Current Neurology and Neuroscience Reports

, Volume 2, Issue 5, pp 392–399 | Cite as

Prevention of Alzheimer’s disease: Where we stand

  • Mary Sano
Article

Abstract

Alzheimer’s disease has been recognized as a major public health issue that will grow in prominence as life expectancy increases and as the shape of population demographics shifts toward expansion in the older age ranges with contraction in younger ages. The magnitude of the problem can be expressed in incidence, prevalence economics, and quality of life. Great strides have been made in understanding and treating this disease, but current clinical management is far from satisfactory and progression seems inevitable once the disease is diagnosed. Such forces in any disease encourage intervention strategies to move from treatment to prevention. However, this vision can only be met with reasonable success when pathology is understood and there is evidence that manipulation of that pathology leads to clinical benefit. This is the challenge that lies ahead to achieve the goal of prevention of Alzheimer’s disease. This review begins by examining the progress that has been made in this disease. Current efforts to develop prevention strategies are described and possible agents for future evaluation are discussed.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Kawas C, Gray S, Brookmeyer R, Fozard J, Zonderman A: Age-specific incidence rates of Alzheimer’s disease: the Baltimore Longitudinal Study of Aging. Neurology 2000, 54:2072–2077. Important study.PubMedGoogle Scholar
  2. 2.
    Gao S, Hendrie HC, Hall KS, Hui S: The relationships between age, sex, and the incidence of dementia and Alzheimer disease: a meta-analysis. Arch Gen Psychiatry 1998, 55:809–815.PubMedCrossRefGoogle Scholar
  3. 3.
    Kawas CH, Brookmeyer R: Aging and the public health effects of dementia. N Engl J Med 2001, 344:1160–1161.PubMedCrossRefGoogle Scholar
  4. 4.
    Petersen RC, Doody R, Kurz A, et al.: Current concepts in mild cognitive impairment. Arch Neurol 2001, 58:1985–1992. Important study.PubMedCrossRefGoogle Scholar
  5. 5.
    Leibson C, Owens T, O’Brien P, et al.: Use of physician and acute care services by persons with and without Alzheimer’s disease: a population-based comparison. J Am Geriatr Soc 1999, 47:864–869.PubMedGoogle Scholar
  6. 6.
    Sano M, Albert SM, Tractenberg R, Schittini J: Developing utilities for stages of Alzheimer’s disease using the Clinical Dementia Rating. J Mental Health Aging 1999, 5:59–68.Google Scholar
  7. 7.
    Albert SM, Michaels K, Padilla M, et al.: Functional significance of mild cognitive impairment in elderly patients without a dementia diagnosis. Am J Geriatr Psychiatry 1999, 7:213–220.PubMedGoogle Scholar
  8. 8.
    Perenboom RJ, Boshuizen HC, Breteler MM, Ott A, Van de Water HP: Dementia-free life expectancy (DemFLE) in The Netherlands. Soc Sci Med 1996, 43:1703–1707.PubMedCrossRefGoogle Scholar
  9. 9.
    McKhann G, Drachman D, Folstein M, et al.: Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984, 34:939–945.PubMedGoogle Scholar
  10. 10.
    Small GW, Rabins PV, Barry PP, et al.: Diagnosis and treatment of Alzheimer’s disease and related disorders: consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer’s Association, and the American Geriatrics Society. J Am Med Assoc 1997, 278:1363–1371.CrossRefGoogle Scholar
  11. 11.
    Knopman DS, DeKosky ST, Cummings JL, et al.: Practice parameter: diagnosis of dementia (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001, 56:1143–1153.PubMedGoogle Scholar
  12. 12.
