Statin use and risk of dementia: a systematic review and meta-analysis of observational studies

Abstract

Background: Dementia affects over 55 million individuals worldwide, with projections indicating a substantial increase in prevalence in the coming decades. Statins are widely prescribed for cardiovascular prevention and have been proposed to exert pleiotropic effects, including anti-inflammatory and neuroprotective mechanisms. However, evidence regarding their role in reducing dementia risk remains inconsistent across studies. Objective: To systematically evaluate and quantify the association between statin use and the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia. Methods: A systematic review and meta-analysis of observational studies was conducted in accordance with PRISMA guidelines. Electronic databases, including PubMed, Embase, Cochrane Library, Scopus, and Web of Science, were searched from inception to recent years. Eligible studies included cohort and case–control designs comparing statin users with non-users and reporting dementia-related outcomes. Two independent reviewers performed study selection, data extraction, and risk of bias assessment. Pooled effect estimates were calculated using random-effects models, and results were expressed as hazard ratios (HRs), odds ratios (ORs), or risk ratios (RRs) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted according to statin type, duration of exposure, geographic region, and presence of comorbidities such as type 2 diabetes mellitus. Results: Statin use was associated with a consistent reduction in the risk of all-cause dementia. A similar protective association was observed for Alzheimer’s disease. In contrast, no clear or statistically significant association was identified for vascular dementia. Subgroup analyses suggested a more pronounced protective effect among individuals with type 2 diabetes, those with longer duration of statin use, and populations from specific geographic regions. Differences were also observed according to statin type, with some agents demonstrating greater potential neuroprotective effects. Sensitivity analyses supported the consistency and robustness of these findings despite heterogeneity among studies. Conclusion: Statin therapy is associated with a reduced risk of all-cause dementia and Alzheimer’s disease, supporting a potential neuroprotective effect beyond lipid-lowering properties. Although causality cannot be established due to the observational nature of included studies, the consistency of findings across large populations and subgroup analyses strengthens the evidence. Further randomized controlled trials are needed to confirm these associations and to clarify the role of statins in dementia prevention.