Seizure Activity Correlates with Severe Neuropathology and Mortality in Dementia
Overview
Active seizures in people with dementia (PWD) are linked to earlier death, more severe cognitive decline, and advanced Alzheimer’s disease (AD) pathology at autopsy. Compared to remote or no seizures, active seizures associate with greater neurodegeneration and worse post-mortem ATN (amyloid, tau, neurodegeneration) pathology.
Background
Seizures are common in PWD and contribute to accelerated cognitive decline and increased mortality. Neuronal hyperexcitability and pathological aggregates of tau and beta-amyloid underlie both dementia and seizure susceptibility. However, the relationship between seizure control and neuropathological changes in dementia remains poorly understood. This study investigates how active versus remote or no seizures relate to post-mortem neuropathology in a large multicentre cohort.
Data Highlights
Group
Deceased Proportion
Mean Age at Death (years)
Clinical Dementia Rating Score
Autopsy Cases
Active Seizures
56%
75.8
2.36
294
Remote Seizures
35%
77.9
1.90
151
No Seizures (Controls)
34%
80.8
1.69
5640
Key Findings
Active seizure participants had the highest mortality (56%) compared to remote (35%) and no seizures (34%) groups (P < 0.001).
Those with active seizures died younger (mean 75.8 years) and had more severe dementia (CDR 2.36) than other groups.
In primary AD diagnoses, active seizures correlated with more advanced Braak neurofibrillary stages and higher CERAD neuritic plaque density, indicating severe ATN pathology.
Active seizure participants showed greater neurodegeneration markers including cerebral and hippocampal atrophy and locus coeruleus hypopigmentation.
In non-AD dementias, active seizures were associated with worse AD co-pathology (higher Braak and Thal phases) but similar neurodegeneration compared to controls.
Frontotemporal lobar degeneration pathology was less prevalent in active seizure participants, while vascular, Lewy body, and other pathologies were comparable across groups.
Clinical Implications
Clinicians should maintain high vigilance for ongoing seizures in PWD, as active seizures indicate a worse prognosis with accelerated neurodegeneration and mortality. Early detection and management of seizures may be critical to potentially mitigate progression of neuropathology and cognitive decline. Post-mortem findings underscore the importance of seizure control in dementia care.
Conclusion
Active seizures in dementia patients are associated with earlier death and more severe neuropathological changes, particularly advanced AD pathology and neurodegeneration. These findings highlight the need for proactive seizure monitoring and management in this vulnerable population.
