Neuropathologic Correlates of Seizures in Patients With Alzheimer Disease and Dementia With Lewy Bodies

BACKGROUND AND OBJECTIVES: Seizures are a recognized comorbidity in dementia, with varying prevalence across Alzheimer disease (AD) and dementia with Lewy bodies (DLBs). Although previous studies have demonstrated an increased seizure risk in AD, the neuropathologic substrates underlying seizure susceptibility-particularly across dementia subtypes-remain incompletely understood. We aimed to identify distinct clinicopathologic correlates of clinically active seizures in AD and DLB using a large autopsy-confirmed cohort. METHODS: We conducted a retrospective cohort study using data from the National Alzheimer's Coordinating Center (2005-December 2022). Autopsy-confirmed AD and DLB cases were included. Individuals with a history of stroke or traumatic brain injury were excluded. The primary outcome was clinically active seizures, defined as seizures occurring within 3 years before or after the diagnosis of dementia. Neuropathologic exposures included Braak stage, cerebral amyloid angiopathy (CAA), frontotemporal lobar degeneration, and vascular pathologies. Multivariable logistic regression models were used to examine associations between pathologic features and seizure occurrence, adjusting for relevant demographic covariates. RESULTS: = 0.015). DISCUSSION: In this autopsy-confirmed cohort, seizure susceptibility was associated with advanced tau pathology and CAA in AD. In DLB, exploratory analyses suggested a possible association between vascular pathology and seizures; however, these findings should be interpreted cautiously. Overall, the results support potentially distinct pathologic contributions to seizure susceptibility across dementia subtypes. Limitations include the use of advanced-stage pathologic samples, which may limit generalizability to earlier disease stages.