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Prevention of dementia

Daniel Press, MD
Michael Alexander, MD
Section Editors
Steven T DeKosky, MD, FAAN, FACP, FANA
Kenneth E Schmader, MD
Deputy Editor
April F Eichler, MD, MPH


Dementia is an increasing problem, primarily affecting elderly patients. Alzheimer disease (AD) is the most common form of dementia in the elderly, accounting for 60 to 80 percent of cases. Asymptomatic patients often present with concerns about developing dementia, especially when they have a family history.

An analysis based upon the observed prevalence of potentially modifiable risk factors (hypertension, diabetes, inactivity) combined with their associated relative risk for dementia suggests that risk factor reductions of 10 to 25 percent may prevent up to half of AD cases [1]. Although population-based data are not entirely consistent, it does appear that the incidence of all-cause dementia, and especially vascular dementia, is declining in high-income countries over the past several decades [2-6]. This trend has occurred as the prevalence of many vascular risk factors has also decreased over time [2]. While evidence is still lacking to support the routine use of any of these measures for the specific indication of preventing AD or dementia [7,8], epidemiologic studies offer optimism that multimodality risk factor reduction is worthwhile, not just for cardiovascular outcomes but also for cognitive health.

Related material concerning risk factors for dementia is discussed separately. The risk factors, treatment, and prevention of vascular dementia are discussed separately. (See "Risk factors for cognitive decline and dementia" and "Etiology, clinical manifestations, and diagnosis of vascular dementia" and "Treatment and prevention of vascular dementia".)

The recognition and evaluation of dementia is discussed separately. The major types of dementia and the treatment of dementia are also discussed separately. (See "Evaluation of cognitive impairment and dementia" and "Treatment of dementia" and "Etiology, clinical manifestations, and diagnosis of vascular dementia" and "Clinical features and diagnosis of Alzheimer disease" and "Clinical features and diagnosis of dementia with Lewy bodies".)


Antioxidant vitamins — Some studies suggest that oxidative stress may be important in the pathogenesis of Alzheimer disease (AD):


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  1. Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol 2011; 10:819.
  2. Satizabal CL, Beiser AS, Chouraki V, et al. Incidence of Dementia over Three Decades in the Framingham Heart Study. N Engl J Med 2016; 374:523.
  3. Schrijvers EM, Verhaaren BF, Koudstaal PJ, et al. Is dementia incidence declining?: Trends in dementia incidence since 1990 in the Rotterdam Study. Neurology 2012; 78:1456.
  4. Rocca WA, Petersen RC, Knopman DS, et al. Trends in the incidence and prevalence of Alzheimer's disease, dementia, and cognitive impairment in the United States. Alzheimers Dement 2011; 7:80.
  5. Matthews FE, Arthur A, Barnes LE, et al. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II. Lancet 2013; 382:1405.
  6. Qiu C, von Strauss E, Bäckman L, et al. Twenty-year changes in dementia occurrence suggest decreasing incidence in central Stockholm, Sweden. Neurology 2013; 80:1888.
  7. Daviglus ML, Bell CC, Berrettini W, et al. National Institutes of Health State-of-the-Science Conference statement: preventing alzheimer disease and cognitive decline. Ann Intern Med 2010; 153:176.
  8. Daviglus ML, Plassman BL, Pirzada A, et al. Risk factors and preventive interventions for Alzheimer disease: state of the science. Arch Neurol 2011; 68:1185.
  9. Behl C. Amyloid beta-protein toxicity and oxidative stress in Alzheimer's disease. Cell Tissue Res 1997; 290:471.
  10. Christen Y. Oxidative stress and Alzheimer disease. Am J Clin Nutr 2000; 71:621S.
  11. Grundman M. Vitamin E and Alzheimer disease: the basis for additional clinical trials. Am J Clin Nutr 2000; 71:630S.
  12. 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; 336:1216.
  13. Dysken MW, Sano M, Asthana S, et al. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA 2014; 311:33.
  14. Morris MC, Beckett LA, Scherr PA, et al. Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Dis Assoc Disord 1998; 12:121.
