Do HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, commonly referred to as statins, cause dementia?

From the Guidelines

Statins do not cause dementia, and their use should not be deterred due to concerns about cognitive dysfunction or dementia. The most recent and highest quality study, published in 2024 in the journal Diabetes Care 1, found that several lines of evidence point against an association between statin use and cognitive decline. This study cited three large randomized trials of statin versus placebo where specific cognitive tests were performed, and no differences were seen between statin and placebo. Additionally, the study noted that 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.

Some key points to consider include:

• The potential benefits of statins in reducing cardiovascular risk outweigh the potential risks of cognitive decline
• Statins work by inhibiting an enzyme involved in cholesterol production in the liver, and while they can cross the blood-brain barrier, there's no established mechanism by which they would cause dementia
• If patients experience cognitive symptoms while taking statins, they should discuss these with their healthcare provider rather than discontinuing the medication on their own
• Other studies, such as those published in 2022 1 and 2023 1, also support the finding that statins do not cause dementia, and that fear of cognitive decline should not be a barrier to statin use in people with diabetes and a high risk for cardiovascular disease.

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)

Dementia is not explicitly mentioned in the drug label as a side effect of statins. However, cognitive impairment is reported, which may be related to dementia. The label states that cognitive impairment is rare, nonserious, and reversible upon statin discontinuation.

• The incidence of cognitive impairment is not specified.
• The relationship between statin use and dementia is not directly addressed in the label 2.

From the Research

Statins and Dementia

• The relationship between statins and dementia is not well-established, with some studies suggesting no significant link between the two 3, 4, 5.
• A study published in 2017 found that although cognitive decline has been reported anecdotally, its incidence was comparable to placebo in two RCTs with validated cognitive evaluations 3.
• Another study published in 2012 found that statin-induced cognitive changes are rare, and insufficient evidence is currently available to establish causality 6.
• The available evidence suggests that statins are generally well-tolerated, with a low frequency of adverse events, and that the potential benefits of statin therapy in reducing cardiovascular risk outweigh the possible adverse effects 3, 4, 5, 7.

Adverse Effects of Statins

• The most common adverse events associated with statins are mild gastrointestinal symptoms, elevated serum transaminase levels, and myopathy 4, 5, 7.
• Statins may also increase the risk of developing diabetes, particularly in patients taking high-dose statins and those with multiple risk factors for diabetes 6.
• The risk of drug-drug interactions with statins is a relevant factor in determining their safety profile, particularly when used in combination with other lipid-lowering agents or medications for concomitant conditions 7.