Biomedical papers, 2012 (vol. 156), no 2

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012, 156(2):108-114

Epidemiological of and risk factors for Alzheimer‘s disease: A review

Jana Povovaa, Petr Ambroza, Michal Barb, Veronika Pavukovaa, Omar Seryc, Hana Tomaskovaa, Vladimir Janouta
a Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Czech Republic
b Department of Clinical Studies, Faculty of Medicine, University of Ostrava
c Department of Biochemistry, Faculty of Science, Masaryk University Brno
DOI: 10.5507/bp.2012.055
Keywords: Alzheimer’s disease, epidemiology, risk factors, prevention

Received: September 9, 2011; Accepted: May 17, 2012; Available online: June 14, 2012


Background: Alzheimer's disease (AD) is the most common form of dementia. It is a degenerative, incurable and terminal disease. The increasing prevalence of AD is, among other reasons, due to population aging, which is, to a certain extent, seen worldwide. Continuous advances in health care keep increasing life expectancy. Official statistics are likely to significantly underestimate the actual prevalence of AD. Alzheimer's disease represents an important public health problem. Its aetiology is still unknown and for this reason, it is necessary to study all potential risk factors which may contribute to the development of this disease.

Methods: We searched original and review articles addressing Alzheimer's disease using key words Alzheimer's disease, epidemiology, risk factors and prevention. We found and used one hundred and four references.

Conclusions: Based on epidemiological studies, genetic studies, neuroimaging methods and neuropathology research, three basic etiological hypotheses of the development of AD have been formulated: genetic, vascular and psychosocial. At present, the level of evidence is insufficient for the etiological role of other factors, such as nutrition, occupational exposure to various substances and inflammation. From the point of view of early diagnosis and application of primary or secondary prevention principles, genetic factors are the most important.



Open full article

References

  1. Lobo A, Launer LJ, Fratiglioni L, Andersen K, Di Carlo A, Breteler MM,Copeland JR, Dartigues JF, Jagger C, Martinez-Lage J, Soininen H,Hofman A. Prevalence of demen tia and major subtypes in Europe:A collaborative study of population-based cohorts. Neurology 2000;54:S4-9 Go to pubmed...
  2. Plassman BL, Langa KM, Fischer GG, Hee ringa SG, DR Weir, Ofstedal MB, Burke JR, Hurd MD, Potter GG, Rodgers WL, Steffens DC, Willis RJ, Wallace RB. Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology 2007;29:125-32. Go to original source... Go to pubmed...
  3. Ferri CP, Prince M, Brayne C, Bro daty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M. Global prevalence of dementia: a Delphi consensus study. Lancet 2005;366:2112-7. Go to original source... Go to pubmed...
  4. von Strauss E, Viitanen M, De Ronchi D, Winblad B, Fratiglioni L. Aging and the occurrence of dementia: findings from a populationbased cohort with a large sample of nonagenarians. Arch Neurol 1999;56:587-92. Go to original source... Go to pubmed...
  5. Corrada MM, Brookmeyer R, Berlau D, Paganini-Hill A, Kawas CH. Prevalence of dementia after age 90: results from The 90+ Study. Neurology 2008;71:337-43. Go to original source... Go to pubmed...
  6. 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;54:2072-7. Go to original source... Go to pubmed...
  7. Kukull WA, Higdon R, Bowen JD, McCormick WC, Teri L, Schellenberg GD, van Belle G, Jolley L, Larson EB. Dem entia and Alzheimer disease incidence: a prospective cohort study. Arch Neurol 2002;59:1737-46. Go to original source... Go to pubmed...
  8. Fratiglioni L, Viitanen M, von Strauss E, Tontodonati V, Herlitz A, Winblad B. Very old women at highest risk of dementia and Alzheimer's disease: Incidence data from the Kungnsholmen Project, Stockholm. Neurology 1997;48,132-8. Go to original source... Go to pubmed...
