Midlife vascular risk factors and the risk of Alzheimer's disease: a systematic review and meta-analysis

J Alzheimers Dis. 2014;42(4):1295-310. doi: 10.3233/JAD-140954.


Background/objective: We examine whether midlife vascular risk factors (VRFs) are associated with increased risk of incident Alzheimer's disease (AD) in a systematic review and meta-analysis of published cohort studies.

Methods: Original cohort studies were included if they reported adjusted combined odds ratio (COR) and corresponding 95% confidence intervals (CIs) or enough information to quantify the association between risk for AD in late-life and baseline VRFs of midlife.

Results: There were positive and significant associations between high blood pressure (COR 1.31; 95% CI: 1.01-1.70), hypercholesterolemia (COR 1.72; 95% CI: 1.32-2.24), obesity (COR 1.88; 95% CI: 1.32-2.69), and diabetes mellitus in midlife (COR 1.4; 95% CI: 1.25-1.57). Smoking and hyperhomocysteinemia (although only one high-quality paper) were also associated with an increased risk of AD generally.

Conclusions: These results strengthen the epidemiological evidence that VRFs of midlife significantly increase risk for AD.

Keywords: Alzheimer's disease; diabetes mellitus; high blood pressure; hypercholesterolemia; hyperhomocysteinemia; meta-analysis; midlife vascular risk factors; obesity; smoking; systematic review.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / physiopathology
  • Cerebrovascular Disorders / epidemiology*
  • Humans
  • Middle Aged
  • Risk Factors