80% women, 95% White individuals). Of these, 6% experienced a MACE event, and 94% did not.

“We confirmed that aura does increase the risk for a MACE event, and all of the known risk factors that we included were also significant,” said Dr. Dumkrieger.

Odds ratios (ORs) were 3.82 for atrial fibrillation, 3.11 for hypertension, and 3.06 for hyperlipidemia.

It was surprising, said Dr. Dumkrieger, that male sex was tied to an increased risk for a MACE event (OR, 1.40). “This is not something that was known before,” she said.

The link between migraine and ischemic stroke, particularly with aura, was stronger in women — particularly young women.

Investigators also found an interaction between male sex and aura, when it comes to MACE outcomes, said Dr. Dumkrieger. “Males in general are at higher risk, and people with aura are at higher risk. Males with aura are also at higher risk, but maybe not as much as you would think they would be. It’s not a purely additive thing. This is something we need to look into more,” she said. 

The study also revealed an interaction between aura and hypertension as well as aura and tobacco use, but here too, it was not an additive risk, said Dr. Dumkrieger. However, she added, the presence of aura does not moderate the risk for hyperlipidemia, diabetes, or atrial fibrillation.

The research also showed a significant interaction between male sex and Black race which was additive. “There’s apparently increased risk if you are male and Black or African American that’s greater than what you would expect. We should be especially concerned about these individuals,” she said.
 

Unanswered Questions

The current analysis is part of a larger study that will more closely examine these relationships. “We want to learn, for example, why aura moderates some of the risk factors but not others,” said Dr. Dumkrieger.

The researchers also plan to investigate other migraine features, including headache frequency, and headache sensations such as pulsating or throbbing.

Dr. Dumkrieger was an investigator of another study, also presented at the AHS meeting, that’s investigating the role of migraine-specific features and imaging results in the complex interrelationship between migraine and MACE risk.

That study, which also used the Mayo Clinic electronic health record data, included 60,454 migraine patients diagnosed with migraine after 2010.

Researchers divided participants into those with a MACE outcome (1107) and those without such an outcome (59,347) after at least 2 years of follow-up. They created a propensity cohort of individuals matched for age and risk factors for MACE outcome.

The final cohort consisted of 575 patients with and 652 patients without MACE outcome.

One of the most interesting early results from this study was that those with a MACE outcome had significantly more white matter hyperintensities than those with no MACE outcome, at 64% versus 51%, respectively. 

This and other findings need to be validated in a different cohort with an electronic health records database from another institution. In future, the team plans to focus on identifying specific migraine features and medications and their relative contributions to MACE risk in migraine patients.

Yet another study featured at the AHS meeting confirmed the increased risk for stroke among migraine patients using a large database with over 410,000 subjects.

Results showed stroke was more than three times more common in those with a migraine diagnosis than in those without (risk ratio, [RR] 3.23; P < .001). The RR for hemorrhagic stroke (3.15) was comparable with that of ischemic stroke (3.20).

The overall stroke RR for chronic migraine versus controls without migraine was 3.68 (P < .001). The RR for migraine with aura versus migraine without aura was 1.37 (P < .001).
 

Useful Data

Commenting on the research, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, Arizona, described this new information as “very useful.”

The fact that there are more white matter lesions on MRI scans in migraine patients with MACE needs further exploration, said Dr. VanderPluym.

“Understanding how much of that relates to migraine, how much relates to other comorbid conditions, and what this all means together, is very important, particularly because MACE can be life-threatening and life-altering,” she added.

Learning how migraine medications may impact MACE risk is also something that needs to be examined in greater depth, she said. “I would think that migraines that are controlled might have a different risk for MACE than uncontrolled migraine,” she said.

The investigators reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

SAN DIEGO – Researchers are unraveling the complex relationship between cardiovascular (CV)- and stroke-related outcomes in migraine with, and without, aura.

Early results of one study suggest that aura increases the risk for major adverse cerebrovascular and CV events (MACE) in those with migraine, and that this risk is particularly high in men.

“We confirmed that aura increases the risk for these cerebrovascular and cardiovascular outcomes in people with migraine and that there’s an increased risk of these MACE events in men with migraine,” said study investigator Gina Dumkrieger, PhD, principal data science analyst and assistant professor of neurology, Mayo Clinic, Phoenix, Arizona.

The findings were presented at the annual meeting of the American Headache Society.
 

Few Data on Migraine and Stroke Risk

The extent to which migraine increases the risk for stroke CV outcomes has not been extensively studied.

“We’re trying to find out whether migraine-related factors make it more likely that you’re going to have one of these events,” said Dr. Dumkrieger. “Knowing a particular factor increases the risk is something patients and medical providers would want to know.”

Using Mayo Clinic electronic health records, which cover all three sites (Florida, Minnesota, and Arizona), researchers identified individuals with migraine using diagnostic codes. They also looked at data on sex, race, and the presence of aura.

They investigated whether a history of MACE risk factors — including atrial fibrillation, diabetes, hyperlipidemia, hypertension, and tobacco use — affected risk and the potential interaction of aura with these risk factors.

MACE events included cerebral infarction, intracerebral hemorrhage, and acute myocardial infarction.

The analysis included 130,126 participants (80% women, 95% White individuals). Of these, 6% experienced a MACE event, and 94% did not.

“We confirmed that aura does increase the risk for a MACE event, and all of the known risk factors that we included were also significant,” said Dr. Dumkrieger.

Odds ratios (ORs) were 3.82 for atrial fibrillation, 3.11 for hypertension, and 3.06 for hyperlipidemia.

It was surprising, said Dr. Dumkrieger, that male sex was tied to an increased risk for a MACE event (OR, 1.40). “This is not something that was known before,” she said.

The link between migraine and ischemic stroke, particularly with aura, was stronger in women — particularly young women.

Investigators also found an interaction between male sex and aura, when it comes to MACE outcomes, said Dr. Dumkrieger. “Males in general are at higher risk, and people with aura are at higher risk. Males with aura are also at higher risk, but maybe not as much as you would think they would be. It’s not a purely additive thing. This is something we need to look into more,” she said. 

The study also revealed an interaction between aura and hypertension as well as aura and tobacco use, but here too, it was not an additive risk, said Dr. Dumkrieger. However, she added, the presence of aura does not moderate the risk for hyperlipidemia, diabetes, or atrial fibrillation.

The research also showed a significant interaction between male sex and Black race which was additive. “There’s apparently increased risk if you are male and Black or African American that’s greater than what you would expect. We should be especially concerned about these individuals,” she said.
 

Unanswered Questions

The current analysis is part of a larger study that will more closely examine these relationships. “We want to learn, for example, why aura moderates some of the risk factors but not others,” said Dr. Dumkrieger.

The researchers also plan to investigate other migraine features, including headache frequency, and headache sensations such as pulsating or throbbing.

Dr. Dumkrieger was an investigator of another study, also presented at the AHS meeting, that’s investigating the role of migraine-specific features and imaging results in the complex interrelationship between migraine and MACE risk.

That study, which also used the Mayo Clinic electronic health record data, included 60,454 migraine patients diagnosed with migraine after 2010.

Researchers divided participants into those with a MACE outcome (1107) and those without such an outcome (59,347) after at least 2 years of follow-up. They created a propensity cohort of individuals matched for age and risk factors for MACE outcome.

The final cohort consisted of 575 patients with and 652 patients without MACE outcome.

One of the most interesting early results from this study was that those with a MACE outcome had significantly more white matter hyperintensities than those with no MACE outcome, at 64% versus 51%, respectively. 

This and other findings need to be validated in a different cohort with an electronic health records database from another institution. In future, the team plans to focus on identifying specific migraine features and medications and their relative contributions to MACE risk in migraine patients.

Yet another study featured at the AHS meeting confirmed the increased risk for stroke among migraine patients using a large database with over 410,000 subjects.

Results showed stroke was more than three times more common in those with a migraine diagnosis than in those without (risk ratio, [RR] 3.23; P < .001). The RR for hemorrhagic stroke (3.15) was comparable with that of ischemic stroke (3.20).

The overall stroke RR for chronic migraine versus controls without migraine was 3.68 (P < .001). The RR for migraine with aura versus migraine without aura was 1.37 (P < .001).
 

Useful Data

Commenting on the research, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, Arizona, described this new information as “very useful.”

The fact that there are more white matter lesions on MRI scans in migraine patients with MACE needs further exploration, said Dr. VanderPluym.

“Understanding how much of that relates to migraine, how much relates to other comorbid conditions, and what this all means together, is very important, particularly because MACE can be life-threatening and life-altering,” she added.

Learning how migraine medications may impact MACE risk is also something that needs to be examined in greater depth, she said. “I would think that migraines that are controlled might have a different risk for MACE than uncontrolled migraine,” she said.

The investigators reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

A version of this article first appeared on Medscape.com.

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

A version of this article first appeared on Medscape.com.

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

A version of this article first appeared on Medscape.com.

TOPLINE:

A new analysis showed that preeclampsia is associated with an increased risk for young-onset dementia.

METHODOLOGY:

• Researchers analyzed data from the French Conception study, a nationwide prospective cohort study of more than 1.9 million pregnancies.
• Mothers were followed for an average of 9 years.

TAKEAWAY:

• Nearly 3% of the mothers had preeclampsia, and 128 developed young-onset dementia.
• Preeclampsia was associated with a 2.65-fold increased risk for young-onset dementia after adjusting for obesity, diabetes, smoking, drug or alcohol addiction, and social deprivation.
• The risk was greater when preeclampsia occurred before 34 weeks of gestation (hazard ratio [HR], 4.15) or was superimposed on chronic hypertension (HR, 4.76).
• Prior research has found an association between preeclampsia and vascular dementia, but this analysis “is the first to show an increase in early-onset dementia risk,” the authors of the study wrote.

IN PRACTICE:

“Individuals who have had preeclampsia should be reassured that young-onset dementia remains a very rare condition. Their absolute risk increases only imperceptibly,” Stephen Tong, PhD, and Roxanne Hastie, PhD, both with the University of Melbourne, Melbourne, Australia, wrote in a related commentary about the findings.

“Individuals who have been affected by preeclampsia in a prior pregnancy might instead focus on reducing their risk of developing the many chronic health ailments that are far more common,” they added. “Although it is yet to be proven in clinical trials, it is plausible that after an episode of preeclampsia, adopting a healthy lifestyle may improve vascular health and reduce the risk of many serious cardiovascular conditions.”

SOURCE:

Valérie Olié, PhD, of the Santé Publique France in Saint-Maurice, France, was the corresponding author on the paper. The research letter was published online in JAMA Network Open.

LIMITATIONS:

The investigators relied on hospital records to identify cases of dementia, which may have led to underestimation of incidence of the disease.

DISCLOSURES:

The study was funded by the French Hypertension Society, the French Hypertension Research Foundation, and the French Cardiology Federation. A co-author disclosed personal fees from pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A new analysis showed that preeclampsia is associated with an increased risk for young-onset dementia.

METHODOLOGY:

• Researchers analyzed data from the French Conception study, a nationwide prospective cohort study of more than 1.9 million pregnancies.
• Mothers were followed for an average of 9 years.

