Association of Stress with Risk of Dementia and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis

Background Although many studies have investigated the association between stress and risk of dementia, findings are inconsistent due to the variation in the measures used to assess stress. Objective We conducted a systematic review and meta-analysis to investigate the association between psychological stress (including neuroticism, stressful life events, and perceived stress) and the risk of incident dementia and mild cognitive impairment in adults. Methods PsycINFO, Embase, and MEDLINE were searched to October 2020 for eligible observational, prospective studies. Of the 1,607 studies screened, 26 (24 unique cohorts) were included in the qualitative analysis and 16 (15 unique cohorts) were included in the quantitative analysis. Results Across studies, higher perceived stress was significantly associated with an increased risk of mild cognitive impairment (Cases/Total N = 207/860: hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 1.03-1.38) and all-cause dementia (Cases/Total N = 203/1,882: HR = 1.44, 95% CI = 1.07-1.95). Exposure to two or more stressful life events (versus none) was significantly associated with an increased risk of all-cause dementia (Cases/Total N = 3,354/11,597: HR = 1.72, 95% CI = 1.14-2.60), while one or more stressful life events was not. Higher neuroticism was significantly associated with an increased risk of Alzheimer's disease dementia (Cases/Total N = 497/4,771: HR = 1.07, 95% CI = 1.01-1.12), but not all-cause dementia. Conclusion This review suggests that psychological stress in adulthood is associated with an increased risk of dementia. Further research is needed to clarify the mechanisms underlying these associations.