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Statins and dementia

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Abstract

The incidence and prevalence of dementia are increasing. Dementia is a major cause of disability. Alzheimer’s disease (AD) is the most common type of dementia. There are no good prevention or treatment options. Experimental animal and laboratory studies have suggested that cholesterol metabolism in the brain is important in the causal pathway for dementia, possibly by modifying amyloid metabolism. A few studies have showed a possible relationship between mid-life blood cholesterol levels and risk of dementia, including AD. Case-control studies report that patients with AD were less likely to use lipid-lowering drugs, especially statins. Longitudinal epidemiology studies have not demonstrated a decreased risk of AD among statin users versus nonusers. Two clinical trials of statin therapy to reduce cardiovascular disease have not shown any reduction in risk of cognitive decline or dementia. The results of two secondary prevention trials will be reported shortly. In spite of negative studies, the possibility remains that statin therapy may reduce risk of dementia and AD. Primary prevention trials are difficult and expensive and will likely not be done in the United States.

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References and Recommended Reading

  1. DeKosky ST: Statin therapy in the treatment of Alzheimer disease; what is the rationale? Am J Med 2005, 118:48S–53S.

    Article  CAS  Google Scholar 

  2. Foldi MA, Belgeri MT: HMG-CoA reductase inhibitors for the prevention of Alzheimer’s disease. Clin Geriatr 2005, 13:35–44.

    Google Scholar 

  3. Blennow K, de Leon MJ, Zetterberg H: Alzheimer’s disease. Lancet 2006, 368:387–403.

    Article  PubMed  CAS  Google Scholar 

  4. Reiss AB: Cholesterol and apolipoprotein E in Alzheimer’s disease. Am J Alzheimers Dis Other Dement 2005, 20:91–96.

    Article  Google Scholar 

  5. Wolozin B, Bednar MM: Interventions for heart disease and their effects on Alzheimer’s disease. Neurol Res 2006, 28:630–636.

    Article  PubMed  CAS  Google Scholar 

  6. Miida T, Takahashi A, Tanabe N, Ikeuchi T: Can statin therapy really reduce the risk of Alzheimer’s disease and slow its progression? Curr Opin Lipidol 2005, 16:619–623.

    Article  PubMed  CAS  Google Scholar 

  7. Kuller LH, Lopez OL, Jagust WJ, et al.: Determinants of vascular dementia in the Cardiovascular Health Study. Neurology 2005, 64:1548–1552.

    Article  PubMed  CAS  Google Scholar 

  8. Leys D, Henon H, Mackowiak-Cordoliani MA, et al.: Poststroke dementia. Lancet Neurol 2005, 4:752–759.

    Article  PubMed  Google Scholar 

  9. White L, Petrovitch H, Hardman J, et al.: Cerebrovascular pathology and dementia in autopsied Honolulu-Asia Aging Study participants. In Alzheimer’s Disease. Vascular Etiology and Pathology. Edited by de la Torre JC, Kalaria R, Nakajima K, et al. Ann NY Acad Sci 2002, 977:9–23.

  10. Corder EH, Saunders AM, Strittmatter WJ, et al.: Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 1993, 261:921–923.

    Article  PubMed  CAS  Google Scholar 

  11. Wolozin B: Cholesterol, statins and dementia. Curr Opin Lipidol 2004, 15:667–672.

    Article  PubMed  CAS  Google Scholar 

  12. Shobab LA, Hsiung GY, Feldman HH: Cholesterol in Alzheimer’s disease. Lancet Neurol 2005, 4:841–852.

    Article  PubMed  CAS  Google Scholar 

  13. Ladu MJ, Reardon C, van Eldik L, et al.: Lipoproteins in the central nervous system. Ann NY Acad Sci 2000, 903:167–175.

    Article  PubMed  CAS  Google Scholar 

  14. Sparks DL, Scheff SW, Hunsaker JC, et al.: Induction of Alzheimer-like beta-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol. Exp Neurol 1994, 126:88–94.

