Do 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, commonly referred to as statins, increase the risk of cognitive impairment or dementia?

From the Guidelines

No, statins do not increase the risk of cognitive impairment or dementia based on current evidence. In fact, several lines of evidence point against this association, as detailed in 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 patients receiving statins 1.

Key Points

• Statins are commonly prescribed cholesterol-lowering medications like atorvastatin (Lipitor), simvastatin (Zocor), and rosuvastatin (Crestor).
• They are typically taken daily at doses ranging from 5-80 mg depending on the specific medication and patient needs.
• Patients taking statins should continue their prescribed regimen without concern about cognitive effects, but should report any unusual memory issues or cognitive changes to their doctor, as these could be related to other factors.
• The benefits of statins in preventing cardiovascular disease generally outweigh any potential risks for most patients prescribed these medications.

Evidence Summary

The most recent systematic review found that published data do not reveal an adverse effect of statins on cognition 1. Additionally, three large randomized trials of statin versus placebo where specific cognitive tests were performed, and no differences were seen between statin and placebo.

Clinical Implications

Patients with diabetes at high risk for ASCVD should not be deterred from using statins due to concerns about cognitive dysfunction or dementia. The protective effect of statins on cognition is thought to be due to their ability to reduce inflammation and improve blood flow to the brain. By lowering cholesterol levels, statins may also help prevent the formation of amyloid plaques associated with Alzheimer's 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) Rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. 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)

Cognitive Impairment and Statin Use:

• Key Finding: Rare reports of cognitive impairment associated with statin use.
• Characteristics: Generally nonserious and reversible upon statin discontinuation.
• Symptom Onset and Resolution: Variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).
• Studies: Reported in postmarketing experience with atorvastatin 2 and simvastatin 3.

Clinical Decision: While rare, cognitive impairment is a potential adverse effect of statin use. However, the available evidence suggests that it is generally reversible upon discontinuation of the statin. Therefore, caution should be exercised when prescribing statins, especially in patients with a history of cognitive impairment or dementia.

From the Research

Statins and Cognitive Impairment

• The relationship between statins and cognitive impairment is complex, with some studies suggesting a potential link to reversible cognitive impairment in some patients 4, 5.
• However, other studies have found that statins may actually decrease the risk of dementia, Alzheimer's disease, and improve cognitive impairment in some cases 4, 6.
• Randomized controlled trials have failed to confirm a significant cognitive-impairing effect of statins, and the evidence for both positive and negative effects is compelling 4, 7, 6, 5, 8.

Mechanisms and Modifying Factors

• The mechanisms underlying the potential cognitive effects of statins are not fully understood, but may involve the reduction of low-density lipoprotein cholesterol (LDL-C) and the modification of individual and statin-related factors 7.
• Factors such as age, cardiovascular disease, and baseline cognitive function may influence the cognitive effects of statins, and healthcare providers should be aware of these factors when prescribing statins 4, 7, 6.

Current Evidence and Recommendations

• The current evidence suggests that statins are not likely to cause significant cognitive impairment in most patients, but rare cases of reversible cognitive impairment have been reported 5, 8.
• Healthcare providers should weigh the cardiovascular benefits of statins against the potential risks of cognitive decline on an individual basis, and consider alternative treatments or closer monitoring for patients at high risk of cognitive impairment 6, 8.