Lifestyle Factors in the Prevention of Dementia: A Life Course Perspective

  • Chengxuan QiuEmail author
Part of the International Perspectives on Aging book series (Int. Perspect. Aging, volume 10)


Dementia affects more than 36 million people worldwide. As a major cause of late-life functional dependence, institutionalization, poor quality of life, and mortality, dementia has posed a tremendous threat to public health and healthcare systems in both high- and middle-income countries. Preventing or postponing the onset of dementia by targeting major modifiable risk factors will significantly reduce the individual and societal burden of the disease. Dementia is a multifactorial disorder, in which the risk of dementia is determined by biological/genetic factors, environmental factors, and their interactions experienced over the lifespan. In the last two decades, a growing body of evidence from multidisciplinary research has suggested that lifestyle and metabolic risk factors (e.g., smoking, excessive alcohol consumption, physical inactivity, obesity, hypertension, diabetes, and hyperlipidemia) are involved in the development and progression of dementia. In particular, from a life course perspective, systematic reviews and meta-analyses of prospective studies have revealed the age-dependent association of dementia with major metabolic factors such as hypertension, obesity, and high cholesterol, i.e., possessing these factors in midlife, but not necessarily in late life, is associated with increased risk of dementia. The biological plausibility for lifestyle or metabolic risk factors to be involved in the pathogenesis and clinical expression of dementia is partly supported by neuroimaging and neuropathological studies. This has significant implications for developing intervention strategies against dementia, i.e., the multifactorial nature of dementia and the proper time-window over the lifespan for intervention should be taken into account in the future when designing preventative programs against this devastating disorder.


Alzheimer Dementia Metabolic Risk Factor Cardiometabolic Risk Factor Dementia Risk Dementia Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by the European Program Future Leaders of Ageing Research in Europe (FLARE), coordinated by the European Research Area in Ageing (ERA-AGE). Dr. C. Qiu was supported in part by the Swedish Council for Working Life and Social Research (FAS), Swedish Research Council (VR), Swedish Brain Power, and Karolinska Institute, Stockholm, Sweden. I would like to thank Dr. Yajun Liang for providing thoughtful comments on this chapter.


  1. Ancelin ML, Carrière I, Barberger-Gateau P et al (2012) Lipid lowering agents, cognitive decline, and dementia: the Three-City Study. J Alzheimers Dis 30:629–637Google Scholar
  2. Anstey KJ, von Sanden C, Salim A, O’Kearney R (2007) Smoking as a risk factor for dementia and cognitive decline: a meta-analysis of prospective studies. Am J Epidemiol 166:367–378CrossRefGoogle Scholar
  3. Anstey KJ, Lipnicki DM, Low LF (2008) Cholesterol as a risk factor for dementia and cognitive decline: a systematic review of prospective studies with meta-analysis. Am J Geriatr Psychiatry 16:343–354CrossRefGoogle Scholar
  4. Anstey KJ, Mack HA, Cherbuin N (2009) Alcohol consumption as a risk factor for dementia and cognitive decline: meta-analysis of prospective studies. Am J Geriatr Psychiatry 17:542–555CrossRefGoogle Scholar
  5. Anstey KJ, Cherbuin N, Budge M, Young J (2011) Body mass index in midlife and late-life as a risk factor for dementia: a meta-analysis of prospective studies. Obes Rev 12:e426–e437CrossRefGoogle Scholar
  6. Arvanitakis Z, Leurgans SE, Barnes LL et al (2011) Microinfarct pathology, dementia, and cognitive systems. Stroke 42:722–727CrossRefGoogle Scholar
  7. Barnes DE, Yaffe K (2011) The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol 10:819–828CrossRefGoogle Scholar
  8. Barnes DE, Covinsky K, Whitmer RA et al (2009) Predicting risk of dementia in older adults: the late-life dementia risk index. Neurology 73:173–179CrossRefGoogle Scholar
  9. Beydoun MA, Beydoun HA, Wang Y (2008) Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis. Obes Rev 9: 204–218CrossRefGoogle Scholar
  10. Bowen ME (2012) A prospective examination of the relationship between physical activity and dementia risk in later life. Am J Health Promot 26:333–340CrossRefGoogle Scholar
  11. Brodaty H, Breteler MM, Dekosky ST et al (2011) The world of dementia beyond 2020. J Am Geriatr Soc 59:923–927CrossRefGoogle Scholar
  12. Buchman AS, Boyle PA, Yu L et al (2012) Total daily physical activity and the risk of AD and cognitive decline in older adults. Neurology 78:1323–1329CrossRefGoogle Scholar
  13. Casserly I, Topol E (2004) Convergence of atherosclerosis and Alzheimer’s disease: inflammation, cholesterol, and misfolded proteins. Lancet 363:1139–1146CrossRefGoogle Scholar
  14. Cataldo JK, Prochaska JJ, Glantz SA (2010) Cigarette smoking is a risk factor for Alzheimer’s disease: an analysis controlling for tobacco industry affiliation. J Alzheimers Dis 19:465–480Google Scholar
  15. Chan KY, Wang W, Wu JJ et al (2013) Epidemiology of Alzheimer’s disease and other forms of dementia in China, 1990-2010: a systematic review and analysis. Lancet 381:2016–2023CrossRefGoogle Scholar
  16. Chen R (2012) Association of environmental tobacco smoke with dementia and Alzheimer’s disease among never smokers. Alzheimers Dement 8:590–595CrossRefGoogle Scholar
  17. Cheng G, Huang C, Deng H, Wang H (2012) Diabetes as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies. Intern Med J 42:484–491CrossRefGoogle Scholar
  18. Crane PK, Walker R, Hubbard RA (2013) Glucose levels and risk of dementia. N Engl J Med 369:540–548CrossRefGoogle Scholar
  19. Dahl Aslan A (2014) Obesity, cognitive ageing, and dementia: the usefulness of longitudinal studies to understand the obesity paradox. In: Leist AK, Kulmala J (eds) Health and cognition in old age. Springer, New YorkGoogle Scholar
  20. Debette S, Seshadri S, Beiser A et al (2011) Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline. Neurology 77:461–468CrossRefGoogle Scholar
  21. Dolan H, Crain B, Troncoso J et al (2010) Atherosclerosis, dementia, and Alzheimer’s disease in the BLSA cohort. Ann Neurol 68:231–240Google Scholar
  22. Duron E, Hanