Lee Liam, Walker Rosie, Whiteley William
University of Edinburgh, Edinburgh, UK.
Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK.
F1000Res. 2025 Feb 7;11:565. doi: 10.12688/f1000research.121604.2. eCollection 2022.
Although observational studies demonstrate that higher levels of vascular risk factors are associated with an increased risk of dementia, these associations might be explained by confounding or other biases. Mendelian randomization (MR) uses genetic instruments to test causal relationships in observational data. We sought to determine if genetically predicted modifiable risk factors (type 2 diabetes mellitus, low density lipoprotein cholesterol, high density lipoprotein cholesterol, total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, body mass index, and circulating glucose) are associated with dementia by meta-analysing published MR studies. Secondary objectives were to identify heterogeneity in effect estimates across primary MR studies and to compare meta-analysis results with observational studies.
MR studies were identified by systematic search of Web of Science, OVID and Scopus. We selected primary MR studies investigating the modifiable risk factors of interest. Only one study from each cohort per risk factor was included. A quality assessment tool was developed to primarily assess the three assumptions of MR for each MR study. Data were extracted on study characteristics, exposure and outcome, effect estimates per unit increase, and measures of variation. Effect estimates were pooled to generate an overall estimate, I and Cochrane Q values using fixed-effect model.
We screened 5211 studies and included 12 primary MR studies after applying inclusion and exclusion criteria. Higher genetically predicted body mass index was associated with a higher odds of dementia (OR 1.03 [1.01, 1.05] per 5 kg/m increase, one study, p=0.00285). Fewer hypothesized vascular risk factors were supported by estimates from MR studies than estimates from meta-analyses of observational studies.
Genetically predicted body mass index was associated with an increase in risk of dementia.
尽管观察性研究表明，较高水平的血管危险因素与痴呆风险增加相关，但这些关联可能由混杂因素或其他偏倚所解释。孟德尔随机化（MR）利用基因工具来检验观察性数据中的因果关系。我们试图通过对已发表的MR研究进行荟萃分析，来确定基因预测的可改变危险因素（2型糖尿病、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、总胆固醇、甘油三酯、收缩压、舒张压、体重指数和循环葡萄糖）是否与痴呆相关。次要目标是识别各主要MR研究中效应估计值的异质性，并将荟萃分析结果与观察性研究进行比较。
通过系统检索科学网、OVID和Scopus来识别MR研究。我们选择了调查感兴趣的可改变危险因素的主要MR研究。每个危险因素每个队列仅纳入一项研究。开发了一种质量评估工具，主要用于评估每项MR研究的MR的三个假设。提取了关于研究特征、暴露和结局、每单位增加的效应估计值以及变异度量的数据。使用固定效应模型汇总效应估计值，以生成总体估计值、I²和Cochrane Q值。
我们筛选了5211项研究，在应用纳入和排除标准后纳入了12项主要MR研究。基因预测的体重指数越高，痴呆的几率越高（每增加5kg/m²，比值比为1.03[1.01,1.05]，一项研究，p = 0.00285）。与观察性研究的荟萃分析估计值相比，MR研究估计值支持的假设血管危险因素较少。
基因预测的体重指数与痴呆风险增加相关。