TAKEAWAY:

• Nearly 3% of the mothers had preeclampsia, and 128 developed young-onset dementia.
• Preeclampsia was associated with a 2.65-fold increased risk for young-onset dementia after adjusting for obesity, diabetes, smoking, drug or alcohol addiction, and social deprivation.
• The risk was greater when preeclampsia occurred before 34 weeks of gestation (hazard ratio [HR], 4.15) or was superimposed on chronic hypertension (HR, 4.76).
• Prior research has found an association between preeclampsia and vascular dementia, but this analysis “is the first to show an increase in early-onset dementia risk,” the authors of the study wrote.

IN PRACTICE:

“Individuals who have had preeclampsia should be reassured that young-onset dementia remains a very rare condition. Their absolute risk increases only imperceptibly,” Stephen Tong, PhD, and Roxanne Hastie, PhD, both with the University of Melbourne, Melbourne, Australia, wrote in a related commentary about the findings.

“Individuals who have been affected by preeclampsia in a prior pregnancy might instead focus on reducing their risk of developing the many chronic health ailments that are far more common,” they added. “Although it is yet to be proven in clinical trials, it is plausible that after an episode of preeclampsia, adopting a healthy lifestyle may improve vascular health and reduce the risk of many serious cardiovascular conditions.”

SOURCE:

Valérie Olié, PhD, of the Santé Publique France in Saint-Maurice, France, was the corresponding author on the paper. The research letter was published online in JAMA Network Open.

LIMITATIONS:

The investigators relied on hospital records to identify cases of dementia, which may have led to underestimation of incidence of the disease.

DISCLOSURES:

The study was funded by the French Hypertension Society, the French Hypertension Research Foundation, and the French Cardiology Federation. A co-author disclosed personal fees from pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A new analysis showed that preeclampsia is associated with an increased risk for young-onset dementia.

METHODOLOGY:

• Researchers analyzed data from the French Conception study, a nationwide prospective cohort study of more than 1.9 million pregnancies.
• Mothers were followed for an average of 9 years.

TAKEAWAY:

• Nearly 3% of the mothers had preeclampsia, and 128 developed young-onset dementia.
• Preeclampsia was associated with a 2.65-fold increased risk for young-onset dementia after adjusting for obesity, diabetes, smoking, drug or alcohol addiction, and social deprivation.
• The risk was greater when preeclampsia occurred before 34 weeks of gestation (hazard ratio [HR], 4.15) or was superimposed on chronic hypertension (HR, 4.76).
• Prior research has found an association between preeclampsia and vascular dementia, but this analysis “is the first to show an increase in early-onset dementia risk,” the authors of the study wrote.

IN PRACTICE:

“Individuals who have had preeclampsia should be reassured that young-onset dementia remains a very rare condition. Their absolute risk increases only imperceptibly,” Stephen Tong, PhD, and Roxanne Hastie, PhD, both with the University of Melbourne, Melbourne, Australia, wrote in a related commentary about the findings.

“Individuals who have been affected by preeclampsia in a prior pregnancy might instead focus on reducing their risk of developing the many chronic health ailments that are far more common,” they added. “Although it is yet to be proven in clinical trials, it is plausible that after an episode of preeclampsia, adopting a healthy lifestyle may improve vascular health and reduce the risk of many serious cardiovascular conditions.”

SOURCE:

Valérie Olié, PhD, of the Santé Publique France in Saint-Maurice, France, was the corresponding author on the paper. The research letter was published online in JAMA Network Open.

LIMITATIONS:

The investigators relied on hospital records to identify cases of dementia, which may have led to underestimation of incidence of the disease.

DISCLOSURES:

The study was funded by the French Hypertension Society, the French Hypertension Research Foundation, and the French Cardiology Federation. A co-author disclosed personal fees from pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

An algorithm using two well-known tests has shown strong accuracy (91%) in predicting whether an older driver can pass an on-road driving evaluation according to a new study published in the Journal of the American Medical Directors Association .

The Fit2Drive algorithm combines the Mini-Mental State Exam (MMSE), a 30-point dementia screening tool that has been found in several studies to have an association with driving ability, and the Trails B test, which gauges cognitive flexibility and set-shifting (task switching), considered to be measures of executive functioning.
 

Algorithm Available for Providers

The algorithm is clinically available and providers can fill in patients’ information and results of the two tests at the Fit2Drive website. Results may help physicians with often-difficult conversations with older patients about driving when they present with cognitive concerns.

Families report it is one of the most difficult conversations they have with a loved one and doctors are often asked to be part of the conversation. This is particularly difficult when, often, little objective information is available. In the past, a clinical rule of thumb has been that people diagnosed with Alzheimer’s disease or related dementias (ADRD) will usually be able to drive for 3 years after diagnosis.

“[T]he anger, tears, and frustration on the part of the individual patient and the lack of objective data to guide provider recommendations are the driving forces behind our effort to develop a highly accurate, evidence-based predictor of the ability to pass an on-road driving test,” the authors write. They added that the goal of the study was to identify the smallest number of cognitive test results that could predict likelihood of passing an on-road driver evaluation.

A number of tests were evaluated for the algorithm, but the combination of Trails B in seconds and MMSE using the highest scores of the serial 7s (counting back from 100 by 7s) or WORLD spelled backward accounted for the highest correlation with passing the on-road driving test, according to the authors, led by Ruth Tappen, EdD, FN, with the Christine E. Lynn College of Nursing at Florida Atlantic University, in Boca Raton.

A receiver operator characteristic (ROC) analysis was conducted on the linear combination of the two assessments.

“Because an ROC of 0.70 is considered to be the minimal requirement [for predictive value], 0.80 is considered good, and higher than 0.90 is excellent, these findings [with 91% area under the curve] suggest excellent accuracy using these two cognitive tests in this population,” the authors write.

For this analysis, researchers included 412 older drivers (179 men and 233 women) with an average age of 80. T he study was conducted at the Florida Atlantic University’s Memory Center and Clinical Research Unit. Participants included those who received a driving evaluation at the Memory Center and agreed to have their results included in the Driving Repository, and community-based older drivers who volunteered to participate.
 

Limitations of the Study

There were marginal differences between sexes on the measures, but they were not significant. The sample was composed of relatively well-educated people, primarily of European American ethnic origin, which is a consideration in generalizing the results.

Among other limitations are that physical and sensory factors, in addition to cognitive issues, may affect an individual’s ability to drive safely and are not included in the algorithm. Sensory disabilities, including reduced visual acuity caused by binocular field vision loss, contrast sensitivity, glare sensitivity, and other conditions, may affect driving ability as well as the ability to fully rotate the head and neck. Medical conditions affecting the cardiovascular, neurological, and orthopedic systems can also influence driving ability.

“Future studies should involve more diverse samples and a greater variety of driving challenges, including school zones and multilane highways, which are not included in the study,” the authors write.

The study received grant support from the State of Florida Department of Health and the Ed and Ethel Moore Alzheimer’s Disease Research Program.

An algorithm using two well-known tests has shown strong accuracy (91%) in predicting whether an older driver can pass an on-road driving evaluation according to a new study published in the Journal of the American Medical Directors Association .

The Fit2Drive algorithm combines the Mini-Mental State Exam (MMSE), a 30-point dementia screening tool that has been found in several studies to have an association with driving ability, and the Trails B test, which gauges cognitive flexibility and set-shifting (task switching), considered to be measures of executive functioning.
 

Algorithm Available for Providers

The algorithm is clinically available and providers can fill in patients’ information and results of the two tests at the Fit2Drive website. Results may help physicians with often-difficult conversations with older patients about driving when they present with cognitive concerns.

Families report it is one of the most difficult conversations they have with a loved one and doctors are often asked to be part of the conversation. This is particularly difficult when, often, little objective information is available. In the past, a clinical rule of thumb has been that people diagnosed with Alzheimer’s disease or related dementias (ADRD) will usually be able to drive for 3 years after diagnosis.

“[T]he anger, tears, and frustration on the part of the individual patient and the lack of objective data to guide provider recommendations are the driving forces behind our effort to develop a highly accurate, evidence-based predictor of the ability to pass an on-road driving test,” the authors write. They added that the goal of the study was to identify the smallest number of cognitive test results that could predict likelihood of passing an on-road driver evaluation.

A number of tests were evaluated for the algorithm, but the combination of Trails B in seconds and MMSE using the highest scores of the serial 7s (counting back from 100 by 7s) or WORLD spelled backward accounted for the highest correlation with passing the on-road driving test, according to the authors, led by Ruth Tappen, EdD, FN, with the Christine E. Lynn College of Nursing at Florida Atlantic University, in Boca Raton.

A receiver operator characteristic (ROC) analysis was conducted on the linear combination of the two assessments.

“Because an ROC of 0.70 is considered to be the minimal requirement [for predictive value], 0.80 is considered good, and higher than 0.90 is excellent, these findings [with 91% area under the curve] suggest excellent accuracy using these two cognitive tests in this population,” the authors write.

For this analysis, researchers included 412 older drivers (179 men and 233 women) with an average age of 80. T he study was conducted at the Florida Atlantic University’s Memory Center and Clinical Research Unit. Participants included those who received a driving evaluation at the Memory Center and agreed to have their results included in the Driving Repository, and community-based older drivers who volunteered to participate.
 

Limitations of the Study

There were marginal differences between sexes on the measures, but they were not significant. The sample was composed of relatively well-educated people, primarily of European American ethnic origin, which is a consideration in generalizing the results.

Among other limitations are that physical and sensory factors, in addition to cognitive issues, may affect an individual’s ability to drive safely and are not included in the algorithm. Sensory disabilities, including reduced visual acuity caused by binocular field vision loss, contrast sensitivity, glare sensitivity, and other conditions, may affect driving ability as well as the ability to fully rotate the head and neck. Medical conditions affecting the cardiovascular, neurological, and orthopedic systems can also influence driving ability.

“Future studies should involve more diverse samples and a greater variety of driving challenges, including school zones and multilane highways, which are not included in the study,” the authors write.

The study received grant support from the State of Florida Department of Health and the Ed and Ethel Moore Alzheimer’s Disease Research Program.

An algorithm using two well-known tests has shown strong accuracy (91%) in predicting whether an older driver can pass an on-road driving evaluation according to a new study published in the Journal of the American Medical Directors Association .

The Fit2Drive algorithm combines the Mini-Mental State Exam (MMSE), a 30-point dementia screening tool that has been found in several studies to have an association with driving ability, and the Trails B test, which gauges cognitive flexibility and set-shifting (task switching), considered to be measures of executive functioning.
 

Algorithm Available for Providers

The algorithm is clinically available and providers can fill in patients’ information and results of the two tests at the Fit2Drive website. Results may help physicians with often-difficult conversations with older patients about driving when they present with cognitive concerns.

Families report it is one of the most difficult conversations they have with a loved one and doctors are often asked to be part of the conversation. This is particularly difficult when, often, little objective information is available. In the past, a clinical rule of thumb has been that people diagnosed with Alzheimer’s disease or related dementias (ADRD) will usually be able to drive for 3 years after diagnosis.

