Abstract
Objective
To evaluate the effect of statins on short-term cognitive function and the long-term
incidence of dementia.
Patients and Methods
A systematic search was performed of MEDLINE, EMBASE, and the Cochrane Central Register
from their inception to April 25, 2013. Adults with no history of cognitive dysfunction
treated with statins were included from high-quality randomized controlled trials
and prospective cohort studies after formal bias assessment.
Results
Sixteen studies were included in qualitative synthesis and 11 in quantitative synthesis.
Short-term trials did not show a consistent effect of statin therapy on cognitive
end points. Digit Symbol Substitution Testing (a well-validated measure of cognitive
function) was the most common short-term end point, with no significant differences
in the mean change from baseline to follow-up between the statin and placebo groups
(mean change, 1.65; 95% CI, –0.03 to 3.32; 296 total exposures in 3 trials). Long-term
cognition studies included 23,443 patients with a mean exposure duration of 3 to 24.9
years. Three studies found no association between statin use and incident dementia,
and 5 found a favorable effect. Pooled results revealed a 29% reduction in incident
dementia in statin-treated patients (hazard ratio, 0.71; 95% CI, 0.61-0.82).
Conclusion
In patients without baseline cognitive dysfunction, short-term data are most compatible
with no adverse effect of statins on cognition, and long-term data may support a beneficial
role for statins in the prevention of dementia.
Abbreviations and Acronyms:
FDA (Food and Drug Administration), DSST (Digit Symbol Substitution Test)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Mayo Clinic ProceedingsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
FDA Drug Safety Communication: important safety label changes to cholesterol-lowering statin drugs. US FDA website. http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm. Accessed August 15, 2013.
- Association between statin use and Alzheimer’s disease.Neuroepidemiology. 2004; 23: 94-98
- Do statins reduce risk of incident dementia and Alzheimer disease?.Arch Gen Psychiatry. 2005; 62: 217-224
- Statins, risk of dementia, and cognitive function: secondary analysis of the Ginkgo Evaluation of Memory study.J Stroke Cerebrovasc Dis. 2012; 21: 436-444
- Statins and serum cholesterol’s associations with incident dementia and mild cognitive impairment.J Epidemiol Community Health. 2011; 65: 949-957
- Statin-associated adverse cognitive effects: survey results from 171 patients.Pharmacotherapy. 2009; 29: 800-811
- Simvastatin-associated memory loss.Pharmacotherapy. 2001; 21: 767-769
- Statin-associated memory loss: analysis of 60 case reports and review of the literature.Pharmacotherapy. 2003; 23: 871-880
- Changes in memory function and neuronal activation associated with atorvastatin therapy.Pharmacotherapy. 2010; 30: 236e-240e
- Statins and cognitive functioning in the elderly: a population-based study.J Alzheimers Dis. 2010; 21: 95-102
- Effects of lovastatin on cognitive function and psychological well-being.Am J Med. 2000; 108: 538-546
- Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults.Am J Med. 2004; 117: 823-829
- Pravastatin and cognitive function in the elderly: results of the PROSPER study.J Neurol. 2010; 257: 85-90
- The controversies of statin therapy: weighing the evidence.J Am Coll Cardiol. 2012; 60: 875-881
- Statins for the primary prevention of cardiovascular disease.Cochrane Database Syst Rev. 2013; 1: CD004816
- Healthy men should not take statins.JAMA. 2012; 307: 1491-1492
Rosenberg M. Do you really need that statin? this expert says no. Huffpost Healthy Living: The Blog. The Huffington Post. http://www.huffingtonpost.com/martha-rosenberg/statins_b_1818370.html. Accessed August 15, 2013.
Parker-Pope T. A heart helper may come at a price for the brain. The Well Column. The New York Times. http://well.blogs.nytimes.com/2012/03/05/help-for-the-heart-comes-with-a-price-for-the-brain/?_r=0. Accessed August 15, 2013.
- Statins and the risk of dementia.Lancet. 2000; 356: 1627-1631
- Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors.Arch Neurol. 2000; 57: 1439-1443
- Statin use and the risk of incident dementia: the Cardiovascular Health Study.Arch Neurol. 2005; 62: 1047-1051
- MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.Lancet. 2002; 360: 7-22
- Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial.Lancet. 2002; 360: 1623-1630
- Use of lipid-lowering drugs in older adults with and without dementia: a community-based epidemiological study.J Am Geriatr Soc. 2002; 50: 1852-1856
- Prevention and treatment of dementia or Alzheimer’s disease by statins: a meta-analysis.Dement Geriatr Cogn Disord. 2007; 23: 194-201
- Statins in the prevention of dementia and Alzheimer’s disease: a meta-analysis of observational studies and an assessment of confounding.Pharmacoepidemiol Drug Saf. 2013; 22: 345-358
Song Y, Nie H, Xu Y, Zhang L, Wu Y. Association of statin use with risk of dementia: a meta-analysis of prospective cohort studies [published online ahead of print March 6, 2013]. Geriatr Gerontol Int. doi:10.1111/ggi.12044.
