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Importance: The risk of developing epilepsy substantially increases after the age of 60 years (late-onset epilepsy LOE), particularly in people with cognitive decline (PWCD ie, dementia and/or mild cognitive impairment). Epilepsy is associated with worse cognitive and mortality outcomes in PWCD. Identifying PWCD at risk for developing LOE can facilitate early screening and treatment of epilepsy. Objective: To investigate factors associated with LOE in PWCD. Design, Setting, and Participants: This longitudinal, multicenter study is based on participants from 39 US Alzheimer's Disease Research Centers from September 2005 through December 2021. Of 44 713 participants, 25 119 PWCD were identified. Of these, 14 685 were included who did not have epilepsy at enrollment, had 2 or more visits, and were 60 years or older at the most recent follow-up. Exposure: The association between various factors and LOE development in PWCD was investigated. Main Outcomes and Measures: The primary outcome was LOE, defined as seizures starting at or after 60 years of age. Those who did not develop LOE but were 60 years or older at follow-up served as controls. A multivariable Cox regression analysis assessed the association between various factors and LOE. Independent variables included age, sex, and socioeconomic factors (education, race, ethnicity), cardiovascular risks (hypertension, diabetes, hyperlipidemia), cerebrovascular disease (stroke or history of transient ischemic attack TIA), other neurologic comorbidities (Parkinson disease PD, traumatic brain injury), cognition (age at dementia onset, dementia severity, type of dementia Alzheimer disease (AD) vs non-AD), genetics (apolipoprotein E4 APOE4 status), lifestyle (alcohol misuse, smoking), and depression. Results: Of the 14 685 participants (7355 female 50% and 7330 male 50%; mean SD age, 73.8 8.5 years) who met the inclusion criteria, 221 participants (1.5%) developed LOE during follow-up. After adjusting for demographics, cardiovascular risks, neurologic comorbidities, genetics, cognitive factors, and depression, the following were associated with a higher risk of developing LOE: APOE4 allele (adjusted hazard ratio aHR, 1.39; 95% CI, 1.04-1.86; P = .03), dementia onset before age 60 years (aHR, 2.46; 95% CI, 1.53-3.95; P < .001), worse cognition (aHR, 2.35; 95% CI, 1.97-2.79; P < .001), AD dementia subtype (aHR, 1.68; 95% CI, 1.13-2.49; P = .01), stroke/TIA (aHR, 2.03; 95% CI, 1.37-3.01; P < .001), and PD (aHR, 2.53; 95% CI, 1.08-5.95; P = .03). In sensitivity analysis, using an alternative LOE definition of epilepsy onset after age 65 years revealed the same factors associated with LOE. Conclusion and Relevance: This study showed that the APOE4 allele, dementia onset before age 60 years, AD dementia subtype, worse cognition, stroke/TIA, and PD are associated with LOE development in PWCD. PWCD with these risk factors may be considered for routine screening with an electroencephalogram for early identification of LOE.
Zawar et al. (Mon,) studied this question.