“[T]he anger, tears, and frustration on the part of the individual patient and the lack of objective data to guide provider recommendations are the driving forces behind our effort to develop a highly accurate, evidence-based predictor of the ability to pass an on-road driving test,” the authors write. They added that the goal of the study was to identify the smallest number of cognitive test results that could predict likelihood of passing an on-road driver evaluation.

A number of tests were evaluated for the algorithm, but the combination of Trails B in seconds and MMSE using the highest scores of the serial 7s (counting back from 100 by 7s) or WORLD spelled backward accounted for the highest correlation with passing the on-road driving test, according to the authors, led by Ruth Tappen, EdD, FN, with the Christine E. Lynn College of Nursing at Florida Atlantic University, in Boca Raton.

A receiver operator characteristic (ROC) analysis was conducted on the linear combination of the two assessments.

“Because an ROC of 0.70 is considered to be the minimal requirement [for predictive value], 0.80 is considered good, and higher than 0.90 is excellent, these findings [with 91% area under the curve] suggest excellent accuracy using these two cognitive tests in this population,” the authors write.

For this analysis, researchers included 412 older drivers (179 men and 233 women) with an average age of 80. T he study was conducted at the Florida Atlantic University’s Memory Center and Clinical Research Unit. Participants included those who received a driving evaluation at the Memory Center and agreed to have their results included in the Driving Repository, and community-based older drivers who volunteered to participate.
 

Limitations of the Study

There were marginal differences between sexes on the measures, but they were not significant. The sample was composed of relatively well-educated people, primarily of European American ethnic origin, which is a consideration in generalizing the results.

Among other limitations are that physical and sensory factors, in addition to cognitive issues, may affect an individual’s ability to drive safely and are not included in the algorithm. Sensory disabilities, including reduced visual acuity caused by binocular field vision loss, contrast sensitivity, glare sensitivity, and other conditions, may affect driving ability as well as the ability to fully rotate the head and neck. Medical conditions affecting the cardiovascular, neurological, and orthopedic systems can also influence driving ability.

“Future studies should involve more diverse samples and a greater variety of driving challenges, including school zones and multilane highways, which are not included in the study,” the authors write.

The study received grant support from the State of Florida Department of Health and the Ed and Ethel Moore Alzheimer’s Disease Research Program.

TOPLINE:

Men with immunoglobulin G4 (IgG4)-related disease exhibit significantly lower serum lipase levels and a greater likelihood of organ involvement than women, highlighting significant sex-dependent differences in disease manifestations.

METHODOLOGY:

• Researchers conducted a retrospective study of 328 patients (69% men) diagnosed with IgG4-related disease at the Massachusetts General Hospital – Rheumatology Clinic, Boston, who met the American College of Rheumatology–European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria between January 2008 and May 2023.
• Among the 328 patients, 69% were men and 31% were women, with a significant male-to-female ratio of 2.2:1.0. Men were typically older at diagnosis (median age, 63.7 vs 58.2 years).
• Data on serum lipase levels, renal involvement, and other clinical and laboratory parameters were collected.

TAKEAWAY:

• Men had higher baseline ACR-EULAR scores, indicating more severe disease (median score of 35.0 vs 29.5; P = .0010).
• Male patients demonstrated a median baseline serum lipase concentration of 24.5 U/L, significantly lower than the 33.5 U/L observed in women.
• Pancreatic (50% vs 26%) or renal (36% vs 18%) involvement was more common in men.
• Men exhibited higher IgG4 levels (P = .0050) and active B-cell responses in the blood (P = .0095).

IN PRACTICE:

According to the authors, this work confirms “the impression of an important sex disparity among patients with IgG4-related disease, with most patients being male, and male patients demonstrating strong tendencies toward more severe disease than female patients.”

SOURCE:

The study was led by Isha Jha, MD, Massachusetts General Hospital, Boston. It was published online on May 30, 2024, in The Lancet Rheumatology. 

LIMITATIONS:

The study’s retrospective design may limit the ability to establish causality between sex differences and IgG4-related disease manifestations. A relatively small percentage of patients were assessed before receiving any immunosuppressive treatment, potentially influencing the observed clinical parameters.

DISCLOSURES:

This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors declared financial ties outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Men with immunoglobulin G4 (IgG4)-related disease exhibit significantly lower serum lipase levels and a greater likelihood of organ involvement than women, highlighting significant sex-dependent differences in disease manifestations.

METHODOLOGY:

• Researchers conducted a retrospective study of 328 patients (69% men) diagnosed with IgG4-related disease at the Massachusetts General Hospital – Rheumatology Clinic, Boston, who met the American College of Rheumatology–European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria between January 2008 and May 2023.
• Among the 328 patients, 69% were men and 31% were women, with a significant male-to-female ratio of 2.2:1.0. Men were typically older at diagnosis (median age, 63.7 vs 58.2 years).
• Data on serum lipase levels, renal involvement, and other clinical and laboratory parameters were collected.

TAKEAWAY:

• Men had higher baseline ACR-EULAR scores, indicating more severe disease (median score of 35.0 vs 29.5; P = .0010).
• Male patients demonstrated a median baseline serum lipase concentration of 24.5 U/L, significantly lower than the 33.5 U/L observed in women.
• Pancreatic (50% vs 26%) or renal (36% vs 18%) involvement was more common in men.
• Men exhibited higher IgG4 levels (P = .0050) and active B-cell responses in the blood (P = .0095).

IN PRACTICE:

According to the authors, this work confirms “the impression of an important sex disparity among patients with IgG4-related disease, with most patients being male, and male patients demonstrating strong tendencies toward more severe disease than female patients.”

SOURCE:

The study was led by Isha Jha, MD, Massachusetts General Hospital, Boston. It was published online on May 30, 2024, in The Lancet Rheumatology. 

LIMITATIONS:

The study’s retrospective design may limit the ability to establish causality between sex differences and IgG4-related disease manifestations. A relatively small percentage of patients were assessed before receiving any immunosuppressive treatment, potentially influencing the observed clinical parameters.

DISCLOSURES:

This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors declared financial ties outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Men with immunoglobulin G4 (IgG4)-related disease exhibit significantly lower serum lipase levels and a greater likelihood of organ involvement than women, highlighting significant sex-dependent differences in disease manifestations.

METHODOLOGY:

• Researchers conducted a retrospective study of 328 patients (69% men) diagnosed with IgG4-related disease at the Massachusetts General Hospital – Rheumatology Clinic, Boston, who met the American College of Rheumatology–European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria between January 2008 and May 2023.
• Among the 328 patients, 69% were men and 31% were women, with a significant male-to-female ratio of 2.2:1.0. Men were typically older at diagnosis (median age, 63.7 vs 58.2 years).
• Data on serum lipase levels, renal involvement, and other clinical and laboratory parameters were collected.

TAKEAWAY:

• Men had higher baseline ACR-EULAR scores, indicating more severe disease (median score of 35.0 vs 29.5; P = .0010).
• Male patients demonstrated a median baseline serum lipase concentration of 24.5 U/L, significantly lower than the 33.5 U/L observed in women.
• Pancreatic (50% vs 26%) or renal (36% vs 18%) involvement was more common in men.
• Men exhibited higher IgG4 levels (P = .0050) and active B-cell responses in the blood (P = .0095).

IN PRACTICE:

According to the authors, this work confirms “the impression of an important sex disparity among patients with IgG4-related disease, with most patients being male, and male patients demonstrating strong tendencies toward more severe disease than female patients.”

SOURCE:

The study was led by Isha Jha, MD, Massachusetts General Hospital, Boston. It was published online on May 30, 2024, in The Lancet Rheumatology. 

LIMITATIONS:

The study’s retrospective design may limit the ability to establish causality between sex differences and IgG4-related disease manifestations. A relatively small percentage of patients were assessed before receiving any immunosuppressive treatment, potentially influencing the observed clinical parameters.

DISCLOSURES:

This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors declared financial ties outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

In October 2023, Robert Card — a grenade instructor in the Army Reserve — shot and killed 18 people in Maine, before turning the gun on himself. As reported by The New York Times, his family said that he had become increasingly erratic and violent during the months before the rampage.

A postmortem conducted by the Chronic Traumatic Encephalopathy (CTE) Center at Boston University found “significant evidence of traumatic brain injuries” [TBIs] and “significant degeneration, axonal and myelin loss, inflammation, and small blood vessel injury” in the white matter, the center’s director, Ann McKee, MD, said in a press release. “These findings align with our previous studies on the effects of blast injury in humans and experimental models.”

Members of the military, such as Mr. Card, are exposed to blasts from repeated firing of heavy weapons not only during combat but also during training.

New data suggest that repeated blast exposure may impair the brain’s waste clearance system, leading to biomarker changes indicative of preclinical Alzheimer’s disease 20 years earlier than typical. A higher index of suspicion for dementia or Alzheimer’s disease may be warranted in patients with a history of blast exposure or subconcussive brain injury who present with cognitive issues, according to experts interviewed.

In 2022, the US Department of Defense (DOD) launched its Warfighter Brain Health Initiative with the aim of “optimizing service member brain health and countering traumatic brain injuries.”

In April 2024, the Blast Overpressure Safety Act was introduced in the Senate to require the DOD to enact better blast screening, tracking, prevention, and treatment. The DOD initiated 26 blast overpressure studies.

Heather Snyder, PhD, Alzheimer’s Association vice president of Medical and Scientific Relations, said that an important component of that research involves “the need to study the difference between TBI-caused dementia and dementia caused independently” and “the need to study biomarkers to better understand the long-term consequences of TBI.”
 

What Is the Underlying Biology?

Dr. Snyder was the lead author of a white paper produced by the Alzheimer’s Association in 2018 on military-related risk factors for Alzheimer’s disease and related dementias. “There is a lot of work trying to understand the effect of pure blast waves on the brain, as opposed to the actual impact of the injury,” she said.

The white paper speculated that blast exposure may be analogous to subconcussive brain injury in athletes where there are no obvious immediate clinical symptoms or neurological dysfunction but which can cause cumulative injury and functional impairment over time.

“We are also trying to understand the underlying biology around brain changes, such as accumulation of tau and amyloid and other specific markers related to brain changes in Alzheimer’s disease,” said Dr. Snyder, chair of the Peer Reviewed Alzheimer’s Research Program Programmatic Panel for Alzheimer’s Disease/Alzheimer’s Disease and Related Dementias and TBI.
 

Common Biomarker Signatures

A recent study in Neurology comparing 51 veterans with mild TBI (mTBI) with 85 veterans and civilians with no lifetime history of TBI is among the first to explore these biomarker changes in human beings.

“Our findings suggest that chronic neuropathologic processes associated with blast mTBI share properties in common with pathogenic processes that are precursors to Alzheimer’s disease onset,” said coauthor Elaine R. Peskind, MD, professor of psychiatry and behavioral sciences, University of Washington, Seattle.

