STATINS AND COGNITIVE FUNCTIONS: ARE THERE ASSOCIATED DISORDERS OR PROTECTION FROM DEMENTIA?

Cover Page

Cite item

Full Text

Abstract

Background. Statins are widely used in clinical practice in cardiovascular disorders treatment. Along with this in 2012 Food and Drug Administration released a statement about rare cognitive disorders in some patients that were associated with statins use according to postmarketing reports. The decision was made to include mild and reversible cognitive side effects in product instructions. Alongside that active study of statins influence on cognitive functions for evaluation of clinical significance and risk factors of these adverse effects is going on. Objective. To present scientific literature review of statins influence on cognitive functions in different levels of evidence. Materials and methods. A literature search for foreign publications was performed in international search systems (PubMed and others) from year 1999 in order to write the review. The review is based on analysis of large observational and randomized clinical studies (RCS) as well as several metaanalyses of statins influence on cognitive function evaluation. Results. Since year 2000 publications on series of cases on neurocognitive disorders development after statin use have emerged. The disorders were presented mostly by transient or short amnesia or also by other symptoms (depression, joylessness, despair, aggression, anxiety, psychic tension, irritability, increased emotional reactivity, loss of interest in activities, in communication, or even suicide behavior). Cognitive disorders were observed after several months of treatment with statins of after dosage increase and were reversible after discontinuation of statins therapy. Further a number of retrospective case-control studies and prospective cohort studies of statins influence on cognitive function were performed. Most of them showed statins protective effect on dementia development in patients with Alzheimer disease and in patients with normal cognitive function. In some RCS taking account of cognitive functions as secondary outcomes no significant risk of cognitive function decrease or dementia development as well as no improvement in patients diagnosed with dementia after statins use were observed. Metaanalyses of observational studies and RCS did not also show negative impact of statins on cognitive function and dementia development. Conclusion. The present data supports the hypothesis that statins are partly related both with reversible cognitive side effects and with dementia risk decrease. More RCS are necessary for final decision on statins global impact on cognitive function and determination of individual risk factors.

About the authors

Marina V. Leonova

Interregional Public Organization “Russian Association of Clinical Pharmacologists”

Email: anti23@mail.ru
чл.-кор. РАЕН, д-р мед. наук, проф., клинический фармаколог

