From the Epidemiology and Public Health Group (K.B., L.J., L.C.P., J.D., D.M.), University of Exeter Medical School, Royal Devon & Exeter Hospital, Exeter, UK; UConn Center on Aging (G.A.K., R.H.F., D.M.), University of Connecticut, Farmington, CT; and National Institute on Aging (L.F.), Baltimore, MD.
Neurology. 2019 Mar 19;92(12):e1387-e1394. doi: 10.1212/WNL.0000000000007136. Epub 2019 Feb 15.
To estimate effects of vitamin D levels on incident delirium hospital admissions using inherited genetic variants in mendelian randomization models, which minimize confounding and exclude reverse causation.
Longitudinal analysis using the UK Biobank, community-based, volunteer cohort (2006-2010) with incident hospital-diagnosed delirium (ICD-10 F05) ascertained during ≤9.9 years of follow-up of hospitalization records (to early 2016). We included volunteers of European descent aged 60-plus years by end of follow-up. We used single-nucleotide polymorphisms previously shown to increase circulating vitamin D levels, and variants. Cox competing models accounting for mortality were used.
Of 313,121 participants included, 544 were hospitalized with delirium during follow-up. Vitamin D variants were protective for incident delirium: hazard ratio = 0.74 per 10 nmol/L (95% confidence interval 0.62-0.87, = 0.0004) increase in genetically instrumented vitamin D, with no evidence for pleiotropy (mendelian randomization-Egger > 0.05). Participants with ≥1 ε4 allele were more likely to develop delirium (e.g., ε4ε4 hazard ratio = 3.73, 95% confidence interval 2.68-5.21, = 8.0 × 10 compared to ε3ε3), but there was no interaction with vitamin D variants.
In a large community-based cohort, there is genetic evidence supporting a causal role for vitamin D levels in incident delirium. Trials of correction of low vitamin D levels in the prevention of delirium are needed.
利用孟德尔随机化模型中的遗传变异来估计维生素 D 水平对新发谵妄入院的影响，该模型可以最大限度地减少混杂并排除反向因果关系。
采用英国生物库的纵向分析，该生物库是一个基于社区的志愿者队列（2006-2010 年），在随访期间通过住院记录（至 2016 年初）确定了新发的医院诊断为谵妄（ICD-10 F05）。我们纳入了随访结束时年龄在 60 岁以上的欧洲血统志愿者。我们使用了先前显示可增加循环维生素 D 水平的单核苷酸多态性，以及其他变体。使用考虑到死亡率的 Cox 竞争模型。
在纳入的 313121 名参与者中，544 人在随访期间因谵妄住院。维生素 D 变体对新发谵妄具有保护作用：每增加 10 nmol/L 的遗传因素导致维生素 D 增加，风险比为 0.74（95%置信区间为 0.62-0.87， = 0.0004），且没有证据表明存在多效性（孟德尔随机化-Egger > 0.05）。携带至少 1 个 ε4 等位基因的患者更容易发生谵妄（例如，ε4ε4 风险比 = 3.73，95%置信区间为 2.68-5.21， = 8.0 × 10 与 ε3ε3 相比），但与维生素 D 变体无交互作用。
在一项大型基于社区的队列研究中，有遗传证据支持维生素 D 水平与新发谵妄之间存在因果关系。需要进行纠正低维生素 D 水平以预防谵妄的试验。