    Article  PubMed  CAS  Google Scholar 

  15. Schmechel D, Sullivan, Mace B, et al.: High saturated fat diets are associated with Abeta deposition in primates (Abstract #1202). Neurobiol Aging 2002, 23:S1–S606.

    Article  Google Scholar 

  16. Hyman BT, Strickland D, Rebeck GW: Role of the low-density lipoprotein receptor-related protein beta-amyloid metabolism and Alzheimer disease. Arch Neurol 2000, 57:646–650.

    Article  PubMed  CAS  Google Scholar 

  17. Newman AB, Fitzpatrick AL, Lopez O, et al.: Dementia and Alzheimer’s disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort. J Am Geriatr Soc 2005, 53:1101–1107.

    Article  PubMed  Google Scholar 

  18. Hendrie HC, Murrell J, Gao S, et al.: International studies in dementia with particular emphasis on populations of African origin. Alzheimer Dis Assoc Disord 2006, 20:S42–S46.

    Article  PubMed  Google Scholar 

  19. Chandra V, Pandav R, Dodge HH, et al.: Incidence of Alzheimer’s disease in a rural community in India: the Indo-US study. Neurology 2001, 57:985–989.

    PubMed  CAS  Google Scholar 

  20. Kivipelto M, Helkala EL, Laasko MP, et al.: Apolipoprotein E4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann Intern Med 2002, 137:149–155.

    PubMed  CAS  Google Scholar 

  21. Jarvik GP, Wijsman EM, Kukull WA, et al.: Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer’s disease: a case-control study. Neurology 1995, 45:1092–1096.

    PubMed  CAS  Google Scholar 

  22. Luchsinger JA, Tang MX, Shea S, Mayeux R: Caloric intake and the risk of Alzheimer disease. Arch Neurol 2002, 59:1258–1263.

    Article  PubMed  Google Scholar 

  23. Bjorkhem I, Lutjohann D, Diczfalusy U, et al.: Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. Proc Natl Acad Sci U S A 1996, 93:9799–9804.

    Article  PubMed  Google Scholar 

  24. Mahley RW, Huang Y: Apolipoprotein E: from atherosclerosis to Alzheimer’s disease and beyond. Curr Opin Lipidol 1999, 10:207–217.

    Article  PubMed  CAS  Google Scholar 

  25. Bjorkhem I, Andersson U, Ellis E, et al.: From brain to bile. Evidence that conjugation and beta-hydroxylation are important for elimination of 24S-hydroxycholesterol (cere-brosterol) in humans. J Biol Chem 2001, 276:37004–37010.

    Article  PubMed  CAS  Google Scholar 

  26. Meaney S, Lutjohann D, Diczfalusy U, Bjorkhem I: Formation of oxysterols from different pools of cholesterol as studied by stable isotope technique: cerebral origin of most circulating 24S-hydroxycholesterol in rats, but not in mice. Biochim Biophys Acta 2000, 1486:293–298.

    PubMed  CAS  Google Scholar 

  27. Bjorkhem I, Lutjohann D, Breuer O, et al.: Importance of a novel oxidative mechanism for elimination of brain cholesterol. Turnover of cholesterol and 24(S)-hydroxycholesterol in rat brain as measured with 18O2 techniques in vivo and in vitro. J Biol Chem 1997, 272:30178–30184.

    Article  PubMed  CAS  Google Scholar 

  28. Leoni V, Masterman T, Patel P, et al.: Side chain oxidized oxysterols in cerebrospinal fluid and the integrity of blood-brain and blood-cerebrospinal fluid barriers. J Lipid Res 2000, 41:195–198.

    Google Scholar 

  29. Lutjohann D, Papassotiropoulos A, Bjorkhem I, et al.: Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients. J Lipid Res 2000, 41:195–198.

