Do 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) 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. The most recent and highest quality evidence, including a systematic review of the U.S. Food and Drug Administration’s postmarketing surveillance databases, randomized controlled trials, and cohort, case-control, and cross-sectional studies, found no adverse effect of statins on cognition 1. In fact, several large randomized trials of statin versus placebo, where specific cognitive tests were performed, showed no differences between statin and placebo groups 1. Additionally, the addition of ezetimibe or PCSK9 inhibitors to statin therapy, even at very low LDL cholesterol levels, did not affect cognitive function 1. The benefits of statins in preventing heart attacks and strokes, especially in individuals with diabetes at high risk for ASCVD, typically outweigh potential risks, and fear of cognitive decline should not be a barrier to statin use 1. Some patients may report experiencing memory problems or brain fog while taking statins, but this is not supported by large clinical studies, and the confusion may arise because both cardiovascular disease and dementia become more common with age, and people with cardiovascular risk factors often take statins. If you're concerned about cognitive effects while taking a statin, don't stop your medication without consulting your doctor, as they might consider trying a different statin, adjusting your dose, or evaluating for other causes of cognitive symptoms. Key points to consider include:

• No consistent link between statin use and increased dementia risk has been found in large clinical studies 1
• Statins are primarily prescribed to lower cholesterol and reduce cardiovascular risk
• The benefits of statins for preventing heart attacks and strokes typically outweigh potential risks, especially in those with established cardiovascular disease or significant risk factors 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) Rare postmarketing 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)

Statins and Dementia: There is no direct evidence in the provided drug labels that statins cause dementia. However, there have been rare reports of cognitive impairment associated with statin use, which is generally nonserious and reversible upon statin discontinuation 2 3.

• Key points:
  • Rare reports of cognitive impairment
  • Generally nonserious and reversible
  • Variable times to symptom onset and resolution
• Clinical decision: Given the rare and reversible nature of cognitive impairment, it is essential to weigh the benefits of statin therapy against the potential risks and monitor patients for any signs of cognitive impairment.

From the Research

Statins and Dementia

• The relationship between statin use and dementia is complex, with some studies suggesting a potential link between statin use and cognitive decline, while others indicate that statins may have a protective effect against dementia 4, 5, 6, 7.
• A 2023 study published in PloS one found that ongoing statin use was not associated with cognitive decline or dementia progression in older adults with mild-moderate Alzheimer's disease 4.
• A 2018 narrative review published in Translational neurodegeneration discussed the potential mechanisms by which statins could both cause cognitive impairment and protect against dementia, highlighting the need for further research to fully understand the effects of statins on cognition 5.
• A 2003 case report analysis published in Pharmacotherapy found that some patients experienced memory loss associated with statin use, although the evidence was conflicting and causality was not certain 6.
• A 2018 systematic review and meta-analysis published in Scientific reports found that statin use was associated with a reduced risk of all-caused dementia, Alzheimer's disease, and mild cognitive impairment, although the evidence was not consistent across all studies 7.

Statin Types and Dementia

• A 2022 study published in the European journal of clinical pharmacology compared the effects of different statins on cardiovascular disease and physical disability in older adults, but did not specifically examine the relationship between statin type and dementia risk 8.
• The 2018 systematic review and meta-analysis published in Scientific reports found that hydrophilic statins were associated with a reduced risk of all-caused dementia, while lipophilic statins were associated with a reduced risk of Alzheimer's disease 7.

Adverse Effects of Statins

• The 2023 study published in PloS one found that ongoing statin use was not associated with adverse events, including abnormal liver function tests or falls, in older adults with mild-moderate Alzheimer's disease 4.
• The 2003 case report analysis published in Pharmacotherapy found that some patients experienced cognitive adverse effects associated with statin use, although the evidence was conflicting and causality was not certain 6.