  15. Masaki KH, Losonczy KG, Izmirlian G, et al. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 2000; 54:1265.
  16. Commenges D, Scotet V, Renaud S, et al. Intake of flavonoids and risk of dementia. Eur J Epidemiol 2000; 16:357.
  17. Engelhart MJ, Geerlings MI, Ruitenberg A, et al. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 2002; 287:3223.
  18. Morris MC, Evans DA, Bienias JL, et al. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA 2002; 287:3230.
  19. Foley DJ, White LR. Dietary intake of antioxidants and risk of Alzheimer disease: food for thought. JAMA 2002; 287:3261.
  20. Luchsinger JA, Tang MX, Shea S, Mayeux R. Antioxidant vitamin intake and risk of Alzheimer disease. Arch Neurol 2003; 60:203.
  21. Zandi PP, Anthony JC, Khachaturian AS, et al. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol 2004; 61:82.
  22. Dunn JE, Weintraub S, Stoddard AM, Banks S. Serum alpha-tocopherol, concurrent and past vitamin E intake, and mild cognitive impairment. Neurology 2007; 68:670.
  23. Devore EE, Grodstein F, van Rooij FJ, et al. Dietary antioxidants and long-term risk of dementia. Arch Neurol 2010; 67:819.
  24. Yaffe K, Clemons TE, McBee WL, et al. Impact of antioxidants, zinc, and copper on cognition in the elderly: a randomized, controlled trial. Neurology 2004; 63:1705.
  25. Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 2005; 352:2379.
  26. Kang JH, Cook N, Manson J, et al. A randomized trial of vitamin E supplementation and cognitive function in women. Arch Intern Med 2006; 166:2462.
  27. Kang JH, Cook NR, Manson JE, et al. Vitamin E, vitamin C, beta carotene, and cognitive function among women with or at risk of cardiovascular disease: The Women's Antioxidant and Cardiovascular Study. Circulation 2009; 119:2772.
  28. Grodstein F, Kang JH, Glynn RJ, et al. A randomized trial of beta carotene supplementation and cognitive function in men: the Physicians' Health Study II. Arch Intern Med 2007; 167:2184.
  29. Yaffe K. Antioxidants and prevention of cognitive decline: does duration of use matter? Arch Intern Med 2007; 167:2167.
  30. Clarke R, Bennett D, Parish S, et al. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. Am J Clin Nutr 2014; 100:657.
  31. Balion C, Griffith LE, Strifler L, et al. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology 2012; 79:1397.
  32. Grima NA, Pase MP, Macpherson H, Pipingas A. The effects of multivitamins on cognitive performance: a systematic review and meta-analysis. J Alzheimers Dis 2012; 29:561.
  33. Grodstein F, O'Brien J, Kang JH, et al. Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Ann Intern Med 2013; 159:806.
  34. Morris MC, Evans DA, Bienias JL, et al. Dietary fat intake and 6-year cognitive change in an older biracial community population. Neurology 2004; 62:1573.
  35. Kalmijn S, van Boxtel MP, Ocké M, et al. Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology 2004; 62:275.
  36. Okereke OI, Rosner BA, Kim DH, et al. Dietary fat types and 4-year cognitive change in community-dwelling older women. Ann Neurol 2012; 72:124.
  37. Engelhart MJ, Geerlings MI, Ruitenberg A, et al. Diet and risk of dementia: Does fat matter?: The Rotterdam Study. Neurology 2002; 59:1915.
  38. Wu S, Ding Y, Wu F, et al. Omega-3 fatty acids intake and risks of dementia and Alzheimer's disease: a meta-analysis. Neurosci Biobehav Rev 2015; 48:1.
  39. Zhang Y, Chen J, Qiu J, et al. Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: a dose-response meta-analysis of 21 cohort studies. Am J Clin Nutr 2016; 103:330.
  40. Morris MC, Evans DA, Bienias JL, et al. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol 2003; 60:940.
  41. Huang TL, Zandi PP, Tucker KL, et al. Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4. Neurology 2005; 65:1409.