    PubMed  CAS  Google Scholar 

  30. Jick H, Zornberg GL, Jick SS, et al.: Statins and the risk of dementia. Lancet 2000, 356:1627–1631.

    Article  PubMed  CAS  Google Scholar 

  31. 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, 59:223–227.

    Article  PubMed  Google Scholar 

  32. Wolozin B, Kellman W, Russeau P, et al.: Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000, 57:1439–1443.

    Article  PubMed  CAS  Google Scholar 

  33. Rodriguez EG, Dodge HH, Birzescu MA, et al.: 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.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  35. Dufouil C, Richard F, Fievet N, et al.: APOE genotype, cholesterol level, lipid-lowering treatment, and dementia. The Three-City Study. Neurology 2005, 64:1531–1538.

    Article  PubMed  CAS  Google Scholar 

  36. Zandi PP, Sparks L, Khachaturian AS, et al.: Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch Gen Psychiatry 2005, 62:217–224.

    Article  PubMed  CAS  Google Scholar 

  37. Li G, Higdon R, Kukull WA, et al.: Statin therapy and risk of dementia in the elderly. A community-based prospective cohort study. Neurology 2004, 63:1624–1628.

    PubMed  CAS  Google Scholar 

  38. Bernick C, Katz R, Smith NL, et al.: Statins and cognitive function in the elderly. The Cardiovascular Health Study. Neurology 2005, 65:1388–1394.

    Article  PubMed  CAS  Google Scholar 

  39. Rea TD, Breitner JC, Psaty BM, et al.: Statin use and the risk of incident dementia. The Cardiovascular Health Study. Arch Neurol 2005, 62:1047–1051.

    Article  PubMed  Google Scholar 

  40. Rockwood K: Epidemiological and clinical trials evidence about a preventive role for statins in Alzheimer’s disease. Acta Neurol Scand 2006, 114:71–77.

    Article  Google Scholar 

  41. Heart Protection Study Collaborative Group: MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet 2002, 360:7–22.

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  43. Sparks DL, Sabbagh MN, Connor DJ, et al.: Atorvastatin for the treatment of mild to moderate Alzheimer disease. Preliminary results. Arch Neurol 2005, 62:753–757.

    Article  PubMed  Google Scholar 

  44. Masse I, Bordet R, Deplanque D, et al.: Lipid lowering agents are associated with a slower cognitive decline in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2005, 76:1624–1629.

    Article  PubMed  CAS  Google Scholar 

  45. Scott HD, Laake K: Statins for the prevention of Alzheimer’s disease. Cochrane review and plain language summary. http://www.cochrane.org/reviews/en/ab003160.html Accessed May 30, 2006.

  46. Locatelli S, Lutjohann D, Schmidt HH, et al.: Reduction of plasma 24S-hydroxycolesterol (cerebrosterol) levels using high-dosage simvastatin in patients with hypercholesterolemia. Evidence that simvastatin affects cholesterol metabolism in the human brain. Arch Neurol 2002, 59:213–216.

    Article  PubMed  Google Scholar 

  47. Fassbender K, Stroick M, Bertsch T, et al.: Effects of statins on human cerebral cholesterol metabolism and secretion of Alzheimer amyloid peptide. Neurology 2002, 59:1257–1258.

    PubMed  CAS  Google Scholar 

  48. McKenney JM, Davidson MH, Jacobson TA, Guyton JR: Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol 2006, 97:89C–94C.

    Article  PubMed  CAS  Google Scholar 

  49. Golomb BA, Criqui MH, White HL, Dimsdale JE: The UCSD Statin Study: a randomized controlled trial assessing the impact of statins on selected noncardiac outcomes. Control Clin Trials 2004, 25:178–202.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Lewis H. Kuller MD, DrPH.

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Kuller, L.H. Statins and dementia. Curr Atheroscler Rep 9, 154–161 (2007). https://doi.org/10.1007/s11883-007-0012-9

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