Statin use and dementia risk: a meta-analysis

Consumer concerns regarding potential adverse effects of statins on memory and/or cognitive changes are prevalent. Most of these concerns are based merely on case reports, however, they can compromise acceptance or adherence to statin medications essential to reduce atherosclerotic cardiovascular risk. With increasing body of evidence, short-term data suggest a lack of adverse effect of statins on cognition, while long-term data seem to support a beneficial role for statins in the prevention of dementia. On December 6, 2021, an updated systematic review and meta-analysis of all observational studies reporting data on the risk of Alzheimer’s disease (AD) and/or dementia in individuals treated with statins was published in the European Journal of Preventive Cardiology considering all  this background.

A total of 46 observational studies (38 cohort studies and 8 case–control studies) were included in the meta-analysis. All these studies were published between 2000 and January 2021. Samples sizes ranged from 123 to 2 004 692 patients, and 14 out of 46 studies reported a mean participant age ≥75 years old. All studies were of high methodological quality, with only one study reporting a Newcastle-Ottawa scale score of 5 points In total, 25 studies reporting adjusted estimates only for dementia risk, 10 only for AD risk, and 11 studies reporting estimates for both the outcomes.

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.

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.