Genome Study Identifies Potential Bidirectional Association Between Alzheimer Disease and Epilepsy

New research published in the online issue of Neurology identified a potential genetic link between Alzheimer disease (AD) and epilepsy. According to an analysis of results from this study, individuals who have a genetic predisposition to developing AD also are at increased risk of developing generalized epilepsy and focal epilepsy with hippocampal sclerosis (HS); individuals with a genetic predisposition to focal epilepsy HS have an increased risk of developing AD.

This genome-wide association study (GWAS) used data from 2 previous GWASs to compare the genomes of 111,326 patients with AD against 677,663 people without AD, searching for small genetic variations between the groups. Researchers applied Mendelian randomization (MR) to determine potential causality between the identified variations and found that patients with AD were at 5.3% greater risk for generalized epilepsy and 1.3% greater risk for focal epilepsy HS. The same method was applied to data from the International League Against Epilepsy Consortium on Complex Epilepsies in 2018 to compare the genetic sequences of 15,212 patients with epilepsy against 29,677 people without epilepsy. Patients with focal epilepsy HS were found to be at almost 4-times greater risk for developing AD. Researchers also applied MR to data from a recent European Alzheimer & Dementia Biobank study of 13,116 participants and found that genetically predicted lower levels of amyloid in cerebrospinal fluid (CSF) were associated with increased risk of epilepsy.

“More effort should be made to screen for seizures in people with Alzheimer’s disease and to understand the impact of seizures on those facing these two challenging neurologic conditions.” said study author Jiali Pu, PhD.

Researchers noted one limitation of the study in that all participants were of European ancestry, meaning conclusions may not apply to other populations.