J Korean Med Sci.  2014 Jul;29(7):886-892. 10.3346/jkms.2014.29.7.886.

Primary Prevention of Alzheimer's Disease: Is It an Attainable Goal?

Affiliations
  • 1Department of Neurology, Seoul National University Hospital, Seoul, Korea.
  • 2Department of Neurology, Konkuk University School of Medicine, Seoul, Korea. alzdoc@kuh.ac.kr
  • 3Center for Geriatric Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Korea.

Abstract

Alzheimer's disease (AD) is the leading cause of dementia, and the most prevalent neurodegenerative disease in the elderly. The prevalence of AD is predicted to rise as life expectancy grows across populations. The exact cause of this devastating disease is still unknown; however, it is an aging-related multi-factorial disorder, and growing evidence supports the contribution of modifiable environmental factors to unmodifiable factors such as gene and ageing itself. The recent advancement of methodologies and techniques for early diagnosis of AD facilitates the investigation of strategies to reduce the risk for AD progression in the earliest stages of the disease. Pharmacological attempts at curing, halting or modifying it have, by and large, been unsuccessful, and no breakthrough is seen in the near future. However, a lot of elements that seem to contribute to the disease such as risk factors have been identified, mainly from epidemiological and basic research studies. Many of these are amenable to lifestyle modification. Therefore, prevention in the preclinical stage is likely the most effective way to decrease the incidence of this age-associated dreadful neurodegenerative condition, and its associated burden for individuals and society. We provide an overview of modifiable risk factors for AD along with the supporting evidence.

Keyword

Alzheimer's Disease; Primary Prevention; Lifestyle Modification; Nutrition

MeSH Terms

Alzheimer Disease/epidemiology/*prevention & control
Cognitive Therapy
Dietary Supplements
Health Behavior
Humans
Mind-Body Therapies
Motor Activity
Risk Factors