  9. Copeland JRM, Davidson IA, Dewey ME Gilmore C, Larkin BA, McWilliam C, Saunders PA, Scott, Sharma V, Sullivan C. Alzheimer ´s disease other dementias, depression and pseudodementia: Prevalence, Incidence and Three Year Outcome in Liverpool. Br J Psychiatry 1992;161,230-9. Go to original source... Go to pubmed...
  10. Koukolik F., Jirak R. Alzheimerova nemoc a dalsi demence, Galen,1998.
  11. Fratiglioni L, von Strauss E, Qiu CX. Epidemiology of the dementias of old age. In Dening T, Jacoby R, Oppenheimer C, Thomas A, eds. The Oxford Textbook of Old Age Psychiatry. 4th ed. New York, NY: Oxford University Press 2008;391-406.
  12. Blennow K, de Leon MJ, Zetterberg H. Alzheimer's disease. Lancet 2006;368:387-403. Go to original source... Go to pubmed...
  13. Green RC, Cupples LA, Go R, Benke KS, Edeki T, Griffith PA, Williams M, Hipps Y, Gr aff-Radford N, Bachman D, Farrer LA.Risk of dementia among white and African American relatives of patients with Alzheimer disease. JAMA 2002;287:329-36. Go to original source... Go to pubmed...
  14. Huang W, Qiu C, von Strauss E, Winblad B, Fratiglioni L. APOE genotype, family history of dementia, and Alzheimer disease risk: a 6-year follow-up study. Arch Neurol 2004;61:1930-4. Go to original source... Go to pubmed...
  15. Qiu C, Kivipelto M, Agüero-Torres H, Winblad B, Fratiglioni L. Risk and protective effects of the APOE gene towards Alzheimer's disease in the Kungsholmen project: variation by age and sex. J Neurol Neurosurg Psychiatry 2004;75:828-33. Go to original source... Go to pubmed...
  16. Fratiglioni L, Wang HX. Smoking and Parkinson's and Alzheimer's disease: review of the epidemiological studies. Behav Brain Res 2000;113:117-20. Go to original source... Go to pubmed...
  17. Wang HX, Fratiglioni L, Frisoni GB, Viitanen M, Winblad B. Smoking and the occurrence of Alzheimer's disease: cross-sectional and longitudinal data in a population-based study. Am J Epidemiol 1999;149:640-4. Go to original source... Go to pubmed...
  18. Hill G, Connelly J, Hébert R, Lindsay J, Millar W. Neymans bias revisited. J Clin Epidemiol 2003;56:293-6. Go to original source... Go to pubmed...
  19. Tyas SL, White LR, Petrovitch H, Webster Ross G, Foley DJ, Heimovitz HK, Launer LJ. Mid-life smoking and late-life dementia: the Honolulu-Asia Aging Study. Neurobiol Aging 2003;24:589-96. Go to original source... Go to pubmed...
  20. Ott A, Slooter AJ, Hofman A, van Harskamp F, Witteman JC, Van Broeckhoven C, van Duijn CM, Breteler MM. Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study. Lancet 1998;351:1840-3. Go to original source... Go to pubmed...
  21. Merchant C, Tang MX, Albert S, Manly J, Stern Y, Mayeux R. The influence of smoking on the risk of Alzheimer's disease. Neurology 1999;52:1408-12. Go to original source... Go to pubmed...
  22. Aggarwal NT, Bienias JL, Ben nett DA, Wilson RS, Morris MC, Schneider JA, Shah RC, Evans DA. The relation of cigarette smoking to incident Alzheimer's disease in a biracial urban community population. Neuroepidemiology 2006;26:140-6. Go to original source... Go to pubmed...
  23. Anstey KJ, von Sanden C, Salim A, O'Kearney R. Smoking as a risk factor for dementia and cognitive decline: a meta-analysis of prospective studies. Am J Epidemiol 2007;166:367-78. Go to original source... Go to pubmed...