  42. Morris MC, Evans DA, Tangney CC, et al. Fish consumption and cognitive decline with age in a large community study. Arch Neurol 2005; 62:1849.
  43. Barberger-Gateau P, Raffaitin C, Letenneur L, et al. Dietary patterns and risk of dementia: the Three-City cohort study. Neurology 2007; 69:1921.
  44. Virtanen JK, Siscovick DS, Longstreth WT Jr, et al. Fish consumption and risk of subclinical brain abnormalities on MRI in older adults. Neurology 2008; 71:439.
  45. Devore EE, Grodstein F, van Rooij FJ, et al. Dietary intake of fish and omega-3 fatty acids in relation to long-term dementia risk. Am J Clin Nutr 2009; 90:170.
  46. Schaefer EJ, Bongard V, Beiser AS, et al. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol 2006; 63:1545.
  47. Samieri C, Maillard P, Crivello F, et al. Plasma long-chain omega-3 fatty acids and atrophy of the medial temporal lobe. Neurology 2012; 79:642.
  48. Gu Y, Schupf N, Cosentino SA, et al. Nutrient intake and plasma β-amyloid. Neurology 2012; 78:1832.
  49. Morris MC, Brockman J, Schneider JA, et al. Association of Seafood Consumption, Brain Mercury Level, and APOE ε4 Status With Brain Neuropathology in Older Adults. JAMA 2016; 315:489.
  50. van de Rest O, Wang Y, Barnes LL, et al. APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline. Neurology 2016; 86:2063.
  51. Sydenham E, Dangour AD, Lim WS. Omega 3 fatty acid for the prevention of cognitive decline and dementia. Cochrane Database Syst Rev 2012; :CD005379.
  52. Chew EY, Clemons TE, Agrón E, et al. Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial. JAMA 2015; 314:791.
  53. Quinn JF, Raman R, Thomas RG, et al. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA 2010; 304:1903.
  54. Dai Q, Borenstein AR, Wu Y, et al. Fruit and vegetable juices and Alzheimer's disease: the Kame Project. Am J Med 2006; 119:751.
  55. Morris MC, Evans DA, Tangney CC, et al. Associations of vegetable and fruit consumption with age-related cognitive change. Neurology 2006; 67:1370.
  56. Kang JH, Ascherio A, Grodstein F. Fruit and vegetable consumption and cognitive decline in aging women. Ann Neurol 2005; 57:713.
  57. Ortega RM, Requejo AM, Andrés P, et al. Dietary intake and cognitive function in a group of elderly people. Am J Clin Nutr 1997; 66:803.
  58. Lee L, Kang SA, Lee HO, et al. Relationships between dietary intake and cognitive function level in Korean elderly people. Public Health 2001; 115:133.
  59. Scarmeas N, Stern Y, Tang MX, et al. Mediterranean diet and risk for Alzheimer's disease. Ann Neurol 2006; 59:912.
  60. Stavitsky K, Brickman AM, Scarmeas N, et al. The progression of cognition, psychiatric symptoms, and functional abilities in dementia with Lewy bodies and Alzheimer disease. Arch Neurol 2006; 63:1450.
  61. Scarmeas N, Stern Y, Mayeux R, et al. Mediterranean diet and mild cognitive impairment. Arch Neurol 2009; 66:216.
  62. Scarmeas N, Luchsinger JA, Schupf N, et al. Physical activity, diet, and risk of Alzheimer disease. JAMA 2009; 302:627.
  63. Féart C, Samieri C, Rondeau V, et al. Adherence to a Mediterranean diet, cognitive decline, and risk of dementia. JAMA 2009; 302:638.
  64. Gu Y, Nieves JW, Stern Y, et al. Food combination and Alzheimer disease risk: a protective diet. Arch Neurol 2010; 67:699.
  65. Psaltopoulou T, Sergentanis TN, Panagiotakos DB, et al. Mediterranean diet, stroke, cognitive impairment, and depression: A meta-analysis. Ann Neurol 2013; 74:580.
