Can Atorvastatin (HMG-CoA reductase inhibitor) cause dementia?

From the Guidelines

There is no clear evidence that atorvastatin causes dementia, and the most recent studies suggest that statins like atorvastatin may not have an adverse effect on cognition 1. The relationship between cholesterol-lowering medications and brain function is complex, as cholesterol plays important roles in brain health, but so does maintaining good cardiovascular health. Several lines of evidence point against the association between statins and cognitive dysfunction, including three large randomized trials of statin versus placebo where specific cognitive tests were performed, and no differences were seen between statin and placebo 1. Additionally, the most recent systematic review of the U.S. Food and Drug Administration’s (FDA’s) postmarketing surveillance databases, randomized controlled trials, and cohort, case-control, and cross-sectional studies evaluating cognition in individuals receiving statins found that published data do not reveal an adverse effect of statins on cognition 1. Some key points to consider include:

• The benefits of taking atorvastatin for people with high cholesterol or cardiovascular disease typically outweigh potential risks.
• If you experience any cognitive changes while taking atorvastatin, discuss these with your healthcare provider rather than stopping the medication on your own.
• Your doctor can evaluate your symptoms, consider alternative explanations, and potentially adjust your treatment if necessary. It is essential to prioritize the single most recent and highest quality study, which in this case is the 2024 study published in Diabetes Care 1. This study provides the most up-to-date evidence on the relationship between statins and cognitive function, and its findings should be given the most weight in clinical decision-making.

From the FDA Drug Label

There have been rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with the use of all statins.

• Cognitive impairment was generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks)
• The term dementia is not explicitly mentioned in the label, but cognitive impairment can be a symptom of dementia.
• Based on the information provided, it can be inferred that atorvastatin may be associated with cognitive impairment, but it is not clear if this is directly related to dementia.
• A conservative clinical decision would be to monitor patients for signs of cognitive impairment, as the evidence is unclear and equivocal 2

From the Research

Atorvastatin and Dementia

• The relationship between atorvastatin and dementia is complex, with some studies suggesting a potential link between the two 3.
• A pharmacovigilance analysis using real-world data from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) found that memory loss was a frequent side effect of atorvastatin 3.
• However, other studies have found that statin use, including atorvastatin, may be associated with a decreased risk of dementia 4.
• A meta-analysis of 31 eligible studies found that statin use was associated with a decreased risk of dementia, with a relevant risk (RR) of 0.85 (95% CI, 0.80-0.89) 4.
• Another study found that ongoing statin use was not associated with cognitive decline or dementia progression in older adults with mild-moderate Alzheimer's disease 5.

Statin Use and Cognitive Decline

• A longitudinal registry-based cohort study found that statin use was associated with a slower cognitive decline in patients with Alzheimer's and mixed dementia 6.
• The study found that taking one defined daily dose of statins on average was associated with 0.63 more MMSE points after 3 years compared to no use of statins (95% CI: 0.33;0.94) 6.
• However, another study found that statin therapy was not associated with incident dementia, mild cognitive impairment, or declines in individual cognition domains in adults ≥65 years of age 7.
• The study found that baseline neurocognitive ability was an effect modifier for the associations of statins with dementia and memory change 7.

Conclusion is not allowed, so the response will be ended here.