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

Statins Do Not Increase Risk for Dementia

Current evidence does not support the concern that statins increase the risk of dementia; in fact, multiple high-quality guidelines and systematic reviews suggest statins may actually reduce dementia risk in some populations. 1, 2

Evidence Against Statin-Induced Cognitive Impairment

• The American Diabetes Association's Standards of Medical Care (2022) explicitly states that "fear of cognitive decline should not be a barrier to statin use in individuals with diabetes and a high risk for cardiovascular disease" 1
• Multiple large randomized trials with specific cognitive testing found no differences in cognitive function between statin and placebo groups 1, 2
• A systematic review by the U.S. Food and Drug Administration (FDA) examining postmarketing surveillance databases, randomized controlled trials, and observational studies concluded that published data do not reveal an adverse effect of statins on cognition 1
• The European Atherosclerosis Society Consensus Panel statement provides several lines of evidence against an association between statins and cognitive dysfunction 2
• Studies examining the addition of other lipid-lowering agents (ezetimibe or PCSK9 inhibitors) to statin therapy showed no change in cognitive function, even when treating to very low LDL cholesterol levels 1

FDA Labeling and Reported Cognitive Effects

• The FDA label for atorvastatin acknowledges "rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with the use of all statins" 3
• However, these cognitive symptoms are generally characterized as:
  • Nonserious
  • Reversible upon statin discontinuation
  • Variable in onset time (1 day to years)
  • Resolving within a median of 3 weeks after discontinuation 3

Evidence Suggesting Potential Protective Effects

• Some observational studies and meta-analyses have suggested statins may actually reduce the risk of dementia:
  • A meta-analysis of 25 studies found statin use was significantly associated with reduced risk of all-cause dementia (adjusted RR = 0.849), Alzheimer's disease (adjusted RR = 0.719), and mild cognitive impairment (adjusted RR = 0.737) 4
  • The Ginkgo Evaluation of Memory Study found that among participants without mild cognitive impairment at baseline, current statin use was associated with reduced risk of all-cause dementia (HR 0.79) and Alzheimer's disease (HR 0.57) 5

Management Approach for Patients with Cognitive Concerns

• If a patient reports cognitive symptoms while taking statins:
  • Evaluate for other potential causes of memory impairment, including other medications, systemic conditions, and neuropsychiatric causes 6
  • Document the specific nature of memory complaints to establish a baseline for monitoring 6
  • Consider temporarily discontinuing the statin for 2-4 weeks to see if symptoms improve 6
  • For high cardiovascular risk patients, prioritize statin therapy due to proven mortality benefits 6, 2
  • Consider rechallenging with a different statin, lower dose, or alternative dosing regimen if cardiovascular risk warrants continued therapy 6

Clinical Decision Making

• The decision to continue, modify, or discontinue statin therapy should balance cardiovascular risk reduction benefits against any impact of cognitive symptoms on quality of life 6
• For elderly patients (>75 years) with cognitive concerns, consider using moderate-intensity rather than high-intensity statins 6
• In patients with high cardiovascular risk who cannot tolerate statins due to cognitive effects, consider non-statin lipid-lowering therapies 6

Limitations of Current Evidence

• A Cochrane review noted that while observational studies suggested a protective effect of statins against dementia, randomized controlled trials have not confirmed this benefit 7
• Most studies focus on patients with vascular risk factors, so findings may not generalize to all populations 7

In conclusion, current evidence strongly indicates that statins do not increase dementia risk, and concerns about cognitive decline should not prevent appropriate statin therapy for cardiovascular risk reduction.