  66. Morris MC, Tangney CC, Wang Y, et al. MIND diet associated with reduced incidence of Alzheimer's disease. Alzheimers Dement 2015; 11:1007.
  67. Estruch R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013; 368:1279.
  68. Widmer RJ, Flammer AJ, Lerman LO, Lerman A. The Mediterranean diet, its components, and cardiovascular disease. Am J Med 2015; 128:229.
  69. Valls-Pedret C, Sala-Vila A, Serra-Mir M, et al. Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial. JAMA Intern Med 2015; 175:1094.
  70. Scarmeas N, Luchsinger JA, Mayeux R, Stern Y. Mediterranean diet and Alzheimer disease mortality. Neurology 2007; 69:1084.
  71. Devore EE, Kang JH, Breteler MM, Grodstein F. Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann Neurol 2012; 72:135.
  72. Henderson VW, St John JA, Hodis HN, et al. Long-term soy isoflavone supplementation and cognition in women: a randomized, controlled trial. Neurology 2012; 78:1841.
  73. Young J, Angevaren M, Rusted J, Tabet N. Aerobic exercise to improve cognitive function in older people without known cognitive impairment. Cochrane Database Syst Rev 2015; :CD005381.
  74. Sink KM, Espeland MA, Castro CM, et al. Effect of a 24-Month Physical Activity Intervention vs Health Education on Cognitive Outcomes in Sedentary Older Adults: The LIFE Randomized Trial. JAMA 2015; 314:781.
  75. Verhaeghen P, Marcoen A, Goossens L. Improving memory performance in the aged through mnemonic training: a meta-analytic study. Psychol Aging 1992; 7:242.
  76. Stuss DT, Robertson IH, Craik FI, et al. Cognitive rehabilitation in the elderly: a randomized trial to evaluate a new protocol. J Int Neuropsychol Soc 2007; 13:120.
  77. Troyer, AK. Improving memory, knowledge, satisfaction, and functioning via an education and intervention program for older adults. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2001; 8:256.
  78. Willis SL, Tennstedt SL, Marsiske M, et al. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA 2006; 296:2805.
  79. Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet 2015; 385:2255.
  80. Unverzagt FW, Guey LT, Jones RN, et al. ACTIVE cognitive training and rates of incident dementia. J Int Neuropsychol Soc 2012; 18:669.
  81. Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke 2011; 42:2672.
  82. Levi Marpillat N, Macquin-Mavier I, Tropeano AI, et al. Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis. J Hypertens 2013; 31:1073.
  83. Forette F, Seux ML, Staessen JA, et al. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med 2002; 162:2046.
  84. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265:3255.
  85. Prince MJ, Bird AS, Blizard RA, Mann AH. Is the cognitive function of older patients affected by antihypertensive treatment? Results from 54 months of the Medical Research Council's trial of hypertension in older adults. BMJ 1996; 312:801.
  86. Tzourio C, Anderson C, Chapman N, et al. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med 2003; 163:1069.
  87. Saxby BK, Harrington F, Wesnes KA, et al. Candesartan and cognitive decline in older patients with hypertension: a substudy of the SCOPE trial. Neurology 2008; 70:1858.
  88. Peters R, Beckett N, Forette F, et al. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial. Lancet Neurol 2008; 7:683.
  89. Anderson C, Teo K, Gao P, et al. Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies. Lancet Neurol 2011; 10:43.
  90. McGuinness B, Todd S, Passmore P, Bullock R. Blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia. Cochrane Database Syst Rev 2009; :CD004034.
  91. Diener HC, Sacco RL, Yusuf S, et al. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study. Lancet Neurol 2008; 7:875.
  92. Forette F, Seux ML, Staessen JA, et al. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 1998; 352:1347.
  93. Lithell H, Hansson L, Skoog I, et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003; 21:875.
  94. Staessen JA, Thijs L, Richart T, et al. Placebo-controlled trials of blood pressure-lowering therapies for primary prevention of dementia. Hypertension 2011; 57:e6.
  95. Williamson JD, Launer LJ, Bryan RN, et al. Cognitive function and brain structure in persons with type 2 diabetes mellitus after intensive lowering of blood pressure and lipid levels: a randomized clinical trial. JAMA Intern Med 2014; 174:324.
