Background The association between serum folate deficiency and the risk of dementia in old age is unclear, perhaps owing to small sample sizes, the competing risk of mortality or reverse causation. Objective To examine the associations between serum folate deficiency and the risks of incident dementia and all-cause mortality in a large national sample of older adults. Methods A prospective cohort aged 60–75 years (n=27 188) without pre-existing dementia for at least 10 years, was tested for serum concentrations of folate and followed up for dementia or all-cause mortality. Serum folate deficiency was classified as present (<4.4 ng/mL), otherwise absent. HRs and 95% CIs from competing risks Cox models were fitted to quantify the associations between serum folate deficiency and the risks of dementia and all-cause mortality. To examine reverse causation, the analysis was stratified by duration of follow-up. Findings The presence compared with the absence of serum folate deficiency was associated with higher risks of dementia (HR=1.68; 95% CI 1.32 to 2.13; p<0.001) and all-cause mortality (HR=2.98; 95% CI 2.52 to 3.52; p<0.001). Evidence for reverse causation were moderate for dementia and mild for all-cause mortality. Conclusions Serum concentrations of folate may function as a biomarker used to identify those at risk of dementia and mortality; however, reverse causation is likely. Further research is needed to examine the role of serum folate deficiency in dementia aetiology. Clinical implications Serum folate deficiency in older adults requires monitoring and treatment for preventative measures and/or as part of implemented therapeutic strategies. Data are available on reasonable request.

中文翻译：

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血清叶酸缺乏与痴呆和全因死亡的风险：一项全国老年研究

背景 血清叶酸缺乏与老年痴呆风险之间的关联尚不清楚，可能是由于样本量小、死亡风险竞争或反向因果关系。目的 在全国老年人的大样本中检查血清叶酸缺乏与痴呆症和全因死亡率风险之间的关联。方法 对年龄 60-75 岁（n=27 188）且至少 10 年没有痴呆症的前瞻性队列进行血清叶酸浓度检测，并对痴呆或全因死亡率进行随访。血清叶酸缺乏被分类为存在（<4.4 ng/mL），否则不存在。对来自竞争风险 Cox 模型的 HR 和 95% CI 进行拟合，以量化血清叶酸缺乏与痴呆和全因死亡率风险之间的关联。为了检查反向因果关系，分析按随访持续时间进行分层。结果 与不存在血清叶酸缺乏相比，存在较高的痴呆风险（HR=1.68；95% CI 1.32 至 2.13；p<0.001）和全因死亡率（HR=2.98；95% CI 2.52 至 3.52） ；p<0.001）。痴呆症的反向因果关系证据为中度，全因死亡率的反向因果关系证据为轻度。结论 血清叶酸浓度可以作为生物标志物，用于识别那些有痴呆和死亡风险的人；然而，反向因果关系也可能存在。需要进一步的研究来检查血清叶酸缺乏在痴呆病因学中的作用。临床意义 老年人血清叶酸缺乏症需要监测和治疗以采取预防措施和/或作为实施治疗策略的一部分。可根据合理要求提供数据。