    Mudher A, Lovestone S: Alzheimer’s disease-do tauists and baptists finally shake hands? Trend Neurosci 2002, 25:22–26.PubMedCrossRefGoogle Scholar
  13. 13.
    Rabins PV: Developing treatment guidelines for Alzheimer’s disease and other dementias. J Clin Psychiatry 1998, 59(suppl)11:17–19.PubMedGoogle Scholar
  14. 14.
    Sano M, Ernesto C, Thomas RG, et al.: A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N Engl J Med 1997, 24:1216–1222.CrossRefGoogle Scholar
  15. 15.
    Le Bars PL, Katz MM, Berman N, et al.: A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA 1997, 278:1327–1332.PubMedCrossRefGoogle Scholar
  16. 16.
    Howard J, Taylor JA, Ganikos ML, et al.: An overview of prevention research: issues, answers, and agendas. Pub Health Rep 1988, 103:674–683.Google Scholar
  17. 17.
    Froom P, Benbassat J: Inconsistencies in the classification of preventive interventions. Prev Med 2000, 31:153–158.PubMedCrossRefGoogle Scholar
  18. 18.
    Yaffe K, Krueger K, Sarkar S, et al.: Multiple Outcomes of Raloxifene Evaluation Investigators. Cognitive function in postmenopausal women treated with raloxifene. N Engl J Med 2001, 344:1207–1213.PubMedCrossRefGoogle Scholar
  19. 19.
    Shepherd J, Blauw GJ, Murphy MB, et al.: The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk. Am J Cardiol 1999, 84:1192–1197.PubMedCrossRefGoogle Scholar
  20. 20.
    Grundman R: Use of brain MRI volumetric analysis in a mild cognitive impairment trial to delay the diagnosis of Alzheimer’s disease. In Drug Discovery and Development for Alzheimer’s Disease. Edited by Fillit H, O’Connell A. New York: Springer; 2002.Google Scholar
  21. 21.
    Tang MX, Jacobs D, Stern Y, et al.: Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet 1996, 348:429–432.PubMedCrossRefGoogle Scholar
  22. 22.
    Kawas C, Resnick S, Morrison A, et al.: A prospective study of estrogen replacement therapy and the risk of developing Alzheimer’s disease: The Baltimore Longitudinal Study of Aging. Neurology 1997, 48:1517–1521.PubMedGoogle Scholar
  23. 23.
    Yaffe K, Sawaya G, Lieberburg I, Grady D: Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. JAMA 1998, 279:688–695.PubMedCrossRefGoogle Scholar
  24. 24.
    LeBlanc ES, Janowsky J, Chan BK, Nelson HD: Hormone replacement therapy and cognition: systematic review and meta-analysis. JAMA 2001, 285:1489–1499.PubMedCrossRefGoogle Scholar
  25. 25.
    Jacobs DM, Tang MX, Stern Y, et al.: Cognitive function in nondemented older women who took estrogen after menopause. Neurology 1998, 50:368–373.PubMedGoogle Scholar
  26. 26.
    Carlson MC, Zandi PP, Plassman BL, et al.: Hormone replacement therapy and reduced cognitive decline in older women: The Cache County Study. Neurology 2001, 57:2210–2216. Important study.PubMedGoogle Scholar
  27. 27.
    Asthana S, Craft S, Baker LD, et al.: Cognitive and neuroendocrine response to transdermal estrogen in postmenopausal women with Alzheimer’s disease: results of a placebo-controlled, double-blind, pilot study. Psychoneuroendocrinology 1999, 24:657–677.PubMedCrossRefGoogle Scholar
  28. 28.
    Wang PN, Liao SQ, Liu RS, et al.: Effects of estrogen on cognition, mood, and cerebral blood flow in AD: a controlled study. Neurology 2000, 54:2061–2066.PubMedGoogle Scholar
  29. 29.
    Henderson VW, Paganini-Hill A, Miller BL, et al.: Estrogen for Alzheimer’s disease in women. Randomized, double-blind, placebo-controlled trial. Neruology 2000, 54:295.Google Scholar
  30. 30.
