Are there high-quality studies linking HMG-CoA reductase inhibitors (statins) and dementia?

From the Guidelines

The current evidence does not support a link between statin use and an increased risk of dementia, and statins should not be withheld from individuals with diabetes at high risk for ASCVD due to concerns about cognitive decline. The most recent and highest quality study, published in 2024 1, found that several lines of evidence point against an association between statin use and cognitive dysfunction or dementia. This study, along with others 1, highlights that large randomized trials of statin versus placebo have shown no differences in cognitive function between the two groups. Additionally, the systematic review of the U.S. Food and Drug Administration’s postmarketing surveillance databases, randomized controlled trials, and cohort, case-control, and cross-sectional studies evaluating cognition in patients receiving statins found no adverse effect of statins on cognition.

Key points to consider:

• Multiple studies have found no association between statin use and cognitive decline or dementia 1
• The FDA postmarketing surveillance databases have revealed a low reporting rate for cognitive-related adverse events with statin therapy, similar to rates seen with other commonly prescribed cardiovascular medications 1
• Statins may have a protective effect against dementia due to their vascular protective properties and anti-inflammatory effects
• If concerned about cognitive effects while taking a statin, patients should discuss their concerns with their healthcare provider, who may recommend continuing the current statin, switching to a different statin, adjusting the dose, or considering alternative cholesterol-lowering approaches depending on their cardiovascular risk profile and specific symptoms.

From the Research

Studies on HMG-CoA Reductase Inhibitors (Statins) and Dementia

• There are several studies examining the relationship between statin use and dementia risk, with some indicating a potential association between statin use and reduced dementia risk 2, 3, 4.
• A 2020 systematic review and meta-analysis found that statins may have a small benefit in delaying progression in Alzheimer's dementia, although the evidence was insufficient to fully evaluate the efficacy of statins in people with dementia 2.
• A 2018 dose-response meta-analysis found that statin use was associated with a decreased risk of dementia, with a 20% reduction in dementia risk per 1 year of statin use and an 11% reduction per 5-mg mean daily dose increase 3.
• A 2020 meta-analysis of observational studies found that statin use was associated with a lower risk of all-caused dementia, with a risk ratio of 0.83 (95% CI 0.79-0.87) 4.
• However, a 2023 study found that ongoing statin use was not associated with cognitive decline or dementia progression in older adults with mild-moderate Alzheimer's disease, and was also not associated with adverse events 5.
• An earlier 2009 Cochrane review found that there was no evidence to recommend statins for the prevention of dementia, with two randomized controlled trials showing no difference in incidence of dementia between statin and placebo groups 6.

Key Findings

• The evidence on the relationship between statin use and dementia risk is mixed, with some studies suggesting a potential benefit and others finding no association.
• The quality of the evidence varies, with some studies having methodological limitations or inconsistent findings.
• Further research is needed to fully understand the relationship between statin use and dementia risk, and to inform prescribing decisions for patients with dementia 2, 3, 4, 5, 6.