Ischemic heart disease remains the leading cause of death in the USA. Statins have substantially contributed to the decline in mortality due to heart disease. Historically, statins are hypothesized to be neuroprotective and beneficial in dementia, but recent reports have suggested an association with transient cognitive decline. We have critically appraised the relationship between statins and cognitive function in this review. Most of the data are observational and reported a protective effect of statins on dementia and Alzheimer’s disease in patients with normal cognition at baseline. Few studies, including two randomized control trials, were unable to find a statistically significant decrease in the risk or improvement in patients with established dementia or decline in cognitive function with statin use. As more randomized control trials are required to definitively settle this, cardiovascular benefits of statins must be weighed against the risks of cognitive decline on an individual basis.
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Bersot TP. Drug therapy for hypercholesterolemia and dyslipidemia. In: Brunton LL, Chabner BA, Knollmann BC, editors. Goodman and Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill; 2011.
Malloy MJ, Kane JP. Agents used in dyslipidemia. In: Katzung BG, Masters SB, Trevor AJ, editors. Basic and Clinical Pharmacology. 12th ed. New York: McGraw-Hill; 2012.
Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med. 2002;346(7):539–40.
Stone NJ, Robinson J, Lichtenstein AH, Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Nov 12. No abstract available.
Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto Jr AM, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.
Rajpathak SN, Kumbhani DJ, Alderman M, Crandall J, Barzilai N, Ridker PM. Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care. 2009;32(10):1924–9.
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 25 Mar 2014.
Swiger KJ, Manalac RJ, Blumenthal RS, Blaha MJ, Martin SS. Statins and cognition: a systematic review and meta-analysis of short and long term cognitive effects. Mayo Clin Proc. 2013;88(11):1213–21. This recent meta-analysis studied the effects of statin on short and long-term cognitive effects. The authors concluded that short-term use of statins is compatible with no adverse effect on cognition in patients without baseline cognitive dysfunction and long term use may support a beneficial role in prevention of dementia.
Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM. Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy. 2003;23(7):871–80.
MRC/BHF Heart Protection. Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial. Heart Protection Study Collaborative Group. Lancet. 2002;360(9326):7–22.
Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet. 2000;356:1627–31.
Rockwood K, Kirkland S, Hogan DB, MacKnight C, Merry H, Verreault R, et al. Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch Neurol. 2002;59(2):223–7.
Rodriguez EG, Dodge HH, Birzescu MA, Stoehr GP, Ganguli M. Use of lipid-lowering drugs in older adults with and without dementia: a community-based epidemiological study. J Am Geriatr Soc. 2002;50(11):1852–6.
Bernick C, Katz R, Smith NL, Rapp S, Bhadelia R, Carlson M, et al. Statins and cognitive function in the elderly: the Cardiovascular Health Study. Neurology. 2005;65(9):1388–94.
Wolozin B, Wang SW, Li NC, Lee A, Lee TA, Kazis LE. Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease. BMC Med. 2007;5:20.
Parikh NM, Morgan RO, Kunik ME, Chen H, Aparasu RR, Yadav RK, et al. Risk factors for dementia in patients over 65 with diabetes. Int J Geriatr Psychiatry. 2011;26:749–57.
Beydoun MA, Beason-Held LL, Kitner-Triolo MH, Beydoun HA, Ferrucci L, Resnick SM, et al. Statins and serum cholesterol's associations with incident dementia and mild cognitive impairment. J Epidemiol Community Health. 2011;65(11):949–57.
Elias PK, Elias MF, D'Agostino RB, Sullivan LM, Wolf PA. Serum cholesterol and cognitive performance in the Framingham Heart Study. Psychosom Med. 2005;67(1):24–30.
Ancelin ML, Carrière I, Barberger-Gateau P, Auriacombe S, Rouaud O, Fourlanos S, et al. Lipid lowering agents, cognitive decline, and dementia: the three-city study. J Alzheimers Dis. 2012;30(3):629–37.
Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, et al. Prospective study of pravastatin in the elderly at risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomized controlled trial. Lancet. 2002;360(9346):1623–30.
Richardson K, Schoen M, French B, Umscheid CA, Mitchell MD, Arnold SE, et al. Statins and cognitive function: a systematic review. Ann Intern Med. 2013;159(10):688–97. This is a recent systematic review of 57 studies in total including randomized control trials, cohort studies, case–control studies and cross-sectional studies analyzing the cognitive effect of statins. The review identified low-to-moderate quality evidence suggesting a neutral effect of statin on cognitive functions and there by recognizing the need for larger and better designed studies.
Green RC, McNagny SE, Jayakumar P, Cupples LA, Benke K, Farrer LA, et al. Statin use and the risk of Alzheimer's disease: the MIRAGE study. Alzheimers Dement. 2006;2:96–103.
Wolozin B, Kellman W, Ruosseau P, Celesia GG, Siegel G. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol. 2000;57(10):1439–43.
