Association of apolipoprotein E gene with risk, cognition, and prognosis of epilepsy

Previous experimental studies suggested a link between the apolipoprotein E (APOE) gene and epilepsy. However, clinical studies have failed to reach a definitive conclusion on the association. We conducted a cohort study to investigate the clinical correlation between APOE ε4 and epilepsy. This study was based on the UK Biobank. Participants were divided according to the number of APOE ε4 carriers. A Cox proportional hazards model was used to analyse the association between APOE ε4 and the risk of epilepsy, and the association between APOE ε4 and dementia after epilepsy, and the association between APOE ε4 and death. The presence of the APOE ε4 allele was associated with an increased risk of epilepsy, particularly late-onset epilepsy, but the difference in the proportion of APOE ε4 carriers compared with controls in post-stroke epilepsy varied by condition. APOE ε4 carriers were found to have a higher likelihood of dementia following epilepsy onset, with those carrying one copy of the APOE ε4 allele having an approximately 80% higher risk of dementia after epilepsy, and those carrying two copies of the APOE ε4 allele having an approximately 225% higher risk of dementia after epilepsy. APOE ε4 carriers with epilepsy also showed an elevated risk of death, with a trend toward increased risk in those carrying one copy of the APOE ε4 allele and an approximately 39% higher risk of death in those carrying two copies of the APOE ε4 allele. The APOE ε4 allele was associated with an increased risk of epilepsy, particularly late-onset epilepsy among homozygous carriers. Among participants with epilepsy, APOE ε4 carrier status was associated with an increased risk of dementia and premature death, particularly death from neurological causes.