Seizures in people with dementia (PWD) are linked to faster cognitive decline, but the effects of ongoing seizures on postmortem neuropathological changes remain unclear.

The study objective was to explore the impact of active versus remote seizures on postmortem findings in PWD, using data from 39 Alzheimer’s disease centers in the US, collected from September 2005 to December 2021.

Participants with all-cause dementia were classified into three groups: active seizures (within the past year), remote seizures (previous but not recent), and no seizures (controls). The differences in baseline demographics, mortality rates, and postmortem findings were analyzed using Pearson’s Chi-squared test, Fisher’s exact test, t-test, and ANOVA.

Among the 10,474 deceased participants, those with active seizures had the highest mortality (active=56%, remote=35%, controls=34%, p<0.001). Autopsies were performed on 6,085 participants (58.1% of the deceased), including 294 with active seizures, 151 with remote seizures, and 5,640 controls. The groups differed by age at death (active=75.8 years, remote=77.9 years, controls=80.8 years, p<0.001) and dementia severity (CDR-Global: active=2.36, remote=1.90, controls=1.69, p<0.001), but had no differences in education, sex, or race. Post hoc analyses revealed that PWD with active seizures had more severe Alzheimer’s disease pathology, including higher Braak stages and denser neocortical neuritic plaques, compared to remote seizure participants and controls. Active seizure participants also showed greater cerebral and hippocampal atrophy and locus coeruleus hypopigmentation. However, lobar atrophy, vascular pathology, and Lewy body pathology were similar across the groups, while frontotemporal degeneration with tau pathology was less common in the active seizure group.

These findings highlight that ongoing seizures are associated with more severe neurodegeneration, emphasizing the importance of aggressive seizure management to mitigate neurodegenerative progression.