  24. Peters R, Poulter R, Warner J, Beckett N, Burch L, Bulpitt C. Smoking, dementia and cognitive decline in the elderly, a systematic review. BMC Geriatr 2008;8:36. Go to original source... Go to pubmed...
  25. Anttila T, Helkala EL, Viitanen M, Kareholt I, Fratiglioni L, Winblad B, Soininen H, Tuomilehto J, Nissinen A, Kivipelto M. Alcohol drinking in middle age and subsequent risk of mild cognitive impairment and dementia in old age: a prospective population based study. BMJ 2004;329:539. Go to original source... Go to pubmed...
  26. Huang W, Qiu C, Winblad B, Fratiglioni L. Alcohol consumption and incidence of dementia in a community sample aged 75 years and older. J Clin Epidemiol 2002;55:959-64. Go to original source... Go to pubmed...
  27. Ruitenberg A, van Swieten JC, Witteman JC, Mehta KM, van Duijn CM, Hofman A, Breteler MM. Alcohol consumption and risk of dementia: the Rotterdam Study. Lancet 2002;359:281-6. Go to original source... Go to pubmed...
  28. Ding J, Eigenbrodt ML, Mosley TH Jr, Hutchinson RG, Folsom AR, Harris TB, Nieto FJ. Alcohol intake and cerebral abnormalities on magnetic resonance imaging in a c ommunity-based population of middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) study. Stroke 2004;35:16-21. Go to original source... Go to pubmed...
  29. Paul CA, Au R, Fredman L, Massaro JM, Seshadri S, Decarli C, Wolf PA. Association of alcohol consumption with brain volume in the Framingham study. Arch Neurol 2008;65:1363-7. Go to original source... Go to pubmed...
  30. Kivipelto M, Ngandu T, Fratiglioni L, M Viitanen, Kareholt I, Winblad B, Helkala EL, Tuomilehto J, H Soininen, Nissinen A. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol 2005;62:1556-60. Go to original source... Go to pubmed...
  31. Rosengren A, Skoog I, Gustafson D, Wilhelmsen L. Body mass index, other cardiovascular risk factors, and hospitalization for dementia. Arch Intern Med 2005;165:321-6. Go to original source... Go to pubmed...
  32. Whitmer RA, Gunderson EP, Barrett-Connor E, Quesenberry CP Jr., Yaffe K. Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study. BMJ 2005;330:1360. Go to original source... Go to pubmed...
  33. Fitzpatrick AL, Kul ler LH, Lopez OL, Diehr P, O'Meara ES, Longstreth WT Jr, Luchsinger JA. Midlife and late-life obesity and the risk of dementia : cardiovascular health study. Arch Neurol 2009;66:336-42. Go to original source... Go to pubmed...
  34. Buchman AS, Wilson RS, Bienias JL, Shah RC, Evans DA, Bennett DA. Change in body mass index and risk of incident Alzheimer disease. Neurology 2005;65:892-7. Go to original source... Go to pubmed...
  35. Johnson DK, Wilkins CH, Morris JC. Accelerated weight loss may precede diagnosis in Alzheimer disease. Arch Neurol 2006;63:1312-7. Go to original source... Go to pubmed...
  36. Dahl AK, Löppönen M, Isoaho R, Berg S, Kivelä SL. Overweight and obesity in old age are not associated with greater dementia risk. J Am Geriatr Soc 2008;56:2261-66. Go to original source... Go to pubmed...
  37. Nourhashemi F, Deschamps V, Larrieu S, Letenneur L, Dartigues JF, Barberger-Gateau P. Body mass index and incidence of dementia: the PAQUID study. Neurology 2003;60:117-9. Go to original source... Go to pubmed...
  38. Atti AR, Palmer K, Volpato S, Winblad B, De Ronchi D, Fratiglioni L. Late-life body mass index and dementia incidence: nine-year follow-up data from the Kungsholmen Project. J Am Geriatr Soc 2008;56:111-6. Go to original source... Go to pubmed...
  39. Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, Havlik RJ. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging 2000;21:49-55. Go to original source... Go to pubmed...
