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Link Between Alzheimer Disease and Epilepsy Development Risk Found
A causal link was found between Alzheimer Disease (AD), amyloid pathology, and generalized epilepsy in a recent mendelian randomization study published in the journal Neurology. Patients who have focal epilepsy with hippocampal sclerosis are at nearly 4 times the risk of developing AD compared to those without epilepsy, the study found.
“Our research found that not only are people with Alzheimer disease more likely to develop epilepsy, but also that those with focal epilepsy, which accounts for more than half of all cases of epilepsy, were more likely to develop Alzheimer disease,” said study author Jiali Pu, PhD, Zhejiang University School of Medicine in Hangzhou, China, in a news release. “More effort should be made to screen for seizures in people with Alzheimer disease and to understand the impact of seizures on those facing these 2 challenging neurologic conditions.”
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Researchers analyzed gene variations in 111,326 people with AD, 677,663 people without AD, then compared 15,212 people with epilepsy, matched to the genes of 29,677 people without epilepsy. Researchers used Mendelian randomization to determine if there was cause and effect between the genetic variations and the risk of epilepsy. Researchers also examined 13,116 participants with genetic data on the levels of the AD biomarker amyloid in their cerebrospinal fluid and found that genes that predicted a lower amount of the biomarker were linked to an increased risk of generalized epilepsy. Epilepsy phenotypes, such as childhood absence epilepsy, juvenile absence epilepsy, focal epilepsy with hippocampal sclerosis, and lesion-negative focal epilepsy, among others, were included. Several sensitivity analyses were also performed, such as IVW, MR-PRESSO, MR-Egger, weighted mode, and weighted median.
The results showed that a genetic predisposition to AD was associated with a 5.3% increased risk of generalized epilepsy (OR = 1.053, 95% CI: 1.002 ∼ 1.105, P = 0.038) and a 1.3% increased risk of focal epilepsy with hippocampal sclerosis (OR = 1.013, 95% CI: 1.004∼1.022, P = 0.004). The reverse analysis showed a suggestive effect of focal epilepsy with hippocampal sclerosis on AD where patients had almost 4 times the risk compared to those without focal epilepsy with hippocampal sclerosis (OR = 3.994, 95%CI: 1.172∼13.613, P = 0.027). Additionally, genetically predicted lower levels of CSF Aβ42 were associated with an increased risk of generalized epilepsy (β = 0.090, 95% CI: 0.022 ∼ 0.158, P = 0.010).
Researchers note that all participants included in the study were of European descent. Thus, these results may not be widely applicable to people of other backgrounds and ethnicities. “Studies enrolling larger sample size are needed to replicate the current findings,” researchers wrote in the study, “…Future studies using GWAS data from other ethnicities (e.g., Biobank Japan, China Kadoorie Biobank) are needed to test the generalizability across different populations.
The study was funded by the Chinese National Natural Science Foundation and Zhejiang Province.