The largely male participants were a mean age of 34 years and underwent standardized clinical and neuropsychological testing as well as lumbar puncture to collect cerebrospinal fluid (CSF). The mTBI group had experienced at least one war zone blast or combined blast/impact that met criteria for mTBI, but 91% had more than one blast mTBI, and the study took place over 13 years.

The researchers found that the mTBI group “had biomarker signatures in common with the earliest stages of Alzheimer’s disease,” said Dr. Peskind.

For example, at age 50, they had lower mean levels of CSF amyloid beta 42 (Abeta42), the earliest marker of brain parenchymal Abeta deposition, compared with the control group (154 pg/mL and 1864 pg/mL lower, respectively).

High CSF phosphorylated tau181 (p-tau181) and total tau are established biomarkers for Alzheimer’s disease. However, levels of these biomarkers remained “relatively constant with age” in participants with mTBI but were higher in older ages for the non-TBI group.

The mTBI group also showed worse cognitive performance at older ages (P < .08). Poorer verbal memory and verbal fluency performance were associated with lower CSF Abeta42 in older participants (P ≤ .05).

In Alzheimer’s disease, a reduction in CSF Abeta42 may occur up to 20 years before the onset of clinical symptoms, according to Dr. Peskind. “But what we don’t know from this study is what this means, as total tau protein and p-tau181 in the CSF were also low, which isn’t entirely typical in the picture of preclinical Alzheimer’s disease,” she said. However, changes in total tau and p-tau181 lag behind changes in Abeta42.
 

Is Impaired Clearance the Culprit?

Coauthor Jeffrey Iliff, PhD, professor, University of Washington Department of Psychiatry and Behavioral Sciences and University of Washington Department of Neurology, Seattle, elaborated.

“In the setting of Alzheimer’s disease, a signature of the disease is reduced CSF Abeta42, which is thought to reflect that much of the amyloid gets ‘stuck’ in the brain in the form of amyloid plaques,” he said. “There are usually higher levels of phosphorylated tau and total tau, which are thought to reflect the presence of tau tangles and degeneration of neurons in the brain. But in this study, all of those were lowered, which is not exactly an Alzheimer’s disease profile.”

Dr. Iliff, associate director for research, VA Northwest Mental Illness Research, Education, and Clinical Center at VA Puget Sound Health Care System, Seattle, suggested that the culprit may be impairment in the brain’s glymphatic system. “Recently described biological research supports [the concept of] clearance of waste out of the brain during sleep via the glymphatic system, with amyloid and tau being cleared from the brain interstitium during sleep.”

A recent hypothesis is that blast TBI impairs that process. “This is why we see less of those proteins in the CSF. They’re not being cleared, which might contribute downstream to the clumping up of protein in the brain,” he suggested.

The evidence base corroborating that hypothesis is in its infancy; however, new research conducted by Dr. Iliff and his colleagues sheds light on this potential mechanism.

In blast TBI, energy from the explosion and resulting overpressure wave are “transmitted through the brain, which causes tissues of different densities — such as gray and white matter — to accelerate at different rates,” according to Dr. Iliff. This results in the shearing and stretching of brain tissue, leading to a “diffuse pattern of tissue damage.”

It is known that blast TBI has clinical overlap and associations with posttraumatic stress disorder (PTSD), depression, and persistent neurobehavioral symptoms; that veterans with a history of TBI are more than twice as likely to die by suicide than veterans with no TBI history; and that TBI may increase the risk for Alzheimer’s disease and related dementing disorders, as well as CTE.

The missing link may be the glymphatic system — a “brain-wide network of perivascular pathways, along which CSF and interstitial fluid (ISF) exchange, supporting the clearance of interstitial solutes, including amyloid-beta.”

Dr. Iliff and his group previously found that glymphatic function is “markedly and chronically impaired” following impact TBI in mice and that this impairment is associated with the mislocalization of astroglial aquaporin 4 (AQP4), a water channel that lines perivascular spaces and plays a role in healthy glymphatic exchange.

In their new study, the researchers examined both the expression and the localization of AQP4 in the human postmortem frontal cortex and found “distinct laminar differences” in AQP4 expression following blast exposure. They observed similar changes as well as impairment of glymphatic function, which emerged 28 days following blast injury in a mouse model of repetitive blast mTBI.

And in a cohort of veterans with blast mTBI, blast exposure was found to be associated with an increased burden of frontal cortical MRI-visible perivascular spaces — a “putative neuroimaging marker” of glymphatic perivascular dysfunction.

The earlier Neurology study “showed impairment of biomarkers in the CSF, but the new study showed ‘why’ or ‘how’ these biomarkers are impaired, which is via impairment of the glymphatic clearance process,” Dr. Iliff explained.
 

Veterans Especially Vulnerable

Dr. Peskind, co-director of the VA Northwest Mental Illness Research, Education and Clinical Center, VA Puget Sound Health Care System, noted that while the veterans in the earlier study had at least one TBI, the average number was 20, and it was more common to have more than 50 mTBIs than to have a single one.

“These were highly exposed combat vets,” she said. “And that number doesn’t even account for subconcussive exposure to blasts, which now appear to cause detectable brain damage, even in the absence of a diagnosable TBI.”

The Maine shooter, Mr. Card, had not seen combat and was not assessed for TBI during a psychiatric hospitalization, according to The New York Times.

Dr. Peskind added that this type of blast damage is likely specific to individuals in the military. “It isn’t the sound that causes the damage,” she explained. “It’s the blast wave, the pressure wave, and there aren’t a lot of other occupations that have those types of occupational exposures.”

Dr. Snyder added that the majority of blast TBIs have been studied in military personnel, and she is not aware of studies that have looked at blast injuries in other industries, such as demolition or mining, to see if they have the same type of biologic consequences.

Dr. Snyder hopes that the researchers will follow the participants in the Neurology study and continue looking at specific markers related to Alzheimer’s disease brain changes. What the research so far shows “is that, at an earlier age, we’re starting to see those markers changing, suggesting that the underlying biology in people with mild blast TBI is similar to the underlying biology in Alzheimer’s disease as well.”

Michael Alosco, PhD, associate professor and vice chair of research, department of neurology, Boston University Chobanian & Avedisian School of Medicine, called the issue of blast exposure and TBI “a very complex and nuanced topic,” especially because TBI is “considered a risk factor of Alzheimer’s disease” and “different types of TBIs could trigger distinct pathophysiologic processes; however, the long-term impact of repetitive blast TBIs on neurodegenerative disease changes remains unknown.”

He coauthored an editorial on the earlier Neurology study that noted its limitations, such as a small sample size and lack of consideration of lifestyle and health factors but acknowledged that the “findings provide preliminary evidence that repetitive blast exposures might influence beta-amyloid accumulation.”
 

Clinical Implications

For Dr. Peskind, the “inflection point” was seeing lower CSF Abeta42, about 20 years earlier than ages 60 and 70, which is more typical in cognitively normal community volunteers.

But she described herself as “loath to say that veterans or service members have a 20-year acceleration of risk of Alzheimer’s disease,” adding, “I don’t want to scare the heck out of our service members of veterans.” Although “this is what we fear, we’re not ready to say it for sure yet because we need to do more work. Nevertheless, it does increase the index of suspicion.”

The clinical take-home messages are not unique to service members or veterans or people with a history of head injuries or a genetic predisposition to Alzheimer’s disease, she emphasized. “If anyone of any age or occupation comes in with cognitive issues, such as [impaired] memory or executive function, they deserve a workup for dementing disorders.” Frontotemporal dementia, for example, can present earlier than Alzheimer’s disease typically does.

Common comorbidities with TBI are PTSD and obstructive sleep apnea (OSA), which can also cause cognitive issues and are also risk factors for dementia.

Dr. Iliff agreed. “If you see a veteran with a history of PTSD, a history of blast TBI, and a history of OSA or some combination of those three, I recommend having a higher index of suspicion [for potential dementia] than for an average person without any of these, even at a younger age than one would ordinarily expect.”

Of all of these factors, the only truly directly modifiable one is sleep disruption, including that caused by OSA or sleep disorders related to PTSD, he added. “Epidemiologic data suggest a connection particularly between midlife sleep disruption and the risk of dementia and Alzheimer’s disease, and so it’s worth thinking about sleep as a modifiable risk factor even as early as the 40s and 50s, whether the patient is or isn’t a veteran.”

Dr. Peskind recommended asking patients, “Do they snore? Do they thrash about during sleep? Do they have trauma nightmares? This will inform the type of intervention required.”

Dr. Alosco added that there is no known “safe” threshold of exposure to blasts, and that thresholds are “unclear, particularly at the individual level.” In American football, there is a dose-response relationship between years of play and risk for later-life neurological disorder. “The best way to mitigate risk is to limit cumulative exposure,” he said.

The study by Li and colleagues was funded by grant funding from the Department of Veterans Affairs Rehabilitation Research and Development Service and the University of Washington Friends of Alzheimer’s Research. Other sources of funding to individual researchers are listed in the original paper. The study by Braun and colleagues was supported by the National Heart, Lung and Blood Institute; the Department of Veterans Affairs Rehabilitation Research and Development Service; and the National Institute on Aging. The white paper included studies that received funding from numerous sources, including the National Institutes of Health and the DOD. Dr. Iliff serves as the chair of the Scientific Advisory Board for Applied Cognition Inc., from which he receives compensation and in which he holds an equity stake. In the last year, he served as a paid consultant to Gryphon Biosciences. Dr. Peskind has served as a paid consultant to the companies Genentech, Roche, and Alpha Cognition. Dr. Alosco was supported by grant funding from the NIH; he received research support from Rainwater Charitable Foundation Inc., and Life Molecular Imaging Inc.; he has received a single honorarium from the Michael J. Fox Foundation for services unrelated to this editorial; and he received royalties from Oxford University Press Inc. The other authors’ disclosures are listed in the original papers.
 

A version of this article appeared on Medscape.com.

In October 2023, Robert Card — a grenade instructor in the Army Reserve — shot and killed 18 people in Maine, before turning the gun on himself. As reported by The New York Times, his family said that he had become increasingly erratic and violent during the months before the rampage.

A postmortem conducted by the Chronic Traumatic Encephalopathy (CTE) Center at Boston University found “significant evidence of traumatic brain injuries” [TBIs] and “significant degeneration, axonal and myelin loss, inflammation, and small blood vessel injury” in the white matter, the center’s director, Ann McKee, MD, said in a press release. “These findings align with our previous studies on the effects of blast injury in humans and experimental models.”

Members of the military, such as Mr. Card, are exposed to blasts from repeated firing of heavy weapons not only during combat but also during training.

New data suggest that repeated blast exposure may impair the brain’s waste clearance system, leading to biomarker changes indicative of preclinical Alzheimer’s disease 20 years earlier than typical. A higher index of suspicion for dementia or Alzheimer’s disease may be warranted in patients with a history of blast exposure or subconcussive brain injury who present with cognitive issues, according to experts interviewed.

In 2022, the US Department of Defense (DOD) launched its Warfighter Brain Health Initiative with the aim of “optimizing service member brain health and countering traumatic brain injuries.”

In April 2024, the Blast Overpressure Safety Act was introduced in the Senate to require the DOD to enact better blast screening, tracking, prevention, and treatment. The DOD initiated 26 blast overpressure studies.

