Systematic evaluation of the associations between environmental risk factors and dementia: An umbrella review of systematic reviews and meta‐analyses

Introduction Dementia is a heterogeneous neurodegenerative disease, whose etiology results from a complex interplay between environmental and genetic factors. Methods We searched PubMed to identify meta‐analyses of observational studies that examined associations between nongenetic factors and dementia. We estimated the summary effect size using random‐effects and fixed‐effects model, the 95% CI, and the 95% prediction interval. We assessed the between‐study heterogeneity (I‐square), evidence of small‐study effects, and excess significance. Results A total of 76 unique associations were examined. By applying standardized criteria, seven associations presented convincing evidence. These associations pertained to benzodiazepines use, depression at any age, late‐life depression, and frequency of social contacts for all types of dementia; late‐life depression for Alzheimer's disease; and type 2 diabetes mellitus for vascular dementia and Alzheimer's disease. Discussion Several risk factors present substantial evidence for association with dementia and should be assessed as potential targets for interventions, but these associations may not necessarily be causal.