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

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.

Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice

“…In agreement, defects in brain cholesterol homeostasis can be linked to the prevalence of neurodegenerative diseases such AD, Parkinson’s disease, Niemann–Pick disease type C, and Huntington’s disease, among others [ 31 , 38 , 39 , 40 ]. Particularly, early studies in AD pathology described elevated levels of cholesterol in the brain of AD patients, which agrees with the epidemiological and observational studies in which statins, a cholesterol-lowering drug, seem to exhibit a positive effect against AD incidence [ 41 , 42 , 43 , 44 ]. Conversely, other works found a reduced content of cholesterol in several cortical areas of the human brain [ 45 ], but also in the hippocampus of SAMP8 mice [ 37 ].…”

Shared Molecular Mechanisms among Alzheimer’s Disease, Neurovascular Unit Dysfunction and Vascular Risk Factors: A Narrative Review

“…Oral antidiabetics and insulin seem able to reduce cognitive impairment in AD [ 156 ]. Statin use is not associated with an increased risk of cognitive impairment, and some small observational studies seem to associate this treatment with a potentially favourable role in the setting of AD [ 157 ]. Long-term oxygen therapy, also, seems to improve cognition hypoxemic patients affected by AD [ 128 ].…”

High-Throughput Clinical Trial Emulation with Real World Data and Machine Learning: A Case Study of Drug Repurposing for Alzheimer’s Disease

“…Atorvastatin is used to treat high cholesterol and triglyceride levels, shows potentially beneficial but not significant effects on AD in 27,28 . We observed that atorvastatin was associated with a 21% reduced risk of AD (HR 0.79, 95% CI 0.77-0.81) in OneFlorida and a 12% reduced risk of AD (HR 0.88, 95% CI 0.85-0.90) in MarketScan.…”