Heather Snyder, PhD, Alzheimer’s Association vice president of Medical and Scientific Relations, said that an important component of that research involves “the need to study the difference between TBI-caused dementia and dementia caused independently” and “the need to study biomarkers to better understand the long-term consequences of TBI.”
 

What Is the Underlying Biology?

Dr. Snyder was the lead author of a white paper produced by the Alzheimer’s Association in 2018 on military-related risk factors for Alzheimer’s disease and related dementias. “There is a lot of work trying to understand the effect of pure blast waves on the brain, as opposed to the actual impact of the injury,” she said.

The white paper speculated that blast exposure may be analogous to subconcussive brain injury in athletes where there are no obvious immediate clinical symptoms or neurological dysfunction but which can cause cumulative injury and functional impairment over time.

“We are also trying to understand the underlying biology around brain changes, such as accumulation of tau and amyloid and other specific markers related to brain changes in Alzheimer’s disease,” said Dr. Snyder, chair of the Peer Reviewed Alzheimer’s Research Program Programmatic Panel for Alzheimer’s Disease/Alzheimer’s Disease and Related Dementias and TBI.
 

Common Biomarker Signatures

A recent study in Neurology comparing 51 veterans with mild TBI (mTBI) with 85 veterans and civilians with no lifetime history of TBI is among the first to explore these biomarker changes in human beings.

“Our findings suggest that chronic neuropathologic processes associated with blast mTBI share properties in common with pathogenic processes that are precursors to Alzheimer’s disease onset,” said coauthor Elaine R. Peskind, MD, professor of psychiatry and behavioral sciences, University of Washington, Seattle.

The largely male participants were a mean age of 34 years and underwent standardized clinical and neuropsychological testing as well as lumbar puncture to collect cerebrospinal fluid (CSF). The mTBI group had experienced at least one war zone blast or combined blast/impact that met criteria for mTBI, but 91% had more than one blast mTBI, and the study took place over 13 years.

The researchers found that the mTBI group “had biomarker signatures in common with the earliest stages of Alzheimer’s disease,” said Dr. Peskind.

For example, at age 50, they had lower mean levels of CSF amyloid beta 42 (Abeta42), the earliest marker of brain parenchymal Abeta deposition, compared with the control group (154 pg/mL and 1864 pg/mL lower, respectively).

High CSF phosphorylated tau181 (p-tau181) and total tau are established biomarkers for Alzheimer’s disease. However, levels of these biomarkers remained “relatively constant with age” in participants with mTBI but were higher in older ages for the non-TBI group.

The mTBI group also showed worse cognitive performance at older ages (P < .08). Poorer verbal memory and verbal fluency performance were associated with lower CSF Abeta42 in older participants (P ≤ .05).

In Alzheimer’s disease, a reduction in CSF Abeta42 may occur up to 20 years before the onset of clinical symptoms, according to Dr. Peskind. “But what we don’t know from this study is what this means, as total tau protein and p-tau181 in the CSF were also low, which isn’t entirely typical in the picture of preclinical Alzheimer’s disease,” she said. However, changes in total tau and p-tau181 lag behind changes in Abeta42.
 

Is Impaired Clearance the Culprit?

Coauthor Jeffrey Iliff, PhD, professor, University of Washington Department of Psychiatry and Behavioral Sciences and University of Washington Department of Neurology, Seattle, elaborated.

“In the setting of Alzheimer’s disease, a signature of the disease is reduced CSF Abeta42, which is thought to reflect that much of the amyloid gets ‘stuck’ in the brain in the form of amyloid plaques,” he said. “There are usually higher levels of phosphorylated tau and total tau, which are thought to reflect the presence of tau tangles and degeneration of neurons in the brain. But in this study, all of those were lowered, which is not exactly an Alzheimer’s disease profile.”

Dr. Iliff, associate director for research, VA Northwest Mental Illness Research, Education, and Clinical Center at VA Puget Sound Health Care System, Seattle, suggested that the culprit may be impairment in the brain’s glymphatic system. “Recently described biological research supports [the concept of] clearance of waste out of the brain during sleep via the glymphatic system, with amyloid and tau being cleared from the brain interstitium during sleep.”

A recent hypothesis is that blast TBI impairs that process. “This is why we see less of those proteins in the CSF. They’re not being cleared, which might contribute downstream to the clumping up of protein in the brain,” he suggested.

The evidence base corroborating that hypothesis is in its infancy; however, new research conducted by Dr. Iliff and his colleagues sheds light on this potential mechanism.

In blast TBI, energy from the explosion and resulting overpressure wave are “transmitted through the brain, which causes tissues of different densities — such as gray and white matter — to accelerate at different rates,” according to Dr. Iliff. This results in the shearing and stretching of brain tissue, leading to a “diffuse pattern of tissue damage.”

It is known that blast TBI has clinical overlap and associations with posttraumatic stress disorder (PTSD), depression, and persistent neurobehavioral symptoms; that veterans with a history of TBI are more than twice as likely to die by suicide than veterans with no TBI history; and that TBI may increase the risk for Alzheimer’s disease and related dementing disorders, as well as CTE.

The missing link may be the glymphatic system — a “brain-wide network of perivascular pathways, along which CSF and interstitial fluid (ISF) exchange, supporting the clearance of interstitial solutes, including amyloid-beta.”

Dr. Iliff and his group previously found that glymphatic function is “markedly and chronically impaired” following impact TBI in mice and that this impairment is associated with the mislocalization of astroglial aquaporin 4 (AQP4), a water channel that lines perivascular spaces and plays a role in healthy glymphatic exchange.

In their new study, the researchers examined both the expression and the localization of AQP4 in the human postmortem frontal cortex and found “distinct laminar differences” in AQP4 expression following blast exposure. They observed similar changes as well as impairment of glymphatic function, which emerged 28 days following blast injury in a mouse model of repetitive blast mTBI.

And in a cohort of veterans with blast mTBI, blast exposure was found to be associated with an increased burden of frontal cortical MRI-visible perivascular spaces — a “putative neuroimaging marker” of glymphatic perivascular dysfunction.

The earlier Neurology study “showed impairment of biomarkers in the CSF, but the new study showed ‘why’ or ‘how’ these biomarkers are impaired, which is via impairment of the glymphatic clearance process,” Dr. Iliff explained.
 

Veterans Especially Vulnerable

Dr. Peskind, co-director of the VA Northwest Mental Illness Research, Education and Clinical Center, VA Puget Sound Health Care System, noted that while the veterans in the earlier study had at least one TBI, the average number was 20, and it was more common to have more than 50 mTBIs than to have a single one.

“These were highly exposed combat vets,” she said. “And that number doesn’t even account for subconcussive exposure to blasts, which now appear to cause detectable brain damage, even in the absence of a diagnosable TBI.”

The Maine shooter, Mr. Card, had not seen combat and was not assessed for TBI during a psychiatric hospitalization, according to The New York Times.

Dr. Peskind added that this type of blast damage is likely specific to individuals in the military. “It isn’t the sound that causes the damage,” she explained. “It’s the blast wave, the pressure wave, and there aren’t a lot of other occupations that have those types of occupational exposures.”

Dr. Snyder added that the majority of blast TBIs have been studied in military personnel, and she is not aware of studies that have looked at blast injuries in other industries, such as demolition or mining, to see if they have the same type of biologic consequences.

Dr. Snyder hopes that the researchers will follow the participants in the Neurology study and continue looking at specific markers related to Alzheimer’s disease brain changes. What the research so far shows “is that, at an earlier age, we’re starting to see those markers changing, suggesting that the underlying biology in people with mild blast TBI is similar to the underlying biology in Alzheimer’s disease as well.”

Michael Alosco, PhD, associate professor and vice chair of research, department of neurology, Boston University Chobanian & Avedisian School of Medicine, called the issue of blast exposure and TBI “a very complex and nuanced topic,” especially because TBI is “considered a risk factor of Alzheimer’s disease” and “different types of TBIs could trigger distinct pathophysiologic processes; however, the long-term impact of repetitive blast TBIs on neurodegenerative disease changes remains unknown.”

He coauthored an editorial on the earlier Neurology study that noted its limitations, such as a small sample size and lack of consideration of lifestyle and health factors but acknowledged that the “findings provide preliminary evidence that repetitive blast exposures might influence beta-amyloid accumulation.”
 

Clinical Implications

For Dr. Peskind, the “inflection point” was seeing lower CSF Abeta42, about 20 years earlier than ages 60 and 70, which is more typical in cognitively normal community volunteers.

But she described herself as “loath to say that veterans or service members have a 20-year acceleration of risk of Alzheimer’s disease,” adding, “I don’t want to scare the heck out of our service members of veterans.” Although “this is what we fear, we’re not ready to say it for sure yet because we need to do more work. Nevertheless, it does increase the index of suspicion.”

The clinical take-home messages are not unique to service members or veterans or people with a history of head injuries or a genetic predisposition to Alzheimer’s disease, she emphasized. “If anyone of any age or occupation comes in with cognitive issues, such as [impaired] memory or executive function, they deserve a workup for dementing disorders.” Frontotemporal dementia, for example, can present earlier than Alzheimer’s disease typically does.

Common comorbidities with TBI are PTSD and obstructive sleep apnea (OSA), which can also cause cognitive issues and are also risk factors for dementia.

Dr. Iliff agreed. “If you see a veteran with a history of PTSD, a history of blast TBI, and a history of OSA or some combination of those three, I recommend having a higher index of suspicion [for potential dementia] than for an average person without any of these, even at a younger age than one would ordinarily expect.”

Of all of these factors, the only truly directly modifiable one is sleep disruption, including that caused by OSA or sleep disorders related to PTSD, he added. “Epidemiologic data suggest a connection particularly between midlife sleep disruption and the risk of dementia and Alzheimer’s disease, and so it’s worth thinking about sleep as a modifiable risk factor even as early as the 40s and 50s, whether the patient is or isn’t a veteran.”

Dr. Peskind recommended asking patients, “Do they snore? Do they thrash about during sleep? Do they have trauma nightmares? This will inform the type of intervention required.”

Dr. Alosco added that there is no known “safe” threshold of exposure to blasts, and that thresholds are “unclear, particularly at the individual level.” In American football, there is a dose-response relationship between years of play and risk for later-life neurological disorder. “The best way to mitigate risk is to limit cumulative exposure,” he said.

The study by Li and colleagues was funded by grant funding from the Department of Veterans Affairs Rehabilitation Research and Development Service and the University of Washington Friends of Alzheimer’s Research. Other sources of funding to individual researchers are listed in the original paper. The study by Braun and colleagues was supported by the National Heart, Lung and Blood Institute; the Department of Veterans Affairs Rehabilitation Research and Development Service; and the National Institute on Aging. The white paper included studies that received funding from numerous sources, including the National Institutes of Health and the DOD. Dr. Iliff serves as the chair of the Scientific Advisory Board for Applied Cognition Inc., from which he receives compensation and in which he holds an equity stake. In the last year, he served as a paid consultant to Gryphon Biosciences. Dr. Peskind has served as a paid consultant to the companies Genentech, Roche, and Alpha Cognition. Dr. Alosco was supported by grant funding from the NIH; he received research support from Rainwater Charitable Foundation Inc., and Life Molecular Imaging Inc.; he has received a single honorarium from the Michael J. Fox Foundation for services unrelated to this editorial; and he received royalties from Oxford University Press Inc. The other authors’ disclosures are listed in the original papers.
 

