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

Alzheimers Dement. 2017 Apr;13(4):406-418. doi: 10.1016/j.jalz.2016.07.152. Epub 2016 Sep 4.


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.

Keywords: Alzheimer's disease; Dementia; Epidemiology; Risk factors; Umbrella review.

Publication types

  • Review

MeSH terms

  • Dementia / complications
  • Dementia / drug therapy
  • Dementia / epidemiology*
  • Humans
  • Meta-Analysis as Topic
  • Risk Factors
  • Systematic Reviews as Topic