  96. Haag MD, Hofman A, Koudstaal PJ, et al. Duration of antihypertensive drug use and risk of dementia: A prospective cohort study. Neurology 2009; 72:1727.
  97. Yasar S, Schuchman M, Peters J, et al. Relationship Between Antihypertensive Medications and Cognitive Impairment: Part I. Review of Human Studies and Clinical Trials. Curr Hypertens Rep 2016; 18:67.
  98. McGuinness B, Todd S, Passmore P, Bullock R. The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease. Cochrane Database Syst Rev 2006; :CD004034.
  99. 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.
  100. 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.
  101. Yaffe K, Sawaya G, Lieberburg I, Grady D. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. JAMA 1998; 279:688.
  102. LeBlanc ES, Janowsky J, Chan BK, Nelson HD. Hormone replacement therapy and cognition: systematic review and meta-analysis. JAMA 2001; 285:1489.
  103. Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA 2003; 289:2651.
  104. Shumaker SA, Legault C, Kuller L, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004; 291:2947.
  105. Espeland MA, Rapp SR, Shumaker SA, et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004; 291:2959.
  106. Schneider LS. Estrogen and dementia: insights from the Women's Health Initiative Memory Study. JAMA 2004; 291:3005.
  107. Grimley Evans J, Malouf R, Huppert F, van Niekerk JK. Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people. Cochrane Database Syst Rev 2006; :CD006221.
  108. Broe GA, Grayson DA, Creasey HM, et al. Anti-inflammatory drugs protect against Alzheimer disease at low doses. Arch Neurol 2000; 57:1586.
  109. Beard CM, Waring SC, O'Brien PC, et al. Nonsteroidal anti-inflammatory drug use and Alzheimer's disease: a case-control study in Rochester, Minnesota, 1980 through 1984. Mayo Clin Proc 1998; 73:951.
  110. in 't Veld BA, Launer LJ, Hoes AW, et al. NSAIDs and incident Alzheimer's disease. The Rotterdam Study. Neurobiol Aging 1998; 19:607.
  111. Stewart WF, Kawas C, Corrada M, Metter EJ. Risk of Alzheimer's disease and duration of NSAID use. Neurology 1997; 48:626.
  112. Zandi PP, Anthony JC, Hayden KM, et al. Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County Study. Neurology 2002; 59:880.
  113. de Craen AJ, Gussekloo J, Vrijsen B, Westendorp RG. Meta-analysis of nonsteroidal antiinflammatory drug use and risk of dementia. Am J Epidemiol 2005; 161:114.
  114. in t' 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.
  115. Etminan M, Gill S, Samii A. Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies. BMJ 2003; 327:128.
  116. Kang JH, Grodstein F. Regular use of nonsteroidal anti-inflammatory drugs and cognitive function in aging women. Neurology 2003; 60:1591.
  117. Hayden KM, Zandi PP, Khachaturian AS, et al. Does NSAID use modify cognitive trajectories in the elderly? The Cache County study. Neurology 2007; 69:275.
  118. Szekely CA, Breitner JC, Fitzpatrick AL, et al. NSAID use and dementia risk in the Cardiovascular Health Study: role of APOE and NSAID type. Neurology 2008; 70:17.
  119. Vlad SC, Miller DR, Kowall NW, Felson DT. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology 2008; 70:1672.
  120. Arvanitakis Z, Grodstein F, Bienias JL, et al. Relation of NSAIDs to incident AD, change in cognitive function, and AD pathology. Neurology 2008; 70:2219.
  121. Zhou Y, Su Y, Li B, et al. Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Abeta42 by inhibiting Rho. Science 2003; 302:1215.
  122. Weggen S, Eriksen JL, Das P, et al. A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature 2001; 414:212.
  123. Lleó A, Berezovska O, Herl L, et al. Nonsteroidal anti-inflammatory drugs lower Abeta42 and change presenilin 1 conformation. Nat Med 2004; 10:1065.