    Mulnard R, Cotman CW, Kawas C, et al.: Estrogen Replacement Therapy for treatment of mild to moderate Alzheimer’s disease: a 1-year randomized controlled trial. JAMA 2000, 283:1007–1015.PubMedCrossRefGoogle Scholar
  31. 31.
    Gould E, Woolly CS, Frankfurt M, McEwen BS: Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J Neurosci 1990, 10:286–291.Google Scholar
  32. 32.
    Toran-Allerand CD, Miranda RC, Bentham WD, et al.: Estrogen receptors colocalize with low affinity nerve growth factor receptors in cholinergic neurons of the basal forebrain. Proc Natl Acad Sci U S A 1992, 89:4668–4672.PubMedCrossRefGoogle Scholar
  33. 33.
    Xu H, Sweeney D, Wang R, et al.: Generation of Alzheimer Β-amyloid protein in the trans-Golgi network in the apparent absence of vesicle formation. Proc Natl Ac Sci U S A 1997, 94:3748–3752.CrossRefGoogle Scholar
  34. 34.
    Petanceska SS, Nagy V, Frail D, Gandy S: Ovariectomy and 17Β-estradiol modulate the levels of Alzheimer’s amyloid Β peptides in brain. Exp Gerontol 2000, 35:1317–1325.PubMedCrossRefGoogle Scholar
  35. 35.
    Shumaker SA, Reboussin BA, Espeland MA, et al.: The Women’s Health Initiative Memory Study (WHIMS): a trial of the effect of estrogen therapy in preventing and slowing the progression of dementia. Controlled Clin Trials 1998, 19:604–621.PubMedCrossRefGoogle Scholar
  36. 36.
    Brookmeyer R, Gray S, Kawas C: Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am J Public Health 1998, 88:1337–1342.PubMedCrossRefGoogle Scholar
  37. 37.
    Rich JB, Rasmusson DX, Folstein MF, et al.: Nonsteroidal antiinflammatory drugs in Alzheimer’s disease. Neurology 1995, 45:51–55.PubMedGoogle Scholar
  38. 38.
    Stewart WF, Kawas C, Corrada M, Metter EJ: Risk of Alzheimer’s disease and duration of NSAID use. Neurology1 1997, 48:626–632.Google Scholar
  39. 39.
    McGeer PL, McGeer E, Rogers J, Sibley J: Anti-inflammatory drugs and Alzheimer’s disease. Lancet 1990, 335:1037.PubMedCrossRefGoogle Scholar
  40. 40.
    Rogers J, Kirby LC, Hempelman SR, et al.: Clinical trial of indomethacin in Alzheimer’s disease. Neurology 1993, 43:1609–1611.PubMedGoogle Scholar
  41. 41.
    Scharf S, Mander A, Ugoni A, Vajda F, Christophidis N: A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer’s disease. Neurology 1999, 53:197–201.PubMedGoogle Scholar
  42. 42.
    Veld BA, Ruitenberg A, Hofman A, et al.: Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. N Engl J Med 2001, 345:1515–1521.CrossRefGoogle Scholar
  43. 43.
    Martin BK, Meinert CL, Breitner JC: Double placebo design in a prevention trial for Alzheimer’s disease. Controlled Clin Trials 2002, 23:93–99.PubMedCrossRefGoogle Scholar
  44. 44.
    Aisen PS, Davis KL: Inflammatory mechanism in Alzheimer’s disease: implications for therapy. Am J Psychiatry 1994, 151:1105–1113.PubMedGoogle Scholar
  45. 45.
    Aisen PS, Davis KL, Berg MD, et al.: A randomized controlled trial of prednisone in Alzheimer’s disease. Neurology 2000, 54:588–592.PubMedGoogle Scholar
  46. 46.
    Weggen S, Eriksen JL, Das P, et al.: A subset of NSAIDs lower amyloidogenic Ab42 independently of cyclooxygenase activity. Nature 2001, 414:212–216.PubMedCrossRefGoogle Scholar
  47. 47.
    Barkats M, Venault P, Christen Y, Cohen-Salmon C: Effect of long-term treatment with EGb 761 on age-dependent structural changes in the hippocampi of three inbred mouse strains. Life Sci 1995, 56:213–222.PubMedCrossRefGoogle Scholar
  48. 48.
    Scholtyssek H, Damerau W, Wessel R, Schimke I: Antioxidative activity of ginkgolides against superoxide in an aprotic environment. Chemico-Biol Interact 1997, 106:83–90.CrossRefGoogle Scholar
  49. 49.
