Skip to main content

Advertisement

Log in

Effects of atorvastatin on higher functions

  • Clinical Trials
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

This study was undertaken to assess the effects of atorvastatin on cognition and higher mental functions.

Methods

In this before and after comparison study with controls, group one included 55 subjects aged ≥40 years requiring statins for cardiovascular indications who were started on atorvastatin (10 mg/day). Group two assigned to receive placebo were men and women chosen from the same geographical area and matched for age, sex, education and presence of hypertension and diabetes mellitus. Assessment was done with the Mini-Mental State Examination, Digit Span, Picture Test (average and delayed), Trail Making Test, Controlled Oral Word Association Test, Digit Symbol Substitution Test and Auditory Vigilance and Digit Vigilance Test at baseline and after 6 months. Changes between baseline and 6 months in the above parameters of mental function were compared using suitable statistical tests in the atorvastatin and placebo groups. To limit experiment-wise error, performance scores were grouped into five cognitive domains, which were labeled as attention, psychomotor speed, mental flexibility, working memory and memory retrieval. Summary effect sizes were estimated as z-scores.

Results

Both subjects on atorvastatin and placebo showed improvement in the majority of scales consistent with a learning effect on test performance. However, subjects treated with atorvastatin scored significantly over the placebo group in all domains, i.e. tests of attention [z-score=0.54, 95% confidence interval (CI): 0.38–0.64, p=0.001], psychomotor speed (z-score=0.28, 95% CI: O.09–0.47, p<0.001), mental flexibility (z-score=0.27, 95% CI: 0.22–0.32, p=0.01), working memory (z-score=1.22, 95% CI: 0.93–1.50, p<0.001) and memory retrieval (z-score=0.59, 95% CI: 0.36–0.82, p<0.05).

Conclusion

The present study concludes that there are significant beneficial effects of atorvastatin in a dose of 10 mg/day for a period of 6 months on higher functions as measured by the above standard neurocognitive tests.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Beatrice A, Golomb MH (2004) Conceptual foundations of UCSD Statin Study. Arch Int Med 164:153–162

    Article  Google Scholar 

  2. Benton D (1995) Do cholesterol levels slow mental processing? Psychosom Med 57:50–53

    PubMed  CAS  Google Scholar 

  3. Cattin L, Bordin P, Fonda M et al (1997) Factors associated with cognitive impairment among older Italian inpatients. J Am Geriatr Soc 45:1324–1330

    PubMed  CAS  Google Scholar 

  4. Cutler N, Sramek J, Veroff A, Block G, Stauffer L, Lines C (1995) Effects of treatment with simvastatin and pravastatin on cognitive function in patients with hypercholesterolemia. Br J Clin Pharmacol 39:333–336

    PubMed  CAS  Google Scholar 

  5. Davidson MH (2001) Safety profiles for the HMG Co-A reductase inhibitors: treatment and trust. Drugs 61:197–206

    Article  PubMed  CAS  Google Scholar 

  6. Dales MJM (2000) Statination. Intern Med News 1:55–56

    Google Scholar 

  7. Dietschy JM, Turley SD (2001) Cholesterol metabolism in the brain. Curr Opin Lipidol 12:105–112

    Article  PubMed  CAS  Google Scholar 

  8. England JD, Viles A, Walsh JC, Stewart PM (1999) Muscle side effects associated with simvastatin therapy. Med J Aust 153:562–563

    Google Scholar 

  9. Fassbender K, Simons M, Bergmann C, Stroick M et al (2001) Simvastatin strongly reduces levels of Alzheimer’s disease beta-amyloid peptides Abeta42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci USA 98:5856–5861

    Article  PubMed  CAS  Google Scholar 

  10. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    Article  PubMed  CAS  Google Scholar 

  11. Friedewald WT, Levy RI, Friedrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 18(6)499–502

    PubMed  CAS  Google Scholar 

  12. Golomb BA (1998) Cholesterol and violence: is there a connection? Ann Intern Med 128:478–487

    PubMed  CAS  Google Scholar 

  13. Grobbee ED, Bots LM (2003) Statin treatment and progression of atherosclerotic plaque burden. Drugs 63(9):893–911

    Article  PubMed  CAS  Google Scholar 

  14. Hajjar I, Schumpert J, Hirth V, Wieland D, Eleazer GP (2002) 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 57(7):M414–M418

    PubMed  Google Scholar 

  15. Harrison RWS, Ashton CH (1994) Do cholesterol-lowering agents affect brain activity? A comparison of simvastatin, pravastatin, and placebo in healthy volunteers. Br J Clin Pharmacol 37(3):231–236

    PubMed  CAS  Google Scholar 

  16. Houx PJ, Shepherd J, Blauw GJ et al (2002) Testing cognitive function in elderly populations: the PROSPER study. PROspective Study of Pravastatin in the Elderly at Risk. J Neurol Neurosurg Psychiatry 73(4):385–389

    Article  PubMed  CAS  Google Scholar 

  17. Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA (2000) Statins and the risk of dementia. Lancet 356(9242):1627–1631

    Article  PubMed  CAS  Google Scholar 

  18. King DS, Wilburn AJ, Wofford MR et al (2003) Cognitive impairment associated with atorvastatin and simvastatin. Pharmacotherapy 23(12):1663–1667

    Article  PubMed  Google Scholar 

  19. Kojro E, Gimpl G, Lammich S, Marz W, Fahrenholz F (2001) Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha-secretase ADAM10. Proc Natl Acad Sci USA 98:5815–5820

    Article  PubMed  CAS  Google Scholar 

  20. Krysiak R, Okopie B, Herman SZ (2003) Statin treatment and progression of atherosclerotic plaque burden. Drugs 63(9):893–911

