Genetic Evidence for Causal Association Between Atrial Fibrillation and Dementia: A Mendelian Randomization Study

• DOI: 10.1161/jaha.123.029623
• Publication Date: 2023-08-07T09:37:09Z
• Authors: Mingxiao Li; Chao Jiang; Yiwei Lai; Yufeng Wang; Manlin Zhao; Sitong Li; Xiaodong Peng; Liu He; Xueyuan Guo; Songnan Li; Nian Liu; Chenxi Jiang; Ribo Tang; Caihua Sang; Deyong Long; Xin Du; Jianzeng Dong; Changsheng Ma
• Keywords: Mendelian Randomization; Vascular dementia; Stroke

Background The knowledge gap regarding whether the correlation between atrial fibrillation (AF) and dementia in observational studies is causation or driven by other shared risk factors remains substantially unfilled. Methods Results We performed a comprehensive 2-sample Mendelian randomization study to evaluate causal effect of AF on overall its subtypes, including vascular dementia, Alzheimer Lewy body frontotemporal dementia. primary results inverse variance-weighted analyses were further validated various sensitivity analyses. Additionally, we conducted multivariable examine 10 candidate mediators association Genetic predisposition was modestly associated with an increased (odds ratio, 1.140 [95% CI, 1.023-1.271]; P=0.018) strongly 1.350 1.076-1.695]; P=0.010). Genetically predicted indicated neutral effects In analysis, total remarkably attenuated adjusting for genetic ischemic stroke 1.068 0.953-1.197]; P=0.259) low cardiac output 1.046 0.926-1.181]; P=0.475), indicating that genetically potentially mediated output. independent cerebral small-vessel disease brain volume phenotypes. Conclusions Our findings provided novel evidence supporting Future clinical trials are warranted potential role appropriate management prevention.