Aspirin Use and Risk of Alzheimer’s Disease: A 2-Sample Mendelian Randomization Study

Abstract

Background: Observational studies have shown inconsistent findings of the relationships between aspirin use and the risk of Alzheimer’s disease (AD). Objective: Since residual confounding and reverse causality were challenging issues inherent in observational studies, we conducted a 2-sample Mendelian randomization analysis (MR) to investigate whether aspirin use was causally associated with the risk of AD. Methods: We conducted 2-sample MR analyses utilizing summary genetic association statistics to estimate the potential causal relationship between aspirin use and AD. Single-nucleotide variants associated with aspirin use in a genome-wide association study (GWAS) of UK Biobank were considered as genetic proxies for aspirin use. The GWAS summary-level data of AD were derived from a meta-analysis of GWAS data from the International Genomics of Alzheimer’s Project (IGAP) stage I. Results: Univariable MR analysis based on these two large GWAS data sources showed that genetically proxied aspirin use was associated with a decreased risk of AD (Odds Ratio (OR): 0.87; 95%CI: 0.77–0.99). In multivariate MR analyses, the causal estimates remained significant after adjusting for chronic pain, inflammation, heart failure (OR = 0.88, 95%CI = 0.78–0.98), or stroke (OR = 0.87, 95%CI = 0.77–0.99), but was attenuated when adjusting for coronary heart disease, blood pressure, and blood lipids. Conclusion: Findings from this MR analysis suggest a genetic protective effect of aspirin use on AD, possibly influenced by coronary heart disease, blood pressure, and lipid levels.

CSF proteomic profiling with amyloid/tau positivity identifies distinctive sex-different alteration of multiple proteins involved in Alzheimer’s disease

“…45 A recent meta-analysis study using Mendelian randomization to control for unknown confoundings confirmed these benefits on lowering AD risk, although the study also suggested the effect may be influenced by coronary heart disease, blood pressure, and blood lipids. 70 Besides nabumetone, melatonin may be a potential drug of AD in males which was reported to enhance hippocampal neurogenesis and improve memory function. 71 A meta-analysis of twenty-one clinical trials concluded that melatonin was beneficial in treatment of mild stage of AD with the significant improve of mini-mental state examination after 12 weeks of treatment.…”

Causal relationship between Alzheimer’s disease and cardiovascular disease: a bidirectional Mendelian randomization analysis

“…The treatment and management of cardioembolic stroke often involve improving cardiovascular health, which may enhance cerebral blood flow and reduce microvascular occlusions, thereby preventing the development of AD [ 37 , 38 ]. Therapeutic drugs, such as aspirin and other antiplatelet drugs [ 39 , 40 ], and rivaroxaban and other anticoagulants [ 41 ], might ameliorate cerebral microcirculation, alleviate neuroinflammation, and counteract Aβ deposition, thus decelerating the progression of AD. A diagnosis of cardioembolic stroke may prompt patients to make lifestyle changes, such as increasing physical activity, improving dietary habits, and reducing smoking, which might enhance brain health and reduce the incidence of AD [ 42 ].…”

Association of thrombopoietin-related drugs with thromboembolic events: Mendelian randomization and a real-world study

“…The summary statistics for smoking, hypertension, diabetes, HF, lung cancer (LC), breast cancer (BC), and lymphomas (these three cancer types with large sample sizes and high incidence rates represent tumors) were derived from the IEU Project. To maximize the strength and compensate for the lack of SNPs, we extracted individual SNPs for each trait concerning the significance and linkage disequilibrium threshold settings for Ding et al 23 To adjust pleiotropic effects across TPORDs traits, we performed 13 models in MVMR analyses: model 1 included all traits; models 2–13 included individual traits, in the order of OC, HRT, hypertension, diabetes, CHD, HF, AF, LC, BC, lymphomas, obesity, and smoking. GWAS summary-level data for TEE outcomes were obtained from FinnGen results, including VTE, DVT, PE, MI, and STR.…”