    Article  PubMed  Google Scholar 

  21. Laufs U, Bohm M, Gertz K et al (2002) The hydrophilic HMG-CoA reductase inhibitor rosuvastatin regulates endothelial NO synthase and ischaemic stroke in vivo. Circulation 106(19 suppl):I272

    Google Scholar 

  22. Lewis RF, Rennick PM (1979) Manual for repeatable cognitive perceptual motor battery. Axon, Clinton, MI

    Google Scholar 

  23. Mason RP, Herbette LG, Silverman DI (1991) Can altering serum cholesterol affect neurologic functions? J Mol Cell Cardiol 23:1339–1342

    Article  PubMed  CAS  Google Scholar 

  24. Muldoon MF, Barger SD, Ryan CM et al (2000) Effects of lovastatin on cognitive function and psychological well-being. Am J Med 108:538–546

    Article  PubMed  CAS  Google Scholar 

  25. Muldoon MF, Flory JD, Ryan CM (2000) Serum cholesterol, the brain and cognitive functioning. In: Waldstein SR, Elias MF (eds) Neuropsychology of cardiovascular disease. Lawrence Erlbaum Associates, Mahwah, NJ

    Google Scholar 

  26. Nangle MR, Cotter MA, Cameron NE (2003) Effects of rosuvastatin on nitric oxide-dependent function in aorta and corpora cavernosum of diabetic mice: relationship to cholesterol biosynthesis pathway inhibition and lipid lowering. Diabetes 52(9):2396–2402

    Article  PubMed  Google Scholar 

  27. Orsi A, Sherman O, Woldeselassie Z (2001) Simvastatin-associated memory loss. Pharmacotherapy 21(6):767–769

    Article  PubMed  CAS  Google Scholar 

  28. Raggat JL, Partridge CN (2002) HMG CoA reductase inhibitors as immunomodulators: potential use in transplant rejection. Drugs 62(15):2185–2191

    Article  PubMed  Google Scholar 

  29. Reitan RM, Wolfson D (1993) The Halstead-Reitan neuropsychological test battery. Theory and clinical interpretation, 2nd edn. Neuropsychological Press, Tucson AZ

    Google Scholar 

  30. Rockwood K, Kirkland S, Hogan DB, MacKnight C, Merry H, Verreault R, Wolfson C (2002) Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly. Arch Neurol 59(2):223–227

    Article  PubMed  Google Scholar 

  31. Rose GA, Blackburn H, Gillum RF, Prineas RJ (1982) Cardiovascular survey methods, 2nd edn. (WHO Monograph Series no. 56 vol 1) WHO, Geneva

  32. Waldstein SR, Jennings, JR, Ryan CM et al (1996) Hypertension and neuropsychological performance in man: interactive effects of age. Health Psychol 15:102–109

    Article  PubMed  CAS  Google Scholar 

  33. Ryman A (1994) Cholesterol, violent death and mental disorder. BMJ 309:421–422

    PubMed  CAS  Google Scholar 

  34. Shepherd J, Blauw GJ, Murphy MB et al (2002) Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360:1623–1630

    Article  PubMed  CAS  Google Scholar 

  35. Simons M, Schwarzler F, Lutjohann D et al (2002) Treatment with simvastatin in normocholesterolemic patients with Alzheimer’s disease: a 26-week randomized, placebo-controlled, double-blind trial. Ann Neurol 52:346–350

    Article  PubMed  CAS  Google Scholar 

  36. Sparks DL, Connor DJ, Browne PJ et al (2002) HMG-CoA reductase inhibitors (statins) in the treatment of Alzheimer’s disease and why it would be ill-advised to use one that crosses the blood-brain barrier. J Nutr Health Aging 6:323–324

    Google Scholar 

  37. Spreen O, Strauss E (1991) A compendium of neuropsychological tests. Administration, norms, and commentary. Oxford University Press, New York

    Google Scholar 

  38. Stalker TJ, Lefer AM, Scalia R (2001) A new HMG-CoA reductase inhibitor, rosuvastatin, exerts anti-inflammatory effects on the microvasculature endothelium: the role of mevalonic acid. Br J Pharmacol 133(3):406–412

    Article  PubMed  CAS  Google Scholar 

  39. Wagstaff LR, Mitton MW, Arvik BM et al (2003) Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy 23(7):871–880

    Article  PubMed  Google Scholar 

  40. Wechsler D (1997) Wechsler Adult Intelligence Scale, 3rd edn. Psychological Corporation, San Antonio, TX

    Google Scholar 

  41. Wehr H, Parnowski T, Puzynski S et al (1996) Apolipoprotein E genotype and lipid and lipoprotein levels in dementia. Age Ageing 15:267–270

    Google Scholar 

  42. Wolozin B, Kellman W, Rousseau P, Celesia GG, Siegel G (2000) Decreased prevalence of Alzheimer disease associated with 3–hydroxy–3–methylglutaryl coenzyme A reductase inhibitors. Arch Neurol 57:1439–1443

    Article  PubMed  CAS  Google Scholar 

  43. Yaffe K, Barrett–Connor E, Lin F, Grady D (2002) Serum lipoprotein levels, statin use, and cognitive function in older women. Arch Neurol 59(3):378–384

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to N. N. Baheti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Parale, G.P., Baheti, N.N., Kulkarni, P.M. et al. Effects of atorvastatin on higher functions. Eur J Clin Pharmacol 62, 259–265 (2006). https://doi.org/10.1007/s00228-005-0073-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-005-0073-z

Keywords

Navigation