  40. Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ 2001;322:1447-51. Go to original source... Go to pubmed...
  41. Qiu C, Winblad B, Fratiglioni L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol 2005;4:487-99. Go to original source... Go to pubmed...
  42. Skoog I, Lernfelt B, Landahl S, Palmertz B, Andreasson LA, Nilsson L, Persson G, Oden A, Svanborg A. 15-year longitudinal study of blood pressure and dementia. Lancet 1996;347:1141-5. Go to original source... Go to pubmed...
  43. Petitti DB, Crooks VC, Buckwalter JG, Chiu V. Blood pressure levels before dementia. Arch Neurol 2005;62:112-6. Go to original source... Go to pubmed...
  44. Morris MC, Scherr PA, Hebert LE, Glynn RJ, Benne tt DA, Evans DA. Association of incident Alzheimer disease and blood pressure measured from 13 years before to 2 years after diagnosis in a large community study. Arch Neurol 2001;58:1640-6. Go to original source... Go to pubmed...
  45. Qiu C, von Strauss E, Fastbom J, Winblad B, Fratiglioni L. Low blood pressure and risk of dementia in the Kungsholmen project: a 6-year follow-up study. Arch Neurol 2003;60:223-8. Go to original source... Go to pubmed...
  46. Verghese J, Lipton RB, Hall CB, Kuslansky G, Katz MJ. Low blood pressure and the risk of dementia in very old individuals. Neurology 2003;61:1667-72. Go to original source... Go to pubmed...
  47. Ruitenberg A, den Heijer T, Bakker SL, van Swieten JC, Koudstaal PJ, Hofman A, Breteler MM. Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol 2005;57:789-94. Go to original source... Go to pubmed...
  48. Yasar S, Corrada M, Broo kmeyer R, Kawas C. Calcium channel blockers and risk of AD: the Baltimore Longitudinal Study of Aging. Neurobiol Aging 2005;26:157-63. Go to original source... Go to pubmed...
  49. Khachaturian AS, Zandi PP, Lyketsos CG, Hayden KM, Skoog I, Norton MC, Tschanz JT, Mayer LS, Welsh-Bohmer KA, Breitner JC. Antihypertensive medication use and incident Alzheimer disease: the Cache County Study. Arch Neurol 2006;63:686-92. Go to original source... Go to pubmed...
  50. Peila R, White LR, Masaki K, Petrovitch H, Launer LJ. Reducing the risk of dementia: efficacy of long-term treatment of hypertension. Stroke 2006;37:1165-70. Go to original source... Go to pubmed...
  51. Haag MD, Hofman A, Koudstaal PJ, Breteler MM, Stricker BH. Duration of antihypertensive drug use and risk of dementia. A prospective cohort study. Neurology 2009;72:1727-34. Go to original source... Go to pubmed...
  52. Kivipelto M, Helkala EL, Laakso MP, Hänninen T, M Hallikainen, Alhainen K, Iivonen S, Mannermaa, Tuomilehto J, Nissinen, Soininen H. Apolipoprotein E Â4 allele, elevated midlife total cholesterol l evel, and high midlife systolic blood pressure are independent risk factors for late-lif e Alzheimer disease. Ann Intern Med 2002;137:149-55. Go to original source... Go to pubmed...
  53. Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K. Midlife cardiovascular risk factors and risk of dementia in late life. Neurology 2005;64:277-81. Go to original source... Go to pubmed...
  54. Solomon A, Kareholt I, Ngandu T, Winblad B, Nissinen, Tuomilehto J, H Soininen, Kivipelto M. Serum chol esterol changes after midlife and late-life cognition: twenty-one-year follow-up study. Neurology 2007;68:751-6. Go to original source... Go to pubmed...
  55. Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet 2000;356:1627-31. Go to original source... Go to pubmed...
  56. Rockwood K, Kirkland S, Hogan DB, MacKnight C, Merry H, Verreault R, Wolfson C, McDowell I. Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch Neurol 2002;59:223-7. Go to original source... Go to pubmed...