Bettermann K, Arnold AM, Williamson J, Rapp S, Sink K, Toole JF, et al. Statins, risk of dementia, and cognitive function: secondary analysis of the Ginkgo Evaluation of Memory Study. J Stroke Cerebrovasc Dis. 2012;21(6):436–44.
Sparks DL, Kryscio RJ, Sabbagh MN, Connor DJ, Sparks LM, Liebsack C. Reduced risk of incident AD with elective statin use in a clinical trial cohort. Curr Alzheimer Res. 2008;5(4):416–21.
Feldman HH, Doody RS, Kivipelto M, Sparks DL, Waters DD, Jones RW, et al. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease. LEADe. Neurology. 2010;74(12):956–64.
Sano M, Bell KL, Galasko D, Galvin JE, Thomas RG, van Dyck CH, et al. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology. 2011;77(6):556–63. This is a randomized placebo control trial of simvastatin on prevention of dementia with 18 months follow up period. It was found that simvastatin treatment had no effect on progression of symptoms in patients with mild to moderate Alzheimer’s dementia.
Schaefer EJ. Correspondence. Letters to the Editor in Grundy SM. HMG-CoA reductase inhibitors for hypercholesterolemia. N Engl J Med. 1998;319:24–33.
Kostis JB, Rosen RC, Wilson A. Central Nervous system effects of HMG CoA reductase inhibitors: Lovastatin and pravastatin on sleep and cognitive performance in patients with hypercholesterolemia. J Clin Pharmacol. 1994;34:989–96.
Yaffe K, Barrett-Connor E, Lin F, Grady D. Serum lipoprotein levels, statin use, and cognitive function in older women. Arch Neurol. 2002;59(3):378–84.
Cramer C, Haan MN, Galea S, Langa KM, Kalbfleisch JD. Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology. 2008;71(5):344–50.
Carlsson CM, Nondahl DM, Klein BE, McBride PE, Sager MA, Schubert CR, et al. Increased atherogenic lipoproteins are associated with cognitive impairment: effects of statins and subclinical atherosclerosis. Alzheimer Dis Assoc Disord. 2009;23:11–7.
Glasser SP, Wadley V, Judd S, Kana B, Prince V, Jenny N, et al. 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(5):280–8.
Roth T, Richardson GR, Sullivan JP, Lee RM, Merlotti L, Roehrs T. Comparative effects of pravastatin and lovastatin on nighttime sleep and daytime performance. Clin Cardiol. 1992;15(6):426–32.
Muldoon MF, Barger SD, Ryan CM, et al. Effects of lovastatin on cognitive function and psychological well-being. Am J Med. 2000;108(7):538–46.
Muldoon MF, Ryan CM, Sereika SM, Flory JD, Manuck SB. Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults. Am J Med. 2004;117(11):823–9.
Arvanitakis Z, Schneider JA, Wilson RS, Bienias JL, Kelly JF, Evans DA, et al. Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology. 2008;70:1795–802.
Benito-León J, Louis ED, Vega S, Bermejo-Pareja F. Statins and cognitive functioning in the elderly: a population-based study. J Alzheimers Dis. 2010;21(1):95–102.
Starr JM, McGurn B, Whiteman M, Pattie A, Whalley LJ, Deary IJ. Life long changes in cognitive ability are associated with prescribed medications in old age. Int J Geriatr Psychiatry. 2004;19(4):327–32.
Rosenberg PB, Mielke MM, Tschanz J, Cook L, Corcoran C, Hayden KM, et al. Effects of cardiovascular medications on rate of functional decline in Alzheimer disease. Am J Geriatr Psychiatry. 2008;16(11):883–92.
Ellul J, Archer N, Foy CM, Poppe M, Boothby H, Nicholas H, et al. The effects of commonly prescribed drugs in patients with Alzheimer’s disease on the rate of deterioration. J Neurol Neurosurg Psychiatry. 2007;78(3):233–9.
Haslinger-Löffler B. Multiple effects of HMG-CoA reductase inhibitors (statins) besides their lipid-lowering function. Kidney Int. 2008;74(5):553–5.
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Conflict of Interest
Saurav Chatterjee, Parasuram Krishnamoorthy, Pragya Ranjan, Ahana Roy, Anasua Chakraborty, Manpreet Singh Sabharwal, Richard Ro, Vikram Agarwal, Partha Sardar, Jacqueline Danik, Jay S Giri, Emil M DeGoma, and Dharam J Kumbhani declare that they have no conflict of interest.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
This article is part of the Topical Collection on Ischemic Heart Disease
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Chatterjee, S., Krishnamoorthy, P., Ranjan, P. et al. Statins and Cognitive Function: an Updated Review. Curr Cardiol Rep 17, 4 (2015). https://doi.org/10.1007/s11886-014-0559-3
- Statin use
- Cognitive function
- Alzheimer’s disease