Reference

1. United Nations, Department of Economic and Social Affairs, Population Division. World population prospects: the 2012 revision, key findings and advance tables. 2013. No. ESA/P/WP.227.
2. Reitz C, Mayeux R. Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem Pharmacol. 2014; 88:640–651.
3. Ritchie CW, Zhinchin G. Low dose, high dose, or no dose: better prescribing of cholinesterase inhibitors for Alzheimer's disease. Int Psychogeriatr. 2013; 25:511–515.
4. Rosenblum WI. Why Alzheimer trials fail: removing soluble oligomeric beta amyloid is essential, inconsistent, and difficult. Neurobiol Aging. 2014; 35:969–974.
5. Smith AD, Yaffe K. Dementia (including Alzheimer's disease) can be prevented: statement supported by international experts. J Alzheimers Dis. 2014; 38:699–703.
6. Evans DA, Funkenstein HH, Albert MS, Scherr PA, Cook NR, Chown MJ, Hebert LE, Hennekens CH, Taylor JO. Prevalence of Alzheimer's disease in a community population of older persons: higher than previously reported. JAMA. 1989; 262:2551–2556.
7. Salthouse TA. Selective review of cognitive aging. J Int Neuropsychol Soc. 2010; 16:754–760.
8. Viswanathan A, Rocca WA, Tzourio C. Vascular risk factors and dementia: how to move forward? Neurology. 2009; 72:368–374.
9. Reitz C, Brayne C, Mayeux R. Epidemiology of Alzheimer disease. Nat Rev Neurol. 2011; 7:137–152.
10. Daviglus ML, Bell CC, Berrettini W, Bowen PE, Connolly ES Jr, Cox NJ, Dunbar-Jacob JM, Granieri EC, Hunt G, McGarry K, et al. NIH state-of-the-science conference statement: preventing Alzheimer's disease and cognitive decline. NIH Consens State Sci Statements. 2010; 27:1–30.
11. 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.
12. Luchsinger JA, Noble JM, Scarmeas N. Diet and Alzheimer's disease. Curr Neurol Neurosci Rep. 2007; 7:366–372.
13. Kivipelto M, Helkala EL, Laakso MP, Hänninen T, Hallikainen M, Alhainen K, Iivonen S, Mannermaa A, Tuomilehto J, Nissinen A, et al. Apolipoprotein E epsilon4 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.
14. 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.
15. Luchsinger JA, Tang MX, Stern Y, Shea S, Mayeux R. Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol. 2001; 154:635–641.
16. Reitz C, Brickman AM, Luchsinger JA, Wu WE, Small SA, Tang MX. Frequency of subclinical heart disease in elderly persons with dementia. Am J Geriatr Cardiol. 2007; 16:183–188.
17. Yaffe K, Weston AL, Blackwell T, Krueger KA. The metabolic syndrome and development of cognitive impairment among older women. Arch Neurol. 2009; 66:324–328.
18. Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013; 368:1279–1290.
19. Bekris LM, Yu CE, Bird TD, Tsuang DW. Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol. 2010; 23:213–227.
20. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer's disease. Alzheimers Dement. 2007; 3:186–191.
21. Valenzuela MJ, Sachdev P. Brain reserve and dementia: a systematic review. Psychol Med. 2006; 36:441–454.
22. Stern Y. What is cognitive reserve? theory and research application of the reserve concept. J Int Neuropsychol Soc. 2002; 8:448–460.
23. Alves J, Magalhães R, Thomas RE, Gonçalves OF, Petrosyan A, Sampaio A. Is there evidence for cognitive intervention in Alzheimer disease? a systematic review of efficacy, feasibility, and cost-effectiveness. Alzheimer Dis Assoc Disord. 2013; 27:195–203.
24. Rebok GW, Ball K, Guey LT, Jones RN, Kim HY, King JW, Marsiske M, Morris JN, Tennstedt SL, Unverzagt FW, et al. Ten-year effects of the advanced cognitive training for independent and vital elderly cognitive training trial on cognition and everyday functioning in older adults. J Am Geriatr Soc. 2014; 62:16–24.
25. Sofi F, Valecchi D, Bacci D, Abbate R, Gensini GF, Casini A, Macchi C. Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. J Intern Med. 2011; 269:107–117.
26. Lautenschlager NT, Cox KL, Flicker L, Foster JK, van Bockxmeer FM, Xiao J, Greenop KR, Almeida OP. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA. 2008; 300:1027–1037.
27. Pizzie R, Hindman H, Roe CM, Head D, Grant E, Morris JC, Hassenstab JJ. Physical activity and cognitive trajectories in cognitively normal adults: the adult children study. Alzheimer Dis Assoc Disord. 2014; 28:50–57.
28. Gomez-Pinilla F, Zhuang Y, Feng J, Ying Z, Fan G. Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation. Eur J Neurosci. 2011; 33:383–390.
29. Molteni R, Ying Z, Gómez-Pinilla F. Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarray. Eur J Neurosci. 2002; 16:1107–1116.
