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Causal Link ID’d for Alzheimer Disease, Generalized Epilepsy

Genetic predisposition to Alzheimer’s also linked to increased risk of focal epilepsy with hippocampal sclerosis

By Elana Gotkine HealthDay Reporter

THURSDAY, May 25, 2023 (HealthDay News) — There is a causal link between Alzheimer disease (AD), amyloid pathology, and generalized epilepsy, according to a study published online May 24 in Neurology.

Yi Fang, M.D., from the Zhejiang University School of Medicine in China, and colleagues examined the association between genetic predisposition to AD, cerebrospinal fluid (CSF) biomarkers of AD (Aβ42, pTau), and epilepsies with two-sample, bidirectional Mendelian randomization methods. Genetic instruments were extracted from a genome-wide meta-analysis of AD (111,326 cases; 677,633 controls), CSF biomarkers of AD (13,116 cases), and epilepsy (15,212 cases and 29,677 controls) of European ancestry.

The researchers found that genetic predisposition to AD was associated with increased risk of generalized epilepsy and focal epilepsy with hippocampal sclerosis (odds ratios, 1.053 and 1.013, respectively). Across sensitivity analyses, these associations were consistent and were replicated using a separate set of single nucleotide polymorphisms from another genome-wide association study for AD. A suggestive effect of focal epilepsy with hippocampal sclerosis on AD was seen in reverse analysis (odds ratio, 3.994). In addition, increased risk of generalized epilepsy was seen in association with genetically predicted lower CSF Aβ42 (β = 0.090).

“We provide novel evidence that AD was causally linked to generalized epilepsy and focal epilepsy with hippocampal sclerosis,” the authors write. “Our finding highlights that AD and amyloid pathology gives rise to epilepsies. More effort should be made to screen seizure in AD and understand its clinical implications.”

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