A version of this article appeared on Medscape.com.

In October 2023, Robert Card — a grenade instructor in the Army Reserve — shot and killed 18 people in Maine, before turning the gun on himself. As reported by The New York Times, his family said that he had become increasingly erratic and violent during the months before the rampage.

A postmortem conducted by the Chronic Traumatic Encephalopathy (CTE) Center at Boston University found “significant evidence of traumatic brain injuries” [TBIs] and “significant degeneration, axonal and myelin loss, inflammation, and small blood vessel injury” in the white matter, the center’s director, Ann McKee, MD, said in a press release. “These findings align with our previous studies on the effects of blast injury in humans and experimental models.”

Members of the military, such as Mr. Card, are exposed to blasts from repeated firing of heavy weapons not only during combat but also during training.

New data suggest that repeated blast exposure may impair the brain’s waste clearance system, leading to biomarker changes indicative of preclinical Alzheimer’s disease 20 years earlier than typical. A higher index of suspicion for dementia or Alzheimer’s disease may be warranted in patients with a history of blast exposure or subconcussive brain injury who present with cognitive issues, according to experts interviewed.

In 2022, the US Department of Defense (DOD) launched its Warfighter Brain Health Initiative with the aim of “optimizing service member brain health and countering traumatic brain injuries.”

In April 2024, the Blast Overpressure Safety Act was introduced in the Senate to require the DOD to enact better blast screening, tracking, prevention, and treatment. The DOD initiated 26 blast overpressure studies.

Heather Snyder, PhD, Alzheimer’s Association vice president of Medical and Scientific Relations, said that an important component of that research involves “the need to study the difference between TBI-caused dementia and dementia caused independently” and “the need to study biomarkers to better understand the long-term consequences of TBI.”
 

What Is the Underlying Biology?

Dr. Snyder was the lead author of a white paper produced by the Alzheimer’s Association in 2018 on military-related risk factors for Alzheimer’s disease and related dementias. “There is a lot of work trying to understand the effect of pure blast waves on the brain, as opposed to the actual impact of the injury,” she said.

The white paper speculated that blast exposure may be analogous to subconcussive brain injury in athletes where there are no obvious immediate clinical symptoms or neurological dysfunction but which can cause cumulative injury and functional impairment over time.

“We are also trying to understand the underlying biology around brain changes, such as accumulation of tau and amyloid and other specific markers related to brain changes in Alzheimer’s disease,” said Dr. Snyder, chair of the Peer Reviewed Alzheimer’s Research Program Programmatic Panel for Alzheimer’s Disease/Alzheimer’s Disease and Related Dementias and TBI.
 

Common Biomarker Signatures

A recent study in Neurology comparing 51 veterans with mild TBI (mTBI) with 85 veterans and civilians with no lifetime history of TBI is among the first to explore these biomarker changes in human beings.

“Our findings suggest that chronic neuropathologic processes associated with blast mTBI share properties in common with pathogenic processes that are precursors to Alzheimer’s disease onset,” said coauthor Elaine R. Peskind, MD, professor of psychiatry and behavioral sciences, University of Washington, Seattle.

The largely male participants were a mean age of 34 years and underwent standardized clinical and neuropsychological testing as well as lumbar puncture to collect cerebrospinal fluid (CSF). The mTBI group had experienced at least one war zone blast or combined blast/impact that met criteria for mTBI, but 91% had more than one blast mTBI, and the study took place over 13 years.

The researchers found that the mTBI group “had biomarker signatures in common with the earliest stages of Alzheimer’s disease,” said Dr. Peskind.

For example, at age 50, they had lower mean levels of CSF amyloid beta 42 (Abeta42), the earliest marker of brain parenchymal Abeta deposition, compared with the control group (154 pg/mL and 1864 pg/mL lower, respectively).

High CSF phosphorylated tau181 (p-tau181) and total tau are established biomarkers for Alzheimer’s disease. However, levels of these biomarkers remained “relatively constant with age” in participants with mTBI but were higher in older ages for the non-TBI group.

The mTBI group also showed worse cognitive performance at older ages (P < .08). Poorer verbal memory and verbal fluency performance were associated with lower CSF Abeta42 in older participants (P ≤ .05).

In Alzheimer’s disease, a reduction in CSF Abeta42 may occur up to 20 years before the onset of clinical symptoms, according to Dr. Peskind. “But what we don’t know from this study is what this means, as total tau protein and p-tau181 in the CSF were also low, which isn’t entirely typical in the picture of preclinical Alzheimer’s disease,” she said. However, changes in total tau and p-tau181 lag behind changes in Abeta42.
 

Is Impaired Clearance the Culprit?

Coauthor Jeffrey Iliff, PhD, professor, University of Washington Department of Psychiatry and Behavioral Sciences and University of Washington Department of Neurology, Seattle, elaborated.

“In the setting of Alzheimer’s disease, a signature of the disease is reduced CSF Abeta42, which is thought to reflect that much of the amyloid gets ‘stuck’ in the brain in the form of amyloid plaques,” he said. “There are usually higher levels of phosphorylated tau and total tau, which are thought to reflect the presence of tau tangles and degeneration of neurons in the brain. But in this study, all of those were lowered, which is not exactly an Alzheimer’s disease profile.”

Dr. Iliff, associate director for research, VA Northwest Mental Illness Research, Education, and Clinical Center at VA Puget Sound Health Care System, Seattle, suggested that the culprit may be impairment in the brain’s glymphatic system. “Recently described biological research supports [the concept of] clearance of waste out of the brain during sleep via the glymphatic system, with amyloid and tau being cleared from the brain interstitium during sleep.”

A recent hypothesis is that blast TBI impairs that process. “This is why we see less of those proteins in the CSF. They’re not being cleared, which might contribute downstream to the clumping up of protein in the brain,” he suggested.

The evidence base corroborating that hypothesis is in its infancy; however, new research conducted by Dr. Iliff and his colleagues sheds light on this potential mechanism.

In blast TBI, energy from the explosion and resulting overpressure wave are “transmitted through the brain, which causes tissues of different densities — such as gray and white matter — to accelerate at different rates,” according to Dr. Iliff. This results in the shearing and stretching of brain tissue, leading to a “diffuse pattern of tissue damage.”

It is known that blast TBI has clinical overlap and associations with posttraumatic stress disorder (PTSD), depression, and persistent neurobehavioral symptoms; that veterans with a history of TBI are more than twice as likely to die by suicide than veterans with no TBI history; and that TBI may increase the risk for Alzheimer’s disease and related dementing disorders, as well as CTE.

The missing link may be the glymphatic system — a “brain-wide network of perivascular pathways, along which CSF and interstitial fluid (ISF) exchange, supporting the clearance of interstitial solutes, including amyloid-beta.”

Dr. Iliff and his group previously found that glymphatic function is “markedly and chronically impaired” following impact TBI in mice and that this impairment is associated with the mislocalization of astroglial aquaporin 4 (AQP4), a water channel that lines perivascular spaces and plays a role in healthy glymphatic exchange.

In their new study, the researchers examined both the expression and the localization of AQP4 in the human postmortem frontal cortex and found “distinct laminar differences” in AQP4 expression following blast exposure. They observed similar changes as well as impairment of glymphatic function, which emerged 28 days following blast injury in a mouse model of repetitive blast mTBI.

And in a cohort of veterans with blast mTBI, blast exposure was found to be associated with an increased burden of frontal cortical MRI-visible perivascular spaces — a “putative neuroimaging marker” of glymphatic perivascular dysfunction.

The earlier Neurology study “showed impairment of biomarkers in the CSF, but the new study showed ‘why’ or ‘how’ these biomarkers are impaired, which is via impairment of the glymphatic clearance process,” Dr. Iliff explained.
 

Veterans Especially Vulnerable

Dr. Peskind, co-director of the VA Northwest Mental Illness Research, Education and Clinical Center, VA Puget Sound Health Care System, noted that while the veterans in the earlier study had at least one TBI, the average number was 20, and it was more common to have more than 50 mTBIs than to have a single one.

“These were highly exposed combat vets,” she said. “And that number doesn’t even account for subconcussive exposure to blasts, which now appear to cause detectable brain damage, even in the absence of a diagnosable TBI.”

The Maine shooter, Mr. Card, had not seen combat and was not assessed for TBI during a psychiatric hospitalization, according to The New York Times.

Dr. Peskind added that this type of blast damage is likely specific to individuals in the military. “It isn’t the sound that causes the damage,” she explained. “It’s the blast wave, the pressure wave, and there aren’t a lot of other occupations that have those types of occupational exposures.”

Dr. Snyder added that the majority of blast TBIs have been studied in military personnel, and she is not aware of studies that have looked at blast injuries in other industries, such as demolition or mining, to see if they have the same type of biologic consequences.

Dr. Snyder hopes that the researchers will follow the participants in the Neurology study and continue looking at specific markers related to Alzheimer’s disease brain changes. What the research so far shows “is that, at an earlier age, we’re starting to see those markers changing, suggesting that the underlying biology in people with mild blast TBI is similar to the underlying biology in Alzheimer’s disease as well.”

Michael Alosco, PhD, associate professor and vice chair of research, department of neurology, Boston University Chobanian & Avedisian School of Medicine, called the issue of blast exposure and TBI “a very complex and nuanced topic,” especially because TBI is “considered a risk factor of Alzheimer’s disease” and “different types of TBIs could trigger distinct pathophysiologic processes; however, the long-term impact of repetitive blast TBIs on neurodegenerative disease changes remains unknown.”

He coauthored an editorial on the earlier Neurology study that noted its limitations, such as a small sample size and lack of consideration of lifestyle and health factors but acknowledged that the “findings provide preliminary evidence that repetitive blast exposures might influence beta-amyloid accumulation.”
 

Clinical Implications

For Dr. Peskind, the “inflection point” was seeing lower CSF Abeta42, about 20 years earlier than ages 60 and 70, which is more typical in cognitively normal community volunteers.

But she described herself as “loath to say that veterans or service members have a 20-year acceleration of risk of Alzheimer’s disease,” adding, “I don’t want to scare the heck out of our service members of veterans.” Although “this is what we fear, we’re not ready to say it for sure yet because we need to do more work. Nevertheless, it does increase the index of suspicion.”

The clinical take-home messages are not unique to service members or veterans or people with a history of head injuries or a genetic predisposition to Alzheimer’s disease, she emphasized. “If anyone of any age or occupation comes in with cognitive issues, such as [impaired] memory or executive function, they deserve a workup for dementing disorders.” Frontotemporal dementia, for example, can present earlier than Alzheimer’s disease typically does.

Common comorbidities with TBI are PTSD and obstructive sleep apnea (OSA), which can also cause cognitive issues and are also risk factors for dementia.