  57. Haag MD, Hofman A, Koudstaal PJ, Stricker BH, Breteler MM. Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity: the Rotterdam Study. J Neurol Neurosurg Psychiatry 2009;80:13-7. Go to original source... Go to pubmed...
  58. Rea TD, Breitner JC, Psaty BM, Fitzpatrick AL, Lopez OL, Newman AB, Hazzard WR, Zandi PP, Burke GL, Lyketsos CG, Bernick C, Kuller LH. Statin use and the risk of incident dementia: the Cardiovascular Health Study. Arch Neurol 2005;62:1047-51. Go to original source... Go to pubmed...
  59. Zandi PP, Sparks DL, Khachaturian AS, Khachaturian AS, Tschanz J, Norton M, Steinberg M, Welsh-Bohmer KA, Breitner JC. Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch Gen Psychiatry 2005;62:217-24. Go to original source... Go to pubmed...
  60. Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JC. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol 2004;61:82-8. Go to original source... Go to pubmed...
  61. Barberger-Gateau P, Raffaitin C, Letenneur L, C Berr, Tzourio C, Dartigues JF, Alpérovitch A. et al. Dietary patterns and risk of dementia: the Three-City cohort study. Neurology 2007;69:1921-30. Go to original source... Go to pubmed...
  62. Gray SL, Anderson ML, Crane PK, Breitner JC, McCormick W, Bowen JD, Teri L, Larson E. Antioxidant vitamin supplement use and risk of dementia or Alzheimer's disease in older adults. J Am Geriatr Soc 2008;56:291-5. Go to original source... Go to pubmed...
  63. Scarmeas N, Stern Y, Mayeux R, Luchsinger JA. Mediterranean diet, Alzheimer disease, and vascular mediation. Arch Neurol 2006;63:1709-17. Go to original source... Go to pubmed...
  64. Scarmeas N, Stern Y, Tang MX, Mayeux R, Luchsinger JA. Mediterranean diet and risk for Alzheimer's disease. Ann Neurol 2006;59:912-21. Go to original source... Go to pubmed...
  65. Malouf M, Grimley EJ, Areosa SA. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev 2003: CD004514.
  66. Laitinen MH, Ngandu T, Rovio S, Helkala EL, Uusitalo U, Viitanen M, Nissinen A, Tuomilehto J, Soininen H, Kivipelto M. Fat intake at midlife and risk of dementia and Alzheimer's disease: a populationbased study. Dement Geriatr Cog n Disord 2006;22:99-107. Go to original source... Go to pubmed...
  67. Huang TL, Zandi PP, Tucker KL, Fitzpatrick AL, Kuller LH, Fried LP, Burke GL, Carlson MC. Benefits of fatty fish on dementia risk are stronger for those without APOE e4. Neurology 2005;65:1409-14. Go to original source... Go to pubmed...
  68. Schaefer EJ, Bongard V, Beiser AS, Lamon-Fava S, Robins SJ, Au R, Tucker KL, Kyle DJ, Wilson PW, Wolf PA. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol 2006;63:1545-50. Go to original source... Go to pubmed...
  69. Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol 2004;61:661-6. Go to original source... Go to pubmed...
  70. Akomolafe A, Beiser A, Meigs JB, Au R, Green RC, Farrer LA, Wolf PA, Seshadri S. Diabetes mellitus and risk of developing Alzheimer disease: results from the Framingham Study. Arch Neurol 2006;63:1551-5. Go to original source... Go to pubmed...
  71. Irie F, Fitzpatrick AL, Lopez OL, et al. Enhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE e4: the Cardiovascular Health Study Cognition Study. Arch Neurol 2008;65:89-93. Go to original source... Go to pubmed...
  72. Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of Dementia in diabetes mellitus: a systematic review. Lancet Neurol 2006;5:64-74. Go to original source... Go to pubmed...