30. Ahlskog JE, Geda YE, Graff-Radford NR, Petersen RC. Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clin Proc. 2011; 86:876–884.
31. Eadie BD, Redila VA, Christie BR. Voluntary exercise alters the cytoarchitecture of the adult dentate gyrus by increasing cellular proliferation, dendritic complexity, and spine density. J Comp Neurol. 2005; 486:39–47.
32. Erickson KI, Prakash RS, Voss MW, Chaddock L, Hu L, Morris KS, White SM, Wójcicki TR, McAuley E, Kramer AF. Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus. 2009; 19:1030–1039.
33. Rovio S, Kåreholt 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; 4:705–711.
34. De la Torre JC. Is Alzheimer's disease a neurodegenerative or a vascular disorder? data, dogma, and dialectics. Lancet Neurol. 2004; 3:184–190.
35. Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American heart association/american stroke association. Stroke. 2011; 42:2672–2713.
36. Nishtala A, Preis SR, Beiser A, Devine S, Hankee L, Seshadri S, Wolf PA, Au R. Midlife cardiovascular risk impacts executive function: Framingham Offspring Study. Alzheimer Dis Assoc Disord. 2014; 28:16–22.
37. Qiu C, Winblad B, Fratiglioni L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol. 2005; 4:487–499.
38. Alonso A, Mosley TH Jr, Gottesman RF, Catellier D, Sharrett AR, Coresh J. Risk of dementia hospitalisation associated with cardiovascular risk factors in midlife and older age: the Atherosclerosis Risk in Communities (ARIC) Study. J Neurol Neurosurg Psychiatry. 2009; 80:1194–1201.
39. Qiu C, Winblad B, Fratiglioni L. Low diastolic pressure and risk of dementia in very old people: a longitudinal study. Dement Geriatr Cogn Disord. 2009; 28:213–219.
40. 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.
41. Craft S. The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged. Arch Neurol. 2009; 66:300–305.
42. Cukierman-Yaffe T, Gerstein HC, Williamson JD, Lazar RM, Lovato L, Miller ME, Coker LH, Murray A, Sullivan MD, Marcovina SM, et al. Relationship between baseline glycemic control and cognitive function in individuals with type 2 diabetes and other cardiovascular risk factors: the action to control cardiovascular risk in diabetes-memory in diabetes (ACCORD-MIND) trial. Diabetes Care. 2009; 32:221–226.
43. Wood WG, Li L, Muller WE, Eckert GP. Cholesterol as a causative factor in Alzheimer's disease: a debatable hypothesis. J Neurochem. 2014; 129:559–572.
44. Ricciarelli R, Canepa E, Marengo B, Marinari UM, Poli G, Pronzato MA, Domenicotti C. Cholesterol and Alzheimer's disease: a still poorly understood correlation. IUBMB Life. 2012; 64:931–935.
45. Gamba P, Testa G, Sottero B, Gargiulo S, Poli G, Leonarduzzi G. The link between altered cholesterol metabolism and Alzheimer's disease. Ann N Y Acad Sci. 2012; 1259:54–64.
46. Dauncey MJ. New insights into nutrition and cognitive neuroscience. Proc Nutr Soc. 2009; 68:408–415.
47. Gardener S, Gu Y, Rainey-Smith SR, Keogh JB, Clifton PM, Mathieson SL, Taddei K, Mondal A, Ward VK, Scarmeas N, et al. Adherence to a Mediterranean diet and Alzheimer's disease risk in an Australian population. Transl Psychiatry. 2012; 2:e164.
48. Otaegui-Arrazola A, Amiano P, Elbusto A, Urdaneta E, Martínez-Lage P. Diet, cognition, and Alzheimer's disease: food for thought. Eur J Nutr. 2014; 53:1–23.
49. Solfrizzi V, Panza F, Frisardi V, Seripa D, Logroscino G, Imbimbo BP, Pilotto A. Diet and Alzheimer's disease risk factors or prevention: the current evidence. Expert Rev Neurother. 2011; 11:677–708.
50. Martínez-Lapiscina EH, Clavero P, Toledo E, Estruch R, Salas-Salvadó J, San Julián B, Sanchez-Tainta A, Ros E, Valls-Pedret C, Martinez-Gonzalez MÁ. Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial. J Neurol Neurosurg Psychiatry. 2013; 84:1318–1325.
51. Orgogozo JM, Dartigues JF, Lafont S, Letenneur L, Commenges D, Salamon R, Renaud S, Breteler MB. Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev Neurol (Paris). 1997; 153:185–192.
52. Kwon KJ, Kim JN, Kim MK, Lee J, Ignarro LJ, Kim HJ, Shin CY, Han SH. Melatonin synergistically increases resveratrol-induced heme oxygenase-1 expression through the inhibition of ubiquitin-dependent proteasome pathway: a possible role in neuroprotection. J Pineal Res. 2011; 50:110–123.
53. Kwon KJ, Kim HJ, Shin CY, Han SH. Melatonin potentiates the neuroprotective properties of resveratrol against beta-amyloid-induced neurodegeneration by modulating AMP-activated protein kinase pathways. J Clin Neurol. 2010; 6:127–137.
