Predictors of Seizure Occurrence After Mild Cognitive Impairment and Alzheimer’s Disease in Older Adults in the Veterans Affairs Healthcare System: A Retrospective Cohort Study

This was a retrospective epidemiological study to identify the predictors of incidence seizures among older adults with all-cause mild cognitive impairment (MCI) and Alzheimer’s disease (AD) receiving care in the Veterans Affairs Healthcare System (VAHS). Veterans aged ≥ 50 years with MCI or AD were identified using pre-specified diagnostic code and clinical note algorithms in VAHS electronic health records, with linkage to Medicare claims where available, during 2016–2023. Seizures were identified using ICD-10-CM codes for convulsions and epilepsy (R56.x and G40.x), excluding codes considered unlikely to represent unprovoked seizures (e.g., G40.5). Individuals with any seizure/epilepsy diagnosis prior to the index MCI/AD date (or matched control date) were excluded. Multivariate Cox proportional hazards models were used to estimate associations but not causal relationships between baseline comorbidities and subsequent seizure risk. A total of 747,475 individuals with AD or MCI and 747,475 age- and sex-matched non-MCI/AD comparators were identified; after excluding those with pre-index seizures, the analytic cohorts included 482,364 MCI, 223,312 AD, and 736,118 comparator veterans. Compared with non-MCI/AD controls, seizure risk was higher in MCI (HR 2.89, 95% CI 2.80–2.99) and AD (HR 3.19, 95% CI 2.99–3.41). In adjusted analyses, seizure risk was higher among black veterans (HR 1.38, 95% CI 1.31–1.46) than white veterans. Comorbidities with the strongest adjusted associations included traumatic brain injury (HR 1.88, 95% CI 1.68–2.10), central nervous system infection (HR 1.88, 95% CI 1.21–2.92), cerebrovascular disease (HR 1.72, 95% CI 1.63–1.81), and hemorrhagic stroke (HR 1.61, 95% CI 1.39–1.86). Much of the excess risk was associated with cerebrovascular and neurologic comorbidity. Our study showed that seizure risk is elevated in MCI and AD, with specific comorbidities associated with risk of seizure occurrence and cognitive decline, suggesting potentially actionable targets for risk stratification and clinical monitoring.