APOE ε4 associates with epilepsy, dementia, and higher mortality
In UK Biobank participants, carrying one or two APOE ε4 copies was linked to approximately 80% and 225% higher risks of post-epilepsy dementia.
Human Genetics
In a cohort of UK Biobank participants, researchers evaluated how apolipoprotein E (APOE) ε4 status relates to epilepsy risk, post-epilepsy dementia, and mortality. They grouped participants by their number of APOE ε4 alleles and evaluated outcomes using Cox proportional hazards models. The APOE ε4 allele was associated with an increased risk of epilepsy, particularly late-onset epilepsy among homozygous carriers. Among participants with epilepsy, carrying APOE ε4 was linked to higher rates of subsequent dementia and premature death. Having one copy was associated with an approximately 80% higher risk of dementia after epilepsy, whereas having two copies was associated with an approximately 225% higher risk. Homozygous carriers also experienced an approximately 39% higher risk of death, particularly from neurological causes, while single-copy carriers showed a trend toward increased mortality.
Why it matters
Late-onset epilepsy and dementia frequently co-occur in aging populations. These findings highlight APOE ε4 as a common genetic risk factor that shapes both seizure susceptibility and long-term neurodegenerative prognosis.
Caveats
The observational design of the UK Biobank cohort establishes correlations rather than direct causal mechanisms. In addition, the proportion of APOE ε4 carriers in post-stroke epilepsy varied across different clinical conditions.
The paper
Association of apolipoprotein E gene with risk, cognition, and prognosis of epilepsy