Is there a correlation between HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, commonly referred to as statins, and the development of dementia?

From the Guidelines

The current evidence suggests that statins do not increase the risk of dementia and may even have a protective effect, as indicated by the most recent study from 2024 1. The relationship between statins and dementia has been extensively studied, with multiple lines of evidence pointing against a potential adverse impact of lipid-lowering agents on cognitive function.

• Several large randomized trials of statin versus placebo have been conducted, with specific cognitive tests performed, and no differences were seen between statin and placebo 1.
• Additionally, no change in cognitive function has been reported in studies with the addition of ezetimibe or PCSK9 inhibitors to statin therapy, including among individuals treated to very low LDL cholesterol levels 1.
• 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 found that published data do not reveal an adverse effect of statins on cognition 1. Therefore, a concern that statins or other lipid-lowering agents might cause cognitive dysfunction or dementia is not currently supported by evidence and should not deter their use in individuals with diabetes at high risk for ASCVD 1. It is essential to note that statins are not currently prescribed specifically for dementia prevention, and their primary indication remains cardiovascular disease prevention.
• Some patients report memory issues when starting statins, but these complaints are generally mild and often resolve with continued use or medication adjustment.
• Anyone concerned about dementia risk should discuss comprehensive prevention strategies with their healthcare provider, as statins represent just one potential factor in a broader approach to brain health. The protective effect of statins on dementia seems to be strongest when started in midlife rather than late life, although more research is needed to confirm this association. Overall, the current evidence supports the use of statins in individuals with diabetes at high risk for ASCVD, without concern for adverse effects on cognitive function or 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 use of statins, including atorvastatin, has been associated with rare reports of cognitive impairment, which may include symptoms such as memory loss, forgetfulness, and confusion. However, these effects are generally nonserious and reversible upon discontinuation of the statin. There is no direct evidence in the drug label to suggest a correlation between statin use and dementia. 2

From the Research

Statins and Dementia Correlation

• The correlation between statins and dementia is a complex one, with various studies yielding different results.
• A study published in 2020 found that switching from low-dose simvastatin to high-dose atorvastatin in patients with type 2 diabetes resulted in a slight increase in HbA1c without causing cognitive decline 3.
• Another study from 2020 discovered that the combination of statins and antihypertensive therapy may reduce the risk of Alzheimer's disease and related dementias, particularly when using pravastatin or rosuvastatin with renin-angiotensin system-acting antihypertensives 4.
• A systematic review and meta-analysis published in 2018 found that the use of statins was associated with a reduced risk of all-caused dementia, Alzheimer's disease, and mild cognitive impairment, but not vascular dementia 5.
• The same review suggested that hydrophilic statins may be associated with a reduced risk of all-caused dementia, while lipophilic statins may be associated with a reduced risk of Alzheimer's disease 5.
• A 2022 review of statin therapy highlighted the efficacy and safety of statins in reducing atherosclerotic cardiovascular risk, but did not specifically address the correlation between statins and dementia 6.
• Patient beliefs and attitudes towards taking statins can also play a role in their effectiveness, with factors such as confidence in prevention, routinizing into daily life, and medical distrust influencing adherence to statin therapy 7.