Late-onset epilepsy incidence among adults aged 65 and older is two- to threefold higher than that

Late-onset epilepsy incidence among adults aged 65 and older is two- to threefold higher than that of Parkinson’s disease and approaches the rate of stroke, according to a pooled analysis published on October 19 in JAMA Neurology and reported by Medscape. Researchers combining data from six US population-based cohorts found that smoking, hypertension, diabetes, chronic kidney disease, APOE epsilon 4 alleles, and prior stroke were each independently linked to a higher risk for late-onset epilepsy, indicating the condition may serve as a marker of underlying vascular brain disease.

Vascular Risk Factors Drive Late-Onset Epilepsy Risk

The analysis tracked 42,257 adults with a mean age of 71.4 years who had no history of epilepsy, drawing from cohorts whose primary purposes involved cardiovascular and cerebrovascular health with follow-up data spanning from 1991 to 2024. Among the participants, 56.0% were women, about 26% were non-Hispanic Black, and 10% were Hispanic. A history of stroke nearly doubled the risk for late-onset epilepsy with an adjusted hazard ratio of 1.99. Diabetes, current smoking, chronic kidney disease, and hypertension also showed significant associations, with adjusted hazard ratios ranging from 1.17 to 1.42.

Carrying one or two apolipoprotein E epsilon 4 alleles raised the risk by 22% and 84%, respectively. The variant is strongly tied to Alzheimer’s disease, suggesting it may contribute through Alzheimer-related changes, vascular brain injury, or both. Meanwhile, hypercholesterolemia, body mass index, and a history of myocardial infarction showed no association with late-onset epilepsy after full adjustment. Each 10-mg/dL increase in fasting glucose tied to a 3% higher risk, while glucose- and blood pressure-lowering medications were associated with 75% and 18% higher risks in models that included medication use.

Late-onset epilepsy remains historically underrecognized

Late-onset epilepsy remains historically underrecognized because epilepsy research has primarily focused on younger patients with drug-resistant temporal lobe epilepsy. Lead investigator Hyunmi Choi, an epileptologist in the Department of Neurology at Columbia University Irving Medical Center in New York City, stated that older adults can present with transient alterations in awareness that clinicians may mistakenly attribute to transient ischemic attacks or progressive dementia. Choi emphasized that the medical community’s focus has traditionally centered solely on seizure control rather than recognizing the condition as a signal of underlying vascular burden.

Seizures in older populations frequently differ from the generalized tonic-clonic events clinicians typically expect. Rani A. Sarkis, an epileptologist and behavioral neurologist at Mass General Brigham and associate professor of neurology at Harvard Medical School, noted that patients may experience transient epileptic amnesia, prolonged confusion lasting hours or days, or episodes resembling panic attacks. Sarkis pointed out that many individuals experience these symptoms for a year or two before a major seizure prompts medical attention, meaning diagnosed incidence rates likely underestimate the true frequency of the condition.

Investigators acknowledged several limitations in the pooled analysis

Study investigators acknowledged several limitations in the pooled analysis. Diagnoses relied on Medicare claims rather than clinical confirmation, stroke history was self-reported, and risk factors were assessed only at cohort entry without updates during the follow-up period. Because participants could develop hypertension or diabetes years after entering the cohort without being reclassified, Choi indicated the true associations may actually be stronger than those observed. The absence of brain imaging meant researchers could not separate poststroke epilepsy cases from unexplained ones.

Johan Zelano, a senior physician in neurology at Sahlgrenska University Hospital in Gothenburg, Sweden, who did not participate in the study, described the methodology as very rigorous in resolving whether late-onset seizures and vascular risk factors share a true association. Zelano noted that whether lowering vascular risk actively prevents late-onset epilepsy remains an unanswered question. Sarkis reported that the findings have already altered his clinical practice, prompting him to evaluate and manage broader vascular risks alongside seizure control during patient visits.

Researchers combined data from six US cohorts

What was the primary data source for the analysis?

Researchers combined individual-level data from six US population-based cohorts focused on cardiovascular and cerebrovascular health, with follow-up tracking spanning from 1991 to 2024.

How was epilepsy identified in the cohorts?

In five of the cohorts, epilepsy was identified using validated Medicare claims definitions that combined diagnostic codes with antiseizure medication use, while the sixth cohort relied on medical record review adjudicated by a study neurologist.

Which specific vascular factor link was explored for the first time?

Chronic kidney disease was evaluated as a risk factor for late-onset epilepsy, showing an adjusted hazard ratio of 1.29 in a link not previously explored in this context.

What did researchers conclude about APOE epsilon 4 alleles?

Carrying one or two APOE epsilon 4 alleles was associated with 22% and 84% higher risks for late-onset epilepsy, respectively, pointing to a potential contribution from Alzheimer-related changes, vascular brain injury, or both.