    van Dongen MC, van Rossum E, Kessels AG, Sielhorst HJ, Knipschild PG: The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment: new results of a randomized clinical trial. J Am Geriatr Soc 2000, 48:1183–1194.PubMedGoogle Scholar
  50. 50.
    Ginkgo Biloba Prevention Trial in Older Individuals, RFA: AT-99-001, National Center for Complementary and Alternative Medicine and National Institute on Aging. February 26, 1999.Google Scholar
  51. 51.
    Clarke R, Smith AD, Jobst KA, et al.: Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998, 55:1449–1455.PubMedCrossRefGoogle Scholar
  52. 52.
    Joosten E, Lesaffre E, Riezler R, et al.: Is metabolic evidence for vitamin B-12 and folate deficiency more frequent in elderly patients with Alzheimer’s disease? J Gerontol A Biol Sci Med Sci 1997, 52:M76-M79.PubMedGoogle Scholar
  53. 53.
    Lehmann M, Gottfries CG, Regland B: Identification of cognitive impairment in the elderly: homocysteine is an early marker. Dement Geriatr Cogn Disord 1999, 10:12–20.PubMedCrossRefGoogle Scholar
  54. 54.
    McCaddon A, Davies G, Hudson P, Tandy S, Cattell H: Total serum homocysteine in senile dementia of Alzheimer type. Int J Geriatr Psychiatry 1998, 13:235–239.PubMedCrossRefGoogle Scholar
  55. 55.
    Nilson K, Gustafson L, Faldt R, et al.: Hyperhomocysteinaemia —a common finding in a psychogeriatric population. Eur J Clin Invest 1996, 26:853–859.CrossRefGoogle Scholar
  56. 56.
    Budge M, Johnston C, Hogervorst E, et al.: Plasma total homocysteine and cognitive performance in a volunteer elderly population. Ann NY Acad Sci 2000, 903:407–410.PubMedCrossRefGoogle Scholar
  57. 57.
    Frears ER, Stephens DJ, Walters CE, Davis H, Austen BM: The role of cholesterol in the biosynthesis of beta amyloid. Neuroreport 1999, 10:1699–1705.PubMedCrossRefGoogle Scholar
  58. 58.
    Sparks DL, Scheff SW, Hunsaker JC 3rd, et al.: Induction of Alzheimer-like beta-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol. Exp Neurol 1994, 126:88–94.PubMedCrossRefGoogle Scholar
  59. 59.
    Sparks DL, Liu H, Gross DR, Scheff SW: Increased density of cortical apolipoprotein E immunoreactive neurons in rabbit brain after dietary administration of cholesterol. Neurosci Lett 1995, 187:142–144.PubMedCrossRefGoogle Scholar
  60. 60.
    Streit WJ, Sparks DL: Activation of microglia in the brains of humans with heart disease and hypercholesterolemic rabbits. J Mol Med 1997, 5:130–138.CrossRefGoogle Scholar
  61. 61.
    Refolo LM, Pappolla MA, LaFrancois J, et al.: A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer’s disease. Neurobiol Dis 2001, 8:890–899.PubMedCrossRefGoogle Scholar
  62. 62.
    Desmond DW, Tatemichi TK, Paik M, Stern Y: Risk factors for cerebrovascular disease as correlates of cognitive function in a stroke-free cohort. Arch Neurol 1993, 50:162–166.PubMedGoogle Scholar
  63. 63.
    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, 57:1439–1443.PubMedCrossRefGoogle Scholar
  64. 64.
    Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA: Statins and the risk of dementia. Lancet 2000, 356:1627–1631.PubMedCrossRefGoogle Scholar
  65. 65.
    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.PubMedCrossRefGoogle Scholar
  66. 66.
    Collins R, Peto R, Armitage J: The MRC/BHF Heart Protection Study: preliminary results. Intl J Clin Pract 2002, 56:53–56. Important study.Google Scholar

Copyright information

© Current Science Inc 2002

Authors and Affiliations

  • Mary Sano
    • 1
  1. 1.Department of NeurologyCollege of Physicians and Surgeons of Columbia UniversityNew YorkUSA

Personalised recommendations