Vascular Risk Factors Associated With Late-Onset Epilepsy in Older Adults
Key Clinical Summary
- An individual participant data meta-analysis of 6 US population-based cohorts involving 42,257 older adults found that several vascular risk factors were associated with increased risk of late-onset epilepsy (LOE).
- History of stroke showed the strongest association among the reported vascular risk factors, with nearly twice the hazard of incident LOE (hazard ratio [HR], 1.99; 95% CI, 1.63-2.43).
- Current smoking, hypertension, diabetes, chronic kidney disease, and apolipoprotein E (APOE) ε4 allele status were also associated with increased LOE risk, with generally consistent findings across demographic subgroups.
Several vascular risk factors, including smoking, hypertension, diabetes and prior stroke, were associated with LOE in older adults, according to pooled analysis findings published in JAMA Neurology. The results suggest that LOE, defined as epilepsy beginning at age 65 years or older, may reflect an underlying burden of brain vascular disease.
Study Findings
The researchers conducted a meta-analysis of individual participant data from 6 US population-based cohorts participating in the Epilepsy-Cog Study to identify the vascular risk factors associated with LOE.
The analysis included 42,257 participants with a mean age of 71.4 years. Investigators assessed vascular risk factors using self-reported information, clinical examinations, laboratory measures, and medication use. Associations with incident LOE were evaluated using multivariable Cox proportional hazards models.
Over a mean 9.3 years of follow-up, 1500 participants (3.5%) developed LOE, corresponding to an incidence rate of 3.8 per 1000 person-years. Fully-adjusted models found that risk of LOE was higher with the presence of several vascular factors, including current smoking (HR = 1.39; 95% CI, 1.18-1.64), hypertension (HR = 1.17; 95% CI, 1.04-1.31), diabetes (HR = 1.42; 95% CI, 1.25-1.62), chronic kidney disease (HR = 1.29; 95% CI, 1.13-1.48), and history of stroke (HR = 1.99; 95% CI, 1.63-2.43).
APOE ε4 allele status was also associated with LOE risk. Participants carrying 1 ε4 allele had a 22% higher hazard (HR, 1.22; 95% CI, 1.07-1.39), while those carrying 2 ε4 alleles had an 84% higher hazard (HR, 1.84; 95% CI, 1.36-2.50).
The relationship between vascular risk factors and LOE was similar across age, sex, and race and ethnicity subgroups.
Clinical Implications
The findings highlight associations between vascular health and the development of epilepsy in older adults, suggesting that LOE may reflect an underlying burden of brain vascular disease.
For clinicians caring for older adults, the results identify several vascular conditions and exposures that may warrant further investigation when evaluating LOE risk.
Expert Commentary
“In this pooled cohort study, modifiable vascular risk factors, history of stroke, and APOE ε4 genotype were independently associated with risk for LOE, supporting the hypothesis that LOE reflects underlying vascular burden in the brain,” wrote Hyunmi Choi, MD, MS, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, and study coauthors.
“Future studies should evaluate whether adding LOE as a risk factor provides incremental prognostic information beyond established cardiovascular risk calculators,” they concluded.