  124. Kukar T, Murphy MP, Eriksen JL, et al. Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Abeta42 production. Nat Med 2005; 11:545.
  125. Breitner JC, Haneuse SJ, Walker R, et al. Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort. Neurology 2009; 72:1899.
  126. Sonnen JA, Larson EB, Walker RL, et al. Nonsteroidal anti-inflammatory drugs are associated with increased neuritic plaques. Neurology 2010; 75:1203.
  127. Szekely CA, Green RC, Breitner JC, et al. No advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. Neurology 2008; 70:2291.
  128. ADAPT Research Group, Lyketsos CG, Breitner JC, et al. Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial. Neurology 2007; 68:1800.
  129. ADAPT Research Group, Martin BK, Szekely C, et al. Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib. Arch Neurol 2008; 65:896.
  130. Kang JH, Cook N, Manson J, et al. Low dose aspirin and cognitive function in the women's health study cognitive cohort. BMJ 2007; 334:987.
  131. Price JF, Stewart MC, Deary IJ, et al. Low dose aspirin and cognitive function in middle aged to elderly adults: randomised controlled trial. BMJ 2008; 337:a1198.
  132. Wolozin B, Kellman W, Ruosseau P, et al. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000; 57:1439.
  133. Jick H, Zornberg GL, Jick SS, et al. Statins and the risk of dementia. Lancet 2000; 356:1627.
  134. 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.
  135. 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.
  136. Li G, Shofer JB, Rhew IC, et al. Age-varying association between statin use and incident Alzheimer's disease. J Am Geriatr Soc 2010; 58:1311.
  137. Haley RW, Dietschy JM. Is there a connection between the concentration of cholesterol circulating in plasma and the rate of neuritic plaque formation in Alzheimer disease? Arch Neurol 2000; 57:1410.
  138. Vega GL, Weiner MF, Lipton AM, et al. Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease. Arch Neurol 2003; 60:510.
  139. Fassbender K, Simons M, Bergmann C, et al. Simvastatin strongly reduces levels of Alzheimer's disease beta -amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci U S A 2001; 98:5856.
  140. Simons M, Keller P, De Strooper B, et al. Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc Natl Acad Sci U S A 1998; 95:6460.
  141. Kojro E, Gimpl G, Lammich S, et al. Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha -secretase ADAM 10. Proc Natl Acad Sci U S A 2001; 98:5815.
  142. Pedrini S, Carter TL, Prendergast G, et al. Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK. PLoS Med 2005; 2:e18.
  143. Snowdon DA, Greiner LH, Mortimer JA, et al. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA 1997; 277:813.
  144. 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.
  145. 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.
  146. Dufouil C, Richard F, Fiévet N, et al. APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: the Three-City Study. Neurology 2005; 64:1531.
  147. Bernick C, Katz R, Smith NL, et al. Statins and cognitive function in the elderly: the Cardiovascular Health Study. Neurology 2005; 65:1388.
  148. 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.
  149. Li G, Larson EB, Sonnen JA, et al. Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease. Neurology 2007; 69:878.
  150. Szwast SJ, Hendrie HC, Lane KA, et al. Association of statin use with cognitive decline in elderly African Americans. Neurology 2007; 69:1873.
  151. Arvanitakis Z, Schneider JA, Wilson RS, et al. Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology 2008; 70:1795.
  152. 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.
  153. 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.
  154. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360:7.
  155. 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.
  156. McGuinness B, Craig D, Bullock R, Passmore P. Statins for the prevention of dementia. Cochrane Database Syst Rev 2016; :CD003160.
  157. Shepardson NE, Shankar GM, Selkoe DJ. Cholesterol level and statin use in Alzheimer disease: II. Review of human trials and recommendations. Arch Neurol 2011; 68:1385.
  158. DeKosky ST, Williamson JD, Fitzpatrick AL, et al. Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA 2008; 300:2253.
  159. Snitz BE, O'Meara ES, Carlson MC, et al. Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial. JAMA 2009; 302:2663.
  160. Vellas B, Coley N, Ousset PJ, et al. Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial. Lancet Neurol 2012; 11:851.