Alzheimer Disease and Epilepsy

作者：Yi Fang, Xiaoli Si, Jiali Wang, Zhiyun Wang, Ying Chen, Yi Liu, Yaping Yan, Jun Tian, Baorong Zhang, Jiali Pu · 发表于：Neurology · 年份：2023 · DOI：10.1212/wnl.0000000000207423 · 被引用次数：65 · 研究领域：Alzheimer's disease research and treatments、Dementia and Cognitive Impairment Research、Epilepsy research and treatment

Background and Objectives Observational studies suggested a bidirectional relationship between Alzheimer’s disease (AD) and epilepsies. However, it remains debated whether and in which direction a causal association exists. The present study aims to explore the relationship between genetic predisposition to AD, CSF biomarkers of AD (Aβ42, pTau) and epilepsies with two-sample, bi-directional Mendelian randomization (MR) method. Methods Genetic instruments were obtained from large-scale genome-wide meta-analysis of AD (N case/proxy = 111,326, N control = 677,663), CSF biomarkers of AD (Aβ42 and pTau, N = 13,116) and epilepsy (N case = 15,212, N control = 29,677) of European ancestry. Epilepsy phenotypes included all epilepsy, generalized epilepsy, focal epilepsy, childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, generalized epilepsy with tonic-clonic seizures, focal epilepsy with hippocampal sclerosis, and lesion-negative focal epilepsy. Main analyses were performed using generalized summary data-based mendelian randomization (GSMR). Sensitivity analyses included IVW, MR-PRESSO, MR-Egger, weighted mode, and weighted median. Results For forward analysis, genetic predisposition to AD was associated with an increased risk of generalized epilepsy (OR = 1.053, 95% CI: 1.002 ∼ 1.105, P = 0.038), and focal epilepsy with hippocampal sclerosis (OR = 1.013, 95% CI: 1.004∼1.022, P = 0.004). These associations were consistent across sensitivity an...