Dr. Iliff agreed. “If you see a veteran with a history of PTSD, a history of blast TBI, and a history of OSA or some combination of those three, I recommend having a higher index of suspicion [for potential dementia] than for an average person without any of these, even at a younger age than one would ordinarily expect.”

Of all of these factors, the only truly directly modifiable one is sleep disruption, including that caused by OSA or sleep disorders related to PTSD, he added. “Epidemiologic data suggest a connection particularly between midlife sleep disruption and the risk of dementia and Alzheimer’s disease, and so it’s worth thinking about sleep as a modifiable risk factor even as early as the 40s and 50s, whether the patient is or isn’t a veteran.”

Dr. Peskind recommended asking patients, “Do they snore? Do they thrash about during sleep? Do they have trauma nightmares? This will inform the type of intervention required.”

Dr. Alosco added that there is no known “safe” threshold of exposure to blasts, and that thresholds are “unclear, particularly at the individual level.” In American football, there is a dose-response relationship between years of play and risk for later-life neurological disorder. “The best way to mitigate risk is to limit cumulative exposure,” he said.

The study by Li and colleagues was funded by grant funding from the Department of Veterans Affairs Rehabilitation Research and Development Service and the University of Washington Friends of Alzheimer’s Research. Other sources of funding to individual researchers are listed in the original paper. The study by Braun and colleagues was supported by the National Heart, Lung and Blood Institute; the Department of Veterans Affairs Rehabilitation Research and Development Service; and the National Institute on Aging. The white paper included studies that received funding from numerous sources, including the National Institutes of Health and the DOD. Dr. Iliff serves as the chair of the Scientific Advisory Board for Applied Cognition Inc., from which he receives compensation and in which he holds an equity stake. In the last year, he served as a paid consultant to Gryphon Biosciences. Dr. Peskind has served as a paid consultant to the companies Genentech, Roche, and Alpha Cognition. Dr. Alosco was supported by grant funding from the NIH; he received research support from Rainwater Charitable Foundation Inc., and Life Molecular Imaging Inc.; he has received a single honorarium from the Michael J. Fox Foundation for services unrelated to this editorial; and he received royalties from Oxford University Press Inc. The other authors’ disclosures are listed in the original papers.
 

A version of this article appeared on Medscape.com.

SAN DIEGO — In a bid to address the severe shortage of headache neurologists across the United States, the American Headache Society (AHS) has developed a program aimed at primary care physicians (PCPs) to help address the unmet demand for headache treatment and management.

It is estimated that about 4 million PCP office visits annually are headache related, and that 52.8% of all migraine encounters occur in primary care settings.

However, PCPs aren’t always adequately trained in headache management and referral times to specialist care can be lengthy.

Data published in Headache show only 564 accredited headache specialists practice in the United States, but at least 3700 headache specialists are needed to treat those affected by migraine, with even more needed to address other disabling headache types such as tension-type headache and cluster headache. To keep up with population growth, it is estimated that the United States will require 4500 headache specialists by 2040.
 

First Contact

To tackle this specialist shortfall, the AHS developed the First Contact program with the aim of improving headache education in primary care and help alleviate at least some of the demand for specialist care.

The national program was rolled out in 2020 and 2021. The educational symposia were delivered to PCPs at multiple locations across the country. The initiative also included a comprehensive website with numerous support resources.

After participating in the initiative, attendees were surveyed about the value of the program, and the results were subsequently analyzed and presented at the annual meeting of the American Headache Society.

The analysis included 636 survey respondents, a 38% response rate. Almost all participants (96%) were MDs and DOs. The remainder included nurse practitioners, physician assistants, and dentists.

About 85.6% of respondents reported being completely or very confident in their ability to recognize and accurately diagnose headache disorders, and 81.3% said they were completely or very confident in their ability to create tailored treatment plans.

Just over 90% of participants reported they would implement practice changes as a result of the program. The most commonly cited change was the use of diagnostic tools such as the three-question Migraine ID screener, followed closely by consideration of prescribing triptans and reducing the use of unnecessary neuroimaging.

“Overall, there was a positive response to this type of educational programming and interest in ongoing education in addressing headache disorders with both pharmaceutical and non-pharmaceutical treatment options,” said Nisha Malhotra, MD, a resident at New York University (NYU) Langone Health, New York City, who presented the findings at the conference.

The fact that so many general practitioners were keen to use this easy-to-use screen [Migraine ID screener], which can pick up about 90% of people with migraine, is “great,” said study investigator Mia Minen, MD, associate professor and chief of headache research at NYU Langone Health. “I’m pleased primary care providers said they were considering implementing this simple tool.”

However, respondents also cited barriers to change. These included cost constraints (48.9%), insurance reimbursement issues (48.6%), and lack of time (45.3%). Dr. Malhotra noted these concerns are primarily related to workflow rather than knowledge gaps or lack of training.

“This is exciting in that there doesn’t seem to be an issue with education primarily but rather with the logistical issues that exist in the workflow in a primary care setting,” said Dr. Malhotra.

Participants also noted the need for other improvements. For example, they expressed interest in differentiating migraine from other headache types and having a better understanding of how and when to refer to specialists, said Dr. Malhotra.

These practitioners also want to know more about treatment options beyond first-line medications. “They were interested in understanding more advanced medication treatment options beyond just the typical triptan,” said Dr. Malhotra.

In addition, they want to become more skilled in non-pharmaceutical options such as occipital nerve blocks and in massage, acupuncture, and other complementary forms of migraine management, she said.

The study may be vulnerable to sampling bias as survey participants had just attended an educational symposium on headaches. “They were already, to some degree, interested in improving their knowledge on headache,” said Dr. Malhotra.

Another study limitation was that researchers didn’t conduct a pre-survey analysis to determine changes as a result of the symposia. And as the survey was conducted so close to the symposium, “it’s difficult to draw conclusions on the long-term effects,” she added.

“That being said, First Contact is one of the first national initiatives for primary care education, and thus far, it has been very well received.”

The next step is to continue expanding the program and to create a First Contact for women and First Contact for pediatrics, said Dr. Minen.
 

Improved Diagnosis, Better Care

Commenting on the initiative, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, who co-chaired the session where the survey results were presented, said it helps address the supply-demand imbalance in headache healthcare.

“Many, many people have headache disorders, and very few people are technically headache specialists, so we have to rely on our colleagues in primary care to help address the great need that’s out there for patients with headache disorders.”

Too many patients don’t get a proper diagnosis or appropriate treatment, said Dr. VanderPluym, so as time passes, “diseases can become more chronic and more refractory, and it affects people’s quality of life and productivity.”

The First Contact program, she said, helps increase providers’ comfort and confidence that they are providing the best patient care possible and lead to a reduction in the need for specialist referrals.

Dr. Minen serves on the First Contact advisory board.
 

A version of this article appeared on Medscape.com.

SAN DIEGO — In a bid to address the severe shortage of headache neurologists across the United States, the American Headache Society (AHS) has developed a program aimed at primary care physicians (PCPs) to help address the unmet demand for headache treatment and management.

It is estimated that about 4 million PCP office visits annually are headache related, and that 52.8% of all migraine encounters occur in primary care settings.

However, PCPs aren’t always adequately trained in headache management and referral times to specialist care can be lengthy.

Data published in Headache show only 564 accredited headache specialists practice in the United States, but at least 3700 headache specialists are needed to treat those affected by migraine, with even more needed to address other disabling headache types such as tension-type headache and cluster headache. To keep up with population growth, it is estimated that the United States will require 4500 headache specialists by 2040.
 

First Contact

To tackle this specialist shortfall, the AHS developed the First Contact program with the aim of improving headache education in primary care and help alleviate at least some of the demand for specialist care.

The national program was rolled out in 2020 and 2021. The educational symposia were delivered to PCPs at multiple locations across the country. The initiative also included a comprehensive website with numerous support resources.

After participating in the initiative, attendees were surveyed about the value of the program, and the results were subsequently analyzed and presented at the annual meeting of the American Headache Society.

The analysis included 636 survey respondents, a 38% response rate. Almost all participants (96%) were MDs and DOs. The remainder included nurse practitioners, physician assistants, and dentists.

About 85.6% of respondents reported being completely or very confident in their ability to recognize and accurately diagnose headache disorders, and 81.3% said they were completely or very confident in their ability to create tailored treatment plans.

Just over 90% of participants reported they would implement practice changes as a result of the program. The most commonly cited change was the use of diagnostic tools such as the three-question Migraine ID screener, followed closely by consideration of prescribing triptans and reducing the use of unnecessary neuroimaging.

“Overall, there was a positive response to this type of educational programming and interest in ongoing education in addressing headache disorders with both pharmaceutical and non-pharmaceutical treatment options,” said Nisha Malhotra, MD, a resident at New York University (NYU) Langone Health, New York City, who presented the findings at the conference.

The fact that so many general practitioners were keen to use this easy-to-use screen [Migraine ID screener], which can pick up about 90% of people with migraine, is “great,” said study investigator Mia Minen, MD, associate professor and chief of headache research at NYU Langone Health. “I’m pleased primary care providers said they were considering implementing this simple tool.”

However, respondents also cited barriers to change. These included cost constraints (48.9%), insurance reimbursement issues (48.6%), and lack of time (45.3%). Dr. Malhotra noted these concerns are primarily related to workflow rather than knowledge gaps or lack of training.

“This is exciting in that there doesn’t seem to be an issue with education primarily but rather with the logistical issues that exist in the workflow in a primary care setting,” said Dr. Malhotra.

Participants also noted the need for other improvements. For example, they expressed interest in differentiating migraine from other headache types and having a better understanding of how and when to refer to specialists, said Dr. Malhotra.

These practitioners also want to know more about treatment options beyond first-line medications. “They were interested in understanding more advanced medication treatment options beyond just the typical triptan,” said Dr. Malhotra.

In addition, they want to become more skilled in non-pharmaceutical options such as occipital nerve blocks and in massage, acupuncture, and other complementary forms of migraine management, she said.

The study may be vulnerable to sampling bias as survey participants had just attended an educational symposium on headaches. “They were already, to some degree, interested in improving their knowledge on headache,” said Dr. Malhotra.

Another study limitation was that researchers didn’t conduct a pre-survey analysis to determine changes as a result of the symposia. And as the survey was conducted so close to the symposium, “it’s difficult to draw conclusions on the long-term effects,” she added.

“That being said, First Contact is one of the first national initiatives for primary care education, and thus far, it has been very well received.”

The next step is to continue expanding the program and to create a First Contact for women and First Contact for pediatrics, said Dr. Minen.
 

Improved Diagnosis, Better Care

Commenting on the initiative, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, who co-chaired the session where the survey results were presented, said it helps address the supply-demand imbalance in headache healthcare.

“Many, many people have headache disorders, and very few people are technically headache specialists, so we have to rely on our colleagues in primary care to help address the great need that’s out there for patients with headache disorders.”

Too many patients don’t get a proper diagnosis or appropriate treatment, said Dr. VanderPluym, so as time passes, “diseases can become more chronic and more refractory, and it affects people’s quality of life and productivity.”