References

  1. Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 2005; 45: 89-118.
  2. FDA Drug Safety Communication: important safety label changes to cholesterol-lowering statin drugs [article online], 2012. http://www.fda.goV/Drugs/DrugSafety/ucm293101.htm#hcp
  3. Benarroch EE. Brain cholesterol metabolism and neurologic disease. Neurology 2008; 71: 136873.
  4. Shepardson NE, Shankar GM, Selkoe DJ. Cholesterol level and statin use in Alzheimer disease: I. Review of epidemiological and preclinical studies. Arch Neurol 2011; 68: 1239-44.
  5. 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: 871-80.
  6. Evans MA, Golomb BA. Statin-associated adverse cognitive effects: survey results from 171 patients. Pharmacotherapy 2009; 29 (7): 800-11.
  7. Sahebzamani FM, Munro CL, Marroquin OC et al. Examination of the FDA warning for statins and cognitive dysfunction. J Pharmacovigilance 2014; 2 (4): 141. doi: 10.4172/2329-6887.10001418
  8. Cham S, Koslik HJ, Golomb BA. Mood, personality, and behavior changes during treatment with statins: a case series. Drug Saf Case Rep 2016; 3 (1): 1.
  9. Bitzur R. Remembering Statins: Do statins have adverse cognitive effects? Diabetes Care 2016; 39 (Suppl. 2): S253-9.
  10. Jick H, Zornberg GL, Jick SS et al. Statins and the risk of dementia. Lancet 2000; 356: 1627-31.
  11. Hajjar I, Schumpert J, Hirth V et al. 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: M414-8.
  12. Rockwood K, Kirkland S, Hogan DB et al. Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch Neurol 2002; 59: 223-7.
  13. Yaffe K, Barrett-Connor E, Lin F, Grady D. Serum lipoprotein levels, statin use, and cognitive function in older women. Arch Neurol 2002; 59: 378-84.
  14. Wolozin B, Wang SW, Li NC et al. Simvastatin is associated with a reduced incidence of dementia and Parkinson’s disease. BMC Med 2007; 5: 20.
  15. Cramer C, Haan MN, Galea S et al. Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology 2008; 71: 344-50.
  16. Haag MD, Hofman A, Koudstaal PJ et al. Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study. J Neurol Neurosurg Psychiatry 2009; 80: 13-7.
  17. Wu CK, Yang YH, Lin TT et al. Statin use reduces the risk of dementia in elderly patients: a nationwide data survey and propensity analysis. J Intern Med 2015; 277: 343-52.
  18. Glasser SP, Wadley V, Judd S 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: 280-8.
  19. Benito-Leon J, Louis ED, Vega S, Bermejo-Pareja F Statins and cognitive functioning in the elderly: a population-based study. J Alzheimers Dis 2010; 21: 95-102.
  20. Rea TD, Breitner JC, Psaty BM et al. Statin use and the risk of incident dementia: the Cardiovascular Health Study. Arch Neurol 2005; 62: 1047-51.
  21. Steenland K, Zhao L, Goldstein FC, Levey AI. Statins and cognitive decline in older adults with normal cognition or mild cognitive impairment. J Am Geriatr Soc 2013; 61: 1449-55. ИНФОРМАЦИЯ ОБ АВТОРЕ / INFORMATION ABOUT THE AUTHOR
  22. Agostini JV, Tinetti ME, Han L et al. Effects of statin use on muscle strength, cognition, and depressive symptoms in older adults. J Am Geriatr Soc 2007; 55: 420-5.
  23. Lilly SM, Mortensen EM, Frei CR et al. Comparison of the risk of psychological and cognitive disorders between persistent and nonpersistent statin users. Am J Cardiol 2014; 114: 1035-9.
  24. Strom BL, Schinnar R, Karlawish J et al. Statin therapy and risk of acute memory impairment. JAMA Intern Med 2015; 175: 1399-405.
  25. Redelmeier DA, Manzoor F, Thiruchelvam D. Association between statin use and risk of dementia after a concussion. JAMA Neurol 2019. doi: 10.1001/jamaneurol.2019.1148
  26. Collins R, Armitage J, Parish S et al. Heart Protection Study Collaborative Group. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet 2004; 363: 757-67.
  27. Trompet S, van Vliet P, de Craen AJ et al. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J Neurol 2010; 257: 85-90.
  28. Bosch J, O’Donnell M, Swaminathan B et al. Effects of blood pressure and lipid lowering on cognition. Results from the HOPE-3 study. Neurology 2019; 92: e1-e12.
  29. A Clinical Trial of STAtin Therapy for Reducing Events in the Elderly (STAREE). ClinicalTrials.gov Identifier: NCT02099123.
  30. Richardson K, Schoen M, French B et al. Statins and cognitive function: a systematic review. Ann Intern Med 2013; 159: 688-97.
  31. Swiger KJ, Manalac RJ, Blumenthal RS et al. Statins and cognition: a systematic review and metaanalysis of short- and long-term cognitive effects. Mayo Clin Proc 2013; 88: 1213-21.
  32. Ott BR, Daiello LA, Dahabreh IJ et al. Do statins impair cognition? A systematic review and metaanalysis of randomized controlled trials. J Gen Intern Med 2015; 30: 348-58.
  33. McGuinness B, Craig D, Bullock R et al. Statins for the treatment of dementia. Cochrane Database Syst Rev 2014; 7: CD007514.
  34. McGuinness B, Craig D, Bullock R, Passmore P Statins for the prevention of dementia. Cochrane Database Syst Rev 2016; 1: CD003160.
  35. Zhang X, Wen J, Zhang Z. Statins use and risk of dementia: a dose-response meta-analysis. Medicine 2018; 97 (30): e11304.
  36. Chatterjee S, Krishnamoorthy P, Ranjan P et al. Statins and cognitive function: an updated review. Curr Cardiol Rep 2015; 17: 4.
  37. Schultz BG, Patten DK, Berlau DJ. The role of statins in both cognitive impairment and protection against dementia: a tale of two mechanisms. Transl Neurodegener 2018; 7: 5.

Copyright (c) 2019 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies