Statins

While statins have been examined for their effects on dementia risk since 2000, the evidence shows little to no direct impact. Our search identified:

• 1 meta-analysis of 2 randomized controlled trials in Alzheimer's patients
• Multiple meta-analyses and systematic reviews on observational studies for dementia risk
• 1 observational study in Alzheimer's patients
• Numerous preclinical studies that established a biological rationale for benefit

The use of statins in late life is unlikely to reduce the risk of dementia. Although some meta-analyses of observational studies suggest that statins may lower the risk of dementia, they are based on studies with varied design and a high risk of unintentional biases [1][2]. An Alzrisk.org systematic review funded by the Alzheimer's Drug Discovery Foundation concluded that statin use late in life is unlikely to prevent cognitive decline or reduce dementia risk [3]. In addition, a meta-analysis of two randomized controlled trials reported that statin use does not reduce the risk of dementia [4]. Some concerns have been raised that statins may cause acute cognitive impairment, but this risk appears to be rare, reversible, and may be due to the simultaneous use of other medications (e.g., diphenhydramine, tricyclic antidepressants, some antipsychotics) [5].

Although late life statin use is unlikely to prevent dementia, statins effectively manage cholesterol in most individuals and protect from cardiovascular disease [6]. Cardiovascular health in turn is a risk factor for cognitive decline and dementia [7], suggesting that lifelong management of cholesterol with statins may reduce the risk of cognitive decline and dementia.

APOE 4 Carriers:

APOE4 carriers: Evidence on statins' effects on brain health for APOE4 carriers is mixed. At least three observational studies reported that APOE genotype had no effect on the relationship between statin use and dementia [8-10]. Another study suggested that statin use might have a slightly stronger protective association for people who carry at least one APOE4 allele [11]. For more information on what the APOE4 gene allele means for your health, read our APOE4 information page.

For Dementia Patients

The evidence to date does not suggest that statins are an effective treatment for dementia patients. A meta-analysis of four randomized controlled trials (1,154 participants, ages 50 to 90) of Alzheimer's patients did not show a reduction in cognitive decline in response to atorvastatin or simvastatin treatment. One of the four studies reported cognitive benefits for patients with higher baseline cholesterol levels, higher baseline cognitive scores, and APOE4 alleles [12].

Multiple large and long-term clinical trials along with nearly 20 years of use have shown that statins are generally safe, with some caveats. According to the American Heart Association, there is a small chance that statins may increase the risk of type 2 diabetes, liver injury, reversible memory loss, and potential muscle damage. For most patients, however, statins’ heart-protective factors far outweigh the potential side effects. In fact, the American Heart Association’s new guidelines suggest that individuals with a heart attack or stroke risk of 7.5 percent or higher within the next 10 years would benefit from a statin regimen. Statins pose distinct risks to patients with specific types of acute liver disease. They can also react badly with acid reflux medication and high amounts of grapefruit juice. Concerns have also been raised that statins may cause acute memory impairment. However, the evidence to date suggests that this risk is rare, reversible, and may be due to concurrent medications (e.g., diphenhydramine, tricyclic antidepressants, some antipsychotics) [5].

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

Many different types of statins are available by prescription. Statin dosing in clinical trials for cholesterol-lowering indications have ranged from 20 to 80 mg/day orally. Statins are usually taken for an extended period of time, often many years or decades. Three statins—simvastatin, lovastatin, and atorvastatin—are the most likely to enter the brain.

More information can be found in this Mayo Clinic article.

Check for drug-drug and drug-supplement interactions on Drugs.com.

1. Song Y, Nie H, Xu Y et al. (2013) Association of statin use with risk of dementia: a meta-analysis of prospective cohort studies. Geriatrics & gerontology international 13, 817-824.
2. Wong WB, Lin VW, Boudreau D et al. (2013) Statins in the prevention of dementia and Alzheimer's disease: a meta-analysis of observational studies and an assessment of confounding. Pharmacoepidemiology and drug safety 22, 345-358.
3. Power MC, Weuve J, Sharrett AR et al. (2015) Statins, cognition, and dementia-systematic review and methodological commentary. Nat Rev Neurol 11, 220-229.
4. McGuinness B, Craig D, Bullock R et al. (2016) Statins for the prevention of dementia. The Cochrane database of systematic reviews, CD003160.
5. Gauthier JM, Massicotte A (2015) Statins and their effect on cognition: Let's clear up the confusion. Can Pharm J (Ott) 148, 150-155.
6. Teng M, Lin L, Zhao YJ et al. (2015) Statins for Primary Prevention of Cardiovascular Disease in Elderly Patients: Systematic Review and Meta-Analysis. Drugs & aging 32, 649-661.
7. World Alzheimer's Report 2015 (PDF) (accessed 09/14 2015).
8. Dufouil C, Richard F, Fievet N et al. (2005) APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: the Three-City Study. Neurology 64, 1531-1538.
9. Li G, Shofer JB, Rhew IC et al. (2010) Age-varying association between statin use and incident Alzheimer's disease. Journal of the American Geriatrics Society 58, 1311-1317.
10. Sparks DL, Kryscio RJ, Sabbagh MN et al. (2008) Reduced risk of incident AD with elective statin use in a clinical trial cohort. Current Alzheimer research 5, 416-421.
11. Li G, Higdon R, Kukull WA et al. (2004) Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study. Neurology 63, 1624-1628.
12. McGuinness B, Craig D, Bullock R et al. (2014) Statins for the treatment of dementia. The Cochrane database of systematic reviews, CD007514.