54. Fernández-Mar MI, Mateos R, García-Parrilla MC, Puertas B, Cantos-Villar E. Bioactive compounds in wine: resveratrol, hydroxytyrosol and melatonin: a review. Food Chem. 2012; 130:797–813.
55. Pasinetti GM. Novel role of red wine-derived polyphenols in the prevention of Alzheimer's disease dementia and brain pathology: experimental approaches and clinical implications. Planta Med. 2012; 78:1614–1619.
56. Kamphuis PJ, Scheltens P. Can nutrients prevent or delay onset of Alzheimer's disease? J Alzheimers Dis. 2010; 20:765–775.
57. Mi W, van Wijk N, Cansev M, Sijben JW, Kamphuis PJ. Nutritional approaches in the risk reduction and management of Alzheimer's disease. Nutrition. 2013; 29:1080–1089.
58. Wilson RS, Evans DA, Bienias JL, Mendes de Leon CF, Schneider JA, Bennett DA. Proneness to psychological distress is associated with risk of Alzheimer's disease. Neurology. 2003; 61:1479–1485.
59. Ricci S, Fuso A, Ippoliti F, Businaro R. Stress-induced cytokines and neuronal dysfunction in Alzheimer's disease. J Alzheimers Dis. 2012; 28:11–24.
60. McEwen BS. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007; 87:873–904.
61. Ju YE, McLeland JS, Toedebusch CD, Xiong C, Fagan AM, Duntley SP, Morris JC, Holtzman DM. Sleep quality and preclinical Alzheimer disease. JAMA Neurol. 2013; 70:587–593.
62. Xu L, Jiang CQ, Lam TH, Liu B, Jin YL, Zhu T, Zhang WS, Cheng KK, Thomas GN. Short or long sleep duration is associated with memory impairment in older Chinese: the Guangzhou Biobank Cohort Study. Sleep. 2011; 34:575–580.
63. Tworoger SS, Lee S, Schernhammer ES, Grodstein F. The association of self-reported sleep duration, difficulty sleeping, and snoring with cognitive function in older women. Alzheimer Dis Assoc Disord. 2006; 20:41–48.
64. Barnes VA, Treiber FA, Davis H. Impact of Transcendental Meditation on cardiovascular function at rest and during acute stress in adolescents with high normal blood pressure. J Psychosom Res. 2001; 51:597–605.
65. Newberg AB, Serruya M, Wintering N, Moss AS, Reibel D, Monti DA. Meditation and neurodegenerative diseases. Ann N Y Acad Sci. 2014; 1307:112–123.
66. Wells RE, Yeh GY, Kerr CE, Wolkin J, Davis RB, Tan Y, Spaeth R, Wall RB, Walsh J, Kaptchuk TJ, et al. Meditation's impact on default mode network and hippocampus in mild cognitive impairment: a pilot study. Neurosci Lett. 2013; 556:15–19.
67. Marciniak R, Sheardova K, Cermáková P, Hudeček D, Sumec R, Hort J. Effect of meditation on cognitive functions in context of aging and neurodegenerative diseases. Front Behav Neurosci. 2014; 8:17.
68. Seidler A, Bernhardt T, Nienhaus A, Frölich L. Association between the psychosocial network and dementia: a case-control study. J Psychiatr Res. 2003; 37:89–98.
69. Brenowitz WD, Kukull WA, Beresford SA, Monsell SE, Williams EC. Social relationships and risk of incident mild cognitive impairment in US Alzheimer's disease centers. Alzheimer Dis Assoc Disord. 2014; doi: 10.1097/WAD.0000000000000020.
70. Bennett DA, Schneider JA, Tang Y, Arnold SE, Wilson RS. The effect of social networks on the relation between Alzheimer's disease pathology and level of cognitive function in old people: a longitudinal cohort study. Lancet Neurol. 2006; 5:406–412.
71. Glei DA, Landau DA, Goldman N, Chuang YL, Rodríguez G, Weinstein M. Participating in social activities helps preserve cognitive function: an analysis of a longitudinal, population-based study of the elderly. Int J Epidemiol. 2005; 34:864–871.
72. Burgener SC, Yang Y, Gilbert R, Marsh-Yant S. The effects of a multimodal intervention on outcomes of persons with early-stage dementia. Am J Alzheimers Dis Other Demen. 2008; 23:382–394.
73. Wayne PM, Walsh JN, Taylor-Piliae RE, Wells RE, Papp KV, Donovan NJ, Yeh GY. Effect of tai chi on cognitive performance in older adults: systematic review and meta-analysis. J Am Geriatr Soc. 2014; 62:25–39.
74. De Andrade LP, Gobbi LT, Coelho FG, Christofoletti G, Costa JL, Stella F. Benefits of multimodal exercise intervention for postural control and frontal cognitive functions in individuals with Alzheimer's disease: a controlled trial. J Am Geriatr Soc. 2013; 61:1919–1926.
75. Gomez-Pinilla F. The combined effects of exercise and foods in preventing neurological and cognitive disorders. Prev Med. 2011; 52:S75–S80.
76. Burgener SC, Marsh-Yant S, Nega KK. A combined, multimodal intervention for individuals with dementia. Res Gerontol Nurs. 2011; 4:64–75.
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