Statin use and risk of dementia or Alzheimer's disease: a systematic review and meta-analysis of observational studies

Eur J Prev Cardiol. 2022 May 5;29(5):804-814. doi: 10.1093/eurjpc/zwab208.

Abstract

Aims: As the potential impact of statins on cognitive decline and dementia is still debated, we conducted a meta-analysis of observational studies to examine the effect of statin use on the risk of Alzheimer's disease (AD) and dementia.

Methods and results: PubMed, Cochrane, and EMBASE were searched since inception to January 2021. Inclusion criteria were: (i) cohort or case-control studies; (ii) statin users compared to non-users; and (iii) AD and/or dementia risk as outcome. Estimates from original studies were pooled using restricted maximum-likelihood random-effect model. Measure of effects were reported as odds ratio (OR) and 95% confidence intervals (CIs). In the pooled analyses, statins were associated with a decreased risk of dementia [36 studies, OR 0.80 (CI 0.75-0.86)] and of AD [21 studies, OR 0.68 (CI 0.56-0.81)]. In the stratified analysis by sex, no difference was observed in the risk reduction of dementia between men [OR 0.86 (CI 0.81-0.92)] and women [OR 0.86 (CI 0.81-0.92)]. Similar risks were observed for lipophilic and hydrophilic statins for both dementia and AD, while high-potency statins showed a 20% reduction of dementia risk compared with a 16% risk reduction associated with low-potency statins, suggesting a greater efficacy of the former, although a borderline statistical significance (P = 0.05) for the heterogeneity between estimates.

Conclusion: These results confirm the absence of a neurocognitive risk associated with statin treatment and suggest a potential favourable role of statins. Randomized clinical trials with an ad hoc design are needed to explore this potential neuroprotective effect.

Keywords: Alzheimer’s disease; Dementia; Meta-analysis; Observational studies; Statins.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / epidemiology
  • Alzheimer Disease* / prevention & control
  • Cognitive Dysfunction*
  • Dementia* / diagnosis
  • Dementia* / epidemiology
  • Dementia* / etiology
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
  • Male
  • Odds Ratio

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors