{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T17:05:09Z","timestamp":1762103109396,"version":"build-2065373602"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Previous studies have shown that Alzheimer\u2019s disease (AD) can cause myocardial damage. However, whether there is a causal association between AD and non-ischemic cardiomyopathy (NICM) remains unclear. Using a comprehensive two-sample Mendelian randomization (MR) method, we aimed to determine whether AD and family history of AD (FHAD) affect left ventricular (LV) structure and function and lead to NICM, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The summary statistics for exposures [AD, paternal history of AD (PH-AD), and maternal history of AD (MH-AD)] and outcomes (NICM, HCM, DCM, and LV traits) were obtained from the large European genome-wide association studies. The causal effects were estimated using inverse variance weighted, MR-Egger, and weighted median methods. Sensitivity analyses were conducted, including Cochran\u2019s Q test, MR-Egger intercept test, MR pleiotropy residual sum and outlier, MR Steiger test, leave-one-out analysis, and the funnel plot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetically predicted AD was associated with a lower risk of NICM [odds ratio (OR) 0.9306, 95% confidence interval (CI) 0.8825\u20130.9813, <jats:italic>p<\/jats:italic> = 0.0078], DCM (OR 0.8666, 95% CI 0.7752\u20130.9689, <jats:italic>p<\/jats:italic> = 0.0119), and LV remodeling index (OR 0.9969, 95% CI 0.9940\u20130.9998, <jats:italic>p<\/jats:italic> = 0.0337). Moreover, genetically predicted PH-AD was associated with a decreased risk of NICM (OR 0.8924, 95% CI 0.8332\u20130.9557, <jats:italic>p<\/jats:italic> = 0.0011). MH-AD was also strongly associated with a decreased risk of NICM (OR 0.8958, 95% CI 0.8449\u20130.9498, <jats:italic>p<\/jats:italic> = 0.0002). Different methods of sensitivity analysis demonstrated the robustness of the results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study revealed that AD and FHAD were associated with a decreased risk of NICM, providing a new genetic perspective on the pathogenesis of NICM.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2024.1379865","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T04:49:05Z","timestamp":1717562945000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The causal effect of Alzheimer\u2019s disease and family history of Alzheimer\u2019s disease on non-ischemic cardiomyopathy and left ventricular structure and function: a Mendelian randomization study"],"prefix":"10.3389","volume":"15","author":[{"given":"Zhenjie","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiandong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wangping","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huazeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dehai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1016\/0002-9149(93)90547-p","article-title":"Autonomic nervous system activity in idiopathic dilated cardiomyopathy and in hypertrophic cardiomyopathy","volume":"71","author":"Ajiki","year":"1993","journal-title":"Am. 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