  73. Roberts RO, Geda YE, Knopman DS, Christianson TJ, Pankratz VS, Boeve BF, Vella A, Rocca WA, Petersen RC. Association of duration and severity of diabetes mellitus with mild cognitive impairment. Arch Neurol 2008;65:1066-73. Go to original source... Go to pubmed...
  74. Xu W, Qiu C, Gatz M, Pedersen NL, Johansson B, Fratiglioni L. Midand late-life diabetes in relation to the risk of dementia: a population-based twin study. Diabetes 2009;58:71-7. Go to original source... Go to pubmed...
  75. Xu WL, Qiu CX, Winblad B, Fratiglioni L. The effect of borderline dia- betes mellitus on the risk of dementia and Alzheimer disease. Diabetes 2007;56:211-6. Go to original source... Go to pubmed...
  76. Korf ES, White LR, Scheltens P, Launer LJ. Brain aging in very old men with type 2 diabetes: the Honolulu-Asia Aging Study. Diabetes Care 2006;29:2268-74. Go to original source... Go to pubmed...
  77. Rönnemaa E, Zethelius B, Sundelöf J, Sundström J, Degerman-Gunnarsson M, Berne C, Lannfelt L, Kilander L. Impaired insulin secretio n increases the risk of Alzheimer disease. Neurology 2008;71:1065-71. Go to original source... Go to pubmed...
  78. Xu WL, von Strauss E, Qiu CX, Winblad B, Fratiglioni L. Uncontrolled diabetes increases the risk of Alz heimer's disease: a populationbased cohort study. Diabetologia 2009;52:1031-9. Go to original source... Go to pubmed...
  79. Vanhanen M, Koivisto K, Moilanen L, Helkala EL, Hänninen T, Soininen H, K Kervinen, Kesäniemi YA, Laakso M, Kuusisto J. Association of metabolic syndrome with Alzheimer disease: a population-based study. Neurology 2006;67:843-7. Go to original source... Go to pubmed...
  80. Muller M, Tang MX, Schupf N, Manly JJ, Mayeux R, Luchsinger JA. Metabolic syndrome and dementia risk in a multiethnic elderly cohort. Dement Geriatr Cogn Disord 2007;24:185-92. Go to original source... Go to pubmed...
  81. Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003;348:1215-22. Go to original source... Go to pubmed...
  82. Honig LS, Tang MX, Albert S, R Costa, Luchsinger J, J Manly, Stern Y, Mayeux R. Stroke and the risk of Alzheimer disease. Arch Neurol 2003;60:1707-12. Go to original source... Go to pubmed...
  83. Newman AB, Fitzpatrick AL, Lopez O, Jackson S, Lyketsos C, Jagust W, Ives D, Dekosky ST, Kuller LH. Dementia and Alzheimer's disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort. J Am Geriatr Soc 2005;53:1101-7. Go to original source... Go to pubmed...
  84. Beeri MS, Rapp M, Silverman JM, Schmeidler J, Grossman HT, Fallon JT, Purohit DP, Perl DP, Siddiqui A, Lesser G, Rosendorff C, Haroutunian V. Coronary artery disease is associated with Alzheimer disease neuropathology in APOE4 carriers. Neurology 2006;66:1399-1404. Go to original source... Go to pubmed...
  85. Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer disease: the Nun Study. JAMA 1997;277:813-7. Go to original source... Go to pubmed...
  86. Esiri MM, Nagy Z, Smith MZ, Barnetson L, Smith AD. Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer's disease. Lancet 1999;354:919-20. Go to original source... Go to pubmed...
  87. Fratiglioni L, Paillard-Borg S, Winblad B. An active and socially integrated lifestyle in late life might protect against dementia. Lancet Neurol 2004;3:343-53. Go to original source... Go to pubmed...
  88. Qiu C, Bäckman L, Winblad B, Agüero-Torres H, Fratiglioni L. The influence of education on clinically diagnosed dementia: incidence and mortality data from the Kungsholmen Project. Arch Neurol 2001;58:2034-9. Go to original source... Go to pubmed...