The First Contact program, she said, helps increase providers’ comfort and confidence that they are providing the best patient care possible and lead to a reduction in the need for specialist referrals.

Dr. Minen serves on the First Contact advisory board.
 

A version of this article appeared on Medscape.com.

SAN DIEGO — In a bid to address the severe shortage of headache neurologists across the United States, the American Headache Society (AHS) has developed a program aimed at primary care physicians (PCPs) to help address the unmet demand for headache treatment and management.

It is estimated that about 4 million PCP office visits annually are headache related, and that 52.8% of all migraine encounters occur in primary care settings.

However, PCPs aren’t always adequately trained in headache management and referral times to specialist care can be lengthy.

Data published in Headache show only 564 accredited headache specialists practice in the United States, but at least 3700 headache specialists are needed to treat those affected by migraine, with even more needed to address other disabling headache types such as tension-type headache and cluster headache. To keep up with population growth, it is estimated that the United States will require 4500 headache specialists by 2040.
 

First Contact

To tackle this specialist shortfall, the AHS developed the First Contact program with the aim of improving headache education in primary care and help alleviate at least some of the demand for specialist care.

The national program was rolled out in 2020 and 2021. The educational symposia were delivered to PCPs at multiple locations across the country. The initiative also included a comprehensive website with numerous support resources.

After participating in the initiative, attendees were surveyed about the value of the program, and the results were subsequently analyzed and presented at the annual meeting of the American Headache Society.

The analysis included 636 survey respondents, a 38% response rate. Almost all participants (96%) were MDs and DOs. The remainder included nurse practitioners, physician assistants, and dentists.

About 85.6% of respondents reported being completely or very confident in their ability to recognize and accurately diagnose headache disorders, and 81.3% said they were completely or very confident in their ability to create tailored treatment plans.

Just over 90% of participants reported they would implement practice changes as a result of the program. The most commonly cited change was the use of diagnostic tools such as the three-question Migraine ID screener, followed closely by consideration of prescribing triptans and reducing the use of unnecessary neuroimaging.

“Overall, there was a positive response to this type of educational programming and interest in ongoing education in addressing headache disorders with both pharmaceutical and non-pharmaceutical treatment options,” said Nisha Malhotra, MD, a resident at New York University (NYU) Langone Health, New York City, who presented the findings at the conference.

The fact that so many general practitioners were keen to use this easy-to-use screen [Migraine ID screener], which can pick up about 90% of people with migraine, is “great,” said study investigator Mia Minen, MD, associate professor and chief of headache research at NYU Langone Health. “I’m pleased primary care providers said they were considering implementing this simple tool.”

However, respondents also cited barriers to change. These included cost constraints (48.9%), insurance reimbursement issues (48.6%), and lack of time (45.3%). Dr. Malhotra noted these concerns are primarily related to workflow rather than knowledge gaps or lack of training.

“This is exciting in that there doesn’t seem to be an issue with education primarily but rather with the logistical issues that exist in the workflow in a primary care setting,” said Dr. Malhotra.

Participants also noted the need for other improvements. For example, they expressed interest in differentiating migraine from other headache types and having a better understanding of how and when to refer to specialists, said Dr. Malhotra.

These practitioners also want to know more about treatment options beyond first-line medications. “They were interested in understanding more advanced medication treatment options beyond just the typical triptan,” said Dr. Malhotra.

In addition, they want to become more skilled in non-pharmaceutical options such as occipital nerve blocks and in massage, acupuncture, and other complementary forms of migraine management, she said.

The study may be vulnerable to sampling bias as survey participants had just attended an educational symposium on headaches. “They were already, to some degree, interested in improving their knowledge on headache,” said Dr. Malhotra.

Another study limitation was that researchers didn’t conduct a pre-survey analysis to determine changes as a result of the symposia. And as the survey was conducted so close to the symposium, “it’s difficult to draw conclusions on the long-term effects,” she added.

“That being said, First Contact is one of the first national initiatives for primary care education, and thus far, it has been very well received.”

The next step is to continue expanding the program and to create a First Contact for women and First Contact for pediatrics, said Dr. Minen.
 

Improved Diagnosis, Better Care

Commenting on the initiative, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, who co-chaired the session where the survey results were presented, said it helps address the supply-demand imbalance in headache healthcare.

“Many, many people have headache disorders, and very few people are technically headache specialists, so we have to rely on our colleagues in primary care to help address the great need that’s out there for patients with headache disorders.”

Too many patients don’t get a proper diagnosis or appropriate treatment, said Dr. VanderPluym, so as time passes, “diseases can become more chronic and more refractory, and it affects people’s quality of life and productivity.”

The First Contact program, she said, helps increase providers’ comfort and confidence that they are providing the best patient care possible and lead to a reduction in the need for specialist referrals.

Dr. Minen serves on the First Contact advisory board.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Poor vision and contrast sensitivity at baseline increase the likelihood of incident dementia in older adults; a decline in contrast sensitivity over time also correlates with the risk of developing dementia.

METHODOLOGY:

• Researchers conducted a longitudinal study to analyze the association of visual function with the risk for dementia in 2159 men and women (mean age, 77.9 years; 54% women) included from the National Health and Aging Trends Study between 2021 and 2022.
• All participants were free from dementia at baseline and underwent visual assessment while wearing their usual glasses or contact lenses.
• Distance and near visual acuity were measured as the log minimum angle of resolution (logMAR) units where higher values indicated worse visual acuity; contrast sensitivity was measured as the log contrast sensitivity (logCS) units where lower values represented worse outcomes.
• Dementia status was determined by a medical diagnosis, a dementia score of 2 or more, or poor performance on cognitive testing.

TAKEAWAY:

• Over the 1-year follow-up period, 192 adults (6.6%) developed dementia.
• Worsening of distant and near vision by 0.1 logMAR increased the risk for dementia by 8% (P = .01) and 7% (P = .02), respectively.
• Each 0.1 logCS decline in baseline contrast sensitivity increased the risk for dementia by 9% (P = .003).
• A yearly decline in contrast sensitivity by 0.1 logCS increased the likelihood of dementia by 14% (P = .007).
• Changes in distant and near vision over time did not show a significant association with risk for dementia (P = .58 and P = .79, respectively).

IN PRACTICE:

“Visual function, especially contrast sensitivity, might be a risk factor for developing dementia,” the authors wrote. “Early vision screening may help identify adults at higher risk of dementia, allowing for timely interventions.”

SOURCE:

The study was led by Louay Almidani, MD, MSc, of the Wilmer Eye Institute at the Johns Hopkins University School of Medicine, in Baltimore, and was published online in the American Journal of Ophthalmology.

LIMITATIONS:

The study had a limited follow-up period of 1 year and may not have captured the long-term association between visual impairment and the risk for dementia. Moreover, the researchers did not consider other visual function measures such as depth perception and visual field, which might have affected the results.

DISCLOSURES:

The study did not have any funding source. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Poor vision and contrast sensitivity at baseline increase the likelihood of incident dementia in older adults; a decline in contrast sensitivity over time also correlates with the risk of developing dementia.

METHODOLOGY:

• Researchers conducted a longitudinal study to analyze the association of visual function with the risk for dementia in 2159 men and women (mean age, 77.9 years; 54% women) included from the National Health and Aging Trends Study between 2021 and 2022.
• All participants were free from dementia at baseline and underwent visual assessment while wearing their usual glasses or contact lenses.
• Distance and near visual acuity were measured as the log minimum angle of resolution (logMAR) units where higher values indicated worse visual acuity; contrast sensitivity was measured as the log contrast sensitivity (logCS) units where lower values represented worse outcomes.
• Dementia status was determined by a medical diagnosis, a dementia score of 2 or more, or poor performance on cognitive testing.

TAKEAWAY:

• Over the 1-year follow-up period, 192 adults (6.6%) developed dementia.
• Worsening of distant and near vision by 0.1 logMAR increased the risk for dementia by 8% (P = .01) and 7% (P = .02), respectively.
• Each 0.1 logCS decline in baseline contrast sensitivity increased the risk for dementia by 9% (P = .003).
• A yearly decline in contrast sensitivity by 0.1 logCS increased the likelihood of dementia by 14% (P = .007).
• Changes in distant and near vision over time did not show a significant association with risk for dementia (P = .58 and P = .79, respectively).

IN PRACTICE:

“Visual function, especially contrast sensitivity, might be a risk factor for developing dementia,” the authors wrote. “Early vision screening may help identify adults at higher risk of dementia, allowing for timely interventions.”

SOURCE:

The study was led by Louay Almidani, MD, MSc, of the Wilmer Eye Institute at the Johns Hopkins University School of Medicine, in Baltimore, and was published online in the American Journal of Ophthalmology.

LIMITATIONS:

The study had a limited follow-up period of 1 year and may not have captured the long-term association between visual impairment and the risk for dementia. Moreover, the researchers did not consider other visual function measures such as depth perception and visual field, which might have affected the results.

DISCLOSURES:

The study did not have any funding source. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Poor vision and contrast sensitivity at baseline increase the likelihood of incident dementia in older adults; a decline in contrast sensitivity over time also correlates with the risk of developing dementia.

METHODOLOGY:

• Researchers conducted a longitudinal study to analyze the association of visual function with the risk for dementia in 2159 men and women (mean age, 77.9 years; 54% women) included from the National Health and Aging Trends Study between 2021 and 2022.
• All participants were free from dementia at baseline and underwent visual assessment while wearing their usual glasses or contact lenses.
• Distance and near visual acuity were measured as the log minimum angle of resolution (logMAR) units where higher values indicated worse visual acuity; contrast sensitivity was measured as the log contrast sensitivity (logCS) units where lower values represented worse outcomes.
• Dementia status was determined by a medical diagnosis, a dementia score of 2 or more, or poor performance on cognitive testing.

TAKEAWAY:

• Over the 1-year follow-up period, 192 adults (6.6%) developed dementia.
• Worsening of distant and near vision by 0.1 logMAR increased the risk for dementia by 8% (P = .01) and 7% (P = .02), respectively.
• Each 0.1 logCS decline in baseline contrast sensitivity increased the risk for dementia by 9% (P = .003).
• A yearly decline in contrast sensitivity by 0.1 logCS increased the likelihood of dementia by 14% (P = .007).
• Changes in distant and near vision over time did not show a significant association with risk for dementia (P = .58 and P = .79, respectively).

IN PRACTICE:

“Visual function, especially contrast sensitivity, might be a risk factor for developing dementia,” the authors wrote. “Early vision screening may help identify adults at higher risk of dementia, allowing for timely interventions.”

SOURCE:

The study was led by Louay Almidani, MD, MSc, of the Wilmer Eye Institute at the Johns Hopkins University School of Medicine, in Baltimore, and was published online in the American Journal of Ophthalmology.

LIMITATIONS:

The study had a limited follow-up period of 1 year and may not have captured the long-term association between visual impairment and the risk for dementia. Moreover, the researchers did not consider other visual function measures such as depth perception and visual field, which might have affected the results.

DISCLOSURES:

The study did not have any funding source. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.