- Optimal search strategies for retrieving scientifically strong studies of treatment from Medline: analytical survey.BMJ. 2005; 330: 1179-1182
- Wechsler Adult Intelligence Scale.3rd ed. Psychological Corp, San Antonio, TX1997
Higgins J. Chapter 8: assessing risk of bias in included studies: Table 8.5 a. In: Cochrane Handbook for Systematic Reviews of Interventions. http://handbook.cochrane.org/. Accessed August 6, 2012.
Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm. Accessed August 15, 2013.
- Do cholesterol-lowering agents affect brain activity? a comparison of simvastatin, pravastatin, and placebo in healthy volunteers.Br J Clin Pharmacol. 1994; 37: 231-236
- Central nervous system effects of HMG CoA reductase inhibitors: lovastatin and pravastatin on sleep and cognitive performance in patients with hypercholesterolemia.J Clini Pharmacol. 1994; 34: 989-996
- Effects of treatment with simvastatin and pravastatin on cognitive function in patients with hypercholesterolaemia.Br J Clin Pharmacol. 1995; 39: 333-336
- Effects of treatment with lovastatin and pravastatin on daytime cognitive performance.Clin Cardiol. 1995; 18: 209-214
- Effects of atorvastatin on higher functions.Eur J Clin Pharmacol. 2006; 62: 259-265
- Effect of atorvastatin on cognitive function in patients from the Lipid Lowering and Onset of Renal Disease (LORD) trial.Pharmacotherapy. 2007; 27: 183-190
- Atovastatin, diabetic dyslipidemia, and cognitive functioning.Diabetes Care. 2002; 25: 1250-1251
- Effects of lovastatin and pravastatin on cognitive function in military aircrew.Aviat Space Environ Med. 2001; 72: 805-812
- Effect of pharmacologic lipid lowering on health-related quality of life in older persons: results from the Cholesterol Reduction in Seniors Program (CRISP) Pilot Study.J Am Geriatr Soc. 1997; 45: 8-14
- The association of statin use and statin type and cognitive performance: analysis of the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study.Clin Cardiol. 2010; 33: 280-288
- Effect of statins on a wide range of health outcomes: a cohort study validated by comparison with randomized trials.Br J Clin Pharmacol. 2009; 67: 99-109
- The impact of the use of statins on the prevalence of dementia and the progression of cognitive impairment.J Gerontol A Biol Sci Med Sci. 2002; 57: 414-418
- Serum lipoprotein levels, statin use, and cognitive function in older women.Arch Neurol. 2002; 59: 378-384
- Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people.Arch Neurol. 2002; 59: 223-227
- APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: the Three-City Study.Neurology. 2005; 64: 1531-1538
- Serum total cholesterol, statins and cognition in non-demented elderly.Neurobiol Aging. 2009; 30: 1006-1009
- Statins and cognitive function in the elderly: the Cardiovascular Health Study.Neurology. 2005; 65: 1388-1394
- Cholesterol and cognitive performance in normal controls and the influence of elective statin use after conversion to mild cognitive impairment: results in a clinical trial cohort.Neurodegener Dis. 2010; 7: 183-186
- Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study.Neurology. 2004; 63: 1624-1628
- Simvastatin is associated with a reduced incidence of dementia and Parkinson’s disease.BMC Med. 2007; 5: 20
- Age-varying association between statin use and incident Alzheimer’s disease.J Am Geriatr Soc. 2010; 58: 1311-1317
- Statins, incident Alzheimer disease, change in cognitive function, and neuropathology.Neurology. 2008; 70: 1795-1802
- Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study.Neurology. 2008; 71: 344-350
- Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity: the Rotterdam Study.J Neurol Neurosurg Psychiatry. 2009; 80: 13-17
- Association of statin use with cognitive decline in elderly African Americans.Neurology. 2007; 69: 1873-1880
- Reduced risk of incident AD with elective statin use in a clinical trial cohort.Curr Alzheimer Res. 2008; 5: 416-421
- Lipid lowering agents, cognitive decline, and dementia: the Three-City Study.J Alzheimers Dis. 2012; 30: 629-637
- Cardiovascular event reduction and adverse events among subjects attaining low-density lipoprotein cholesterol <50 mg/dl with rosuvastatin: the JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin).J Am Coll Cardiol. 2011; 57: 1666-1675
Article info
Publication history
Published online: October 03, 2013
Identification
Copyright
© 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
