Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK.
Clinicum, Faculty of Medicine, FI-00014 University of Helsinki, Helsinki, Finland.
BMJ. 2019 Apr 17;365:l1495. doi: 10.1136/bmj.l1495.
To examine whether physical inactivity is a risk factor for dementia, with attention to the role of cardiometabolic disease in this association and reverse causation bias that arises from changes in physical activity in the preclinical (prodromal) phase of dementia.
Meta-analysis of 19 prospective observational cohort studies.
The Individual-Participant-Data Meta-analysis in Working Populations Consortium, the Inter-University Consortium for Political and Social Research, and the UK Data Service, including a total of 19 of a potential 9741 studies.
The search strategy was designed to retrieve individual-participant data from prospective cohort studies. Exposure was physical inactivity; primary outcomes were incident all-cause dementia and Alzheimer's disease; and the secondary outcome was incident cardiometabolic disease (that is, diabetes, coronary heart disease, and stroke). Summary estimates were obtained using random effects meta-analysis.
Study population included 404 840 people (mean age 45.5 years, 57.7% women) who were initially free of dementia, had a measurement of physical inactivity at study entry, and were linked to electronic health records. In 6.0 million person-years at risk, we recorded 2044 incident cases of all-cause dementia. In studies with data on dementia subtype, the number of incident cases of Alzheimer's disease was 1602 in 5.2 million person-years. When measured <10 years before dementia diagnosis (that is, the preclinical stage of dementia), physical inactivity was associated with increased incidence of all-cause dementia (hazard ratio 1.40, 95% confidence interval 1.23 to 1.71) and Alzheimer's disease (1.36, 1.12 to 1.65). When reverse causation was minimised by assessing physical activity ≥10 years before dementia onset, no difference in dementia risk between physically active and inactive participants was observed (hazard ratios 1.01 (0.89 to 1.14) and 0.96 (0.85 to 1.08) for the two outcomes). Physical inactivity was consistently associated with increased risk of incident diabetes (hazard ratio 1.42, 1.25 to 1.61), coronary heart disease (1.24, 1.13 to 1.36), and stroke (1.16, 1.05 to 1.27). Among people in whom cardiometabolic disease preceded dementia, physical inactivity was non-significantly associated with dementia (hazard ratio for physical activity assessed >10 before dementia onset 1.30, 0.79 to 2.14).
In analyses that addressed bias due to reverse causation, physical inactivity was not associated with all-cause dementia or Alzheimer's disease, although an indication of excess dementia risk was observed in a subgroup of physically inactive individuals who developed cardiometabolic disease.
研究身体活动不足是否是痴呆的一个风险因素，关注心血管代谢疾病在这一关联中的作用，以及在痴呆的临床前期（前驱期）发生的身体活动变化所导致的反向因果关系偏倚。
在工作人群中的个体参与者数据荟萃分析联盟、大学间社会和政治研究联合会以及英国数据服务机构中，对 19 项前瞻性观察队列研究进行了荟萃分析。
包括来自潜在的 9741 项研究中的 19 项的个体参与者数据荟萃分析在工作人群联盟、大学间社会和政治研究联合会以及英国数据服务机构中的个体参与者数据，共有 19 项。
搜索策略旨在从前瞻性队列研究中检索个体参与者数据。暴露因素为身体活动不足；主要结局是全因痴呆和阿尔茨海默病的发病情况；次要结局是心血管代谢疾病（即糖尿病、冠心病和中风）的发病情况。使用随机效应荟萃分析得出综合估计值。
研究人群包括 404840 人（平均年龄 45.5 岁，57.7%为女性），这些人最初没有痴呆，在研究开始时测量了身体活动不足，并且与电子健康记录相关联。在 600 万人年的风险中，我们记录了 2044 例全因痴呆的发病病例。在有痴呆亚型数据的研究中，在 520 万人年中，阿尔茨海默病的发病病例数为 1602 例。当身体活动不足在痴呆诊断前<10 年（即痴呆的临床前期）时，与全因痴呆（危险比 1.40，95%置信区间 1.23 至 1.71）和阿尔茨海默病（1.36，1.12 至 1.65）的发病风险增加相关。当通过评估痴呆发病前≥10 年的身体活动来最小化反向因果关系时，在活跃和不活跃的参与者之间，痴呆风险没有差异（两种结局的危险比分别为 1.01（0.89 至 1.14）和 0.96（0.85 至 1.08））。身体活动不足与新发糖尿病（危险比 1.42，1.25 至 1.61）、冠心病（1.24，1.13 至 1.36）和中风（1.16，1.05 至 1.27）的风险增加一致相关。在心血管代谢疾病先于痴呆发生的人群中，身体活动不足与痴呆无显著相关性（痴呆发病前>10 年评估的身体活动的危险比为 1.30，0.79 至 2.14）。
在分析因反向因果关系导致的偏倚时，身体活动不足与全因痴呆或阿尔茨海默病无关，尽管在一组患有心血管代谢疾病的身体不活跃个体中观察到痴呆风险增加的迹象。
