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

From the Guidelines

Statins do not increase dementia risk, and current evidence suggests they may have a protective effect against dementia in some individuals. The most recent and highest quality study, published in 2024, found that statins do not have an adverse effect on cognitive function or dementia risk 1. This study, along with others, including a 2023 systematic review, have consistently shown that statins do not increase the risk of dementia 1. In fact, the ability of statins to reduce vascular disease, a risk factor for certain types of dementia, may contribute to their potential protective effect.

Some key points to consider:

• Large-scale studies and meta-analyses have not found a causal link between statin use and increased dementia risk 1.
• Statins work by lowering cholesterol levels and reducing inflammation in blood vessels, potentially improving blood flow to the brain.
• If you experience cognitive symptoms while taking statins, it is essential to discuss them with your healthcare provider rather than stopping medication on your own, as the cardiovascular benefits of statins typically outweigh potential risks for those prescribed these medications.
• The 2024 study also noted that the addition of ezetimibe or PCSK9 inhibitors to statin therapy did not change cognitive function, even at very low LDL cholesterol levels 1.

Overall, the current evidence supports the use of statins in individuals with diabetes at high risk for ASCVD, without concern for increasing dementia risk 1.

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 FDA drug label does mention cognitive impairment associated with statin use, but it does not explicitly state that statins increase the risk of dementia. The answer to whether statins increase dementia risk is not directly addressed in the label. However, given the information about cognitive impairment, a conservative clinical decision would be to monitor patients for cognitive changes when prescribing statins. 2

From the Research

Statins and Dementia Risk

• The relationship between statin use and dementia risk is complex and has been studied in various research papers 3, 4.
• A study published in the Journal of Internal Medicine in 2015 found that statin use reduces the risk of dementia in elderly patients, with a significant inverse association between total or daily equivalent statin dosage and dementia risk 3.
• However, another study published in JAMA in 2022 did not specifically investigate the relationship between statin use and dementia risk, but rather focused on the benefits and harms of statins for reducing cardiovascular disease-related morbidity or mortality in adults without a history of known cardiovascular disease 4.
• Other studies have investigated the effects of omega-3 fatty acids on cognitive function and dementia risk, with some suggesting that omega-3 fatty acid supplementation may have beneficial effects on cognitive decline and dementia prevention 5, 6, 7.

Omega-3 Fatty Acids and Cognitive Function

• Research suggests that omega-3 fatty acids, particularly docosahexaenoic acid (DHA), may have beneficial effects on cognitive decline and dementia prevention 5.
• A systematic review and meta-analysis published in Medicine in 2018 found that combination therapy with statins and omega-3 fatty acids was more effective in reducing total cholesterol and triglycerides than statin monotherapy, but did not significantly differ in terms of low-density lipoprotein (LDL) cholesterol reduction 6.
• A randomized, double-blind, and placebo-controlled trial published in Clinical Therapeutics in 2018 found that adding omega-3 fatty acids to rosuvastatin in patients with residual hypertriglyceridemia despite statin treatment resulted in a greater reduction of triglycerides and non-HDL-C than rosuvastatin alone 7.

Conclusion Not Provided

As per the instructions, no conclusion will be provided. The information presented is based on the available research papers and is intended to provide an overview of the relationship between statin use and dementia risk, as well as the effects of omega-3 fatty acids on cognitive function.