  89. Ngandu T, von Strauss E, Helkala EL, Winblad B, Nissinen A, Tuomilehto J, Soininen H, Kivipelto M. Education and dementia: what lies behind the association? Neurology 2007;69:1442-50. Go to original source... Go to pubmed...
  90. Karp A, Kareholt I, Qiu C, Bellander T, Winblad B, Fratiglion i L. Relation of education and occupation-based socioeconomic status to incident Alzheimer's disease. Am J Epidemiol 2004;159:175-83. Go to original source... Go to pubmed...
  91. Fratiglioni L, Wang HX, Ericsson K, Maytan M, Winblad B. Influence of social network on occurrence of dementia: a community-based longitudinal study. Lancet 2000;355:1315-9. Go to original source... Go to pubmed...
  92. Wang HX, Karp A, Herlitz A, Crowe M, Kareholt I, Winblad B, Fratiglioni L. Personality and lifestyle in relation to dementia incidence. Neurology 2009;72:253-9. Go to original source... Go to pubmed...
  93. Wang HX, K arp A, Winblad B, Fratiglioni L. Late-life engagement in social and leisure activities is associated with a decreased risk of dementia: a longitudinal study from the Kungsholmen project. Am J Epidemiol 2002;155:1081-7. Go to original source... Go to pubmed...
  94. Saczynski JS, Pfeifer LA, Masaki K, Korf ES, Laurin D, White L, Launer LJ. The effect of social engage- ment on incident dementia: the Honolulu-Asia Aging Study. Am J Epidemiol 2006;163:433-40. Go to original source... Go to pubmed...
  95. Larson EB, Wang L, Bowen JD, McCormick WC, Teri L, Crane P, Kukull W. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med 2006;144:73-81. Go to original source... Go to pubmed...
  96. Karp A, Paillard-Borg S, Wang HX, Silverstein M, Winblad B, Fratiglioni L. Mental, physical and social components in leisure activities equally contribute to decrease dementia risk. Dement Geriatr Cogn Disord 2006;21:65-73. Go to original source... Go to pubmed...
  97. Abbott RD, White LR, Ross GW, Masaki KH, Curb JD, Petrovitch H. Walking and dementia in physically capable elderly men. JAMA 2004;292:14 47-53. Go to original source... Go to pubmed...
  98. Rovio S, Kareholt I, Helkala EL, Viitanen M, Winblad B, Tuomilehto J, Soininen H, Nissinen A, Kivipelto M. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease. Lancet Neurol 2005;4:705-11. Go to original source... Go to pubmed...
  99. Crowe M, Andel R, Pedersen NL, Johansson B, Gatz M. Does participation in leisure activities lead to reduced risk of Alzheimer's disease? A prospective study of Swedish twins. J Gerontol B Psychol Sci Soc Sci 2003;58:249-55. Go to original source...
  100. Andel R, Crowe M, Pedersen NL, Mortimer J, Crimmins E, Johansson B, Gatz M. Complexity of work and risk of Alzheimer's disease: a population-based study of Swedish twins. J Gerontol B Psychol Sci Soc Sci 2005;60:251-8. Go to original source...
  101. Valenzuela MJ, Sachdev P, Wen W, Chen X, Brodaty H. Lifespan mental activity predicts diminished rate of hippocampal atrophy. PLoS ONE 2008;3:e2598. Go to original source... Go to pubmed...
  102. Qiu CX, De Ronchi D, Fratiglioni L. The epidemiology of the dementias: an update. Curr Opin Psychiatry 2007;20:380-5. Go to original source... Go to pubmed...
  103. Bäckm an L, Small BJ, Fratiglioni L. Stability of the preclinical episodic memory deficit in Alzheimer's disease. Brain 2001;124:96-102. Go to original source... Go to pubmed...
  104. DeKosky ST, Marek K. Looking backward to move forward: early detectio n of neurodegenerative disorders. Science 2003;302:830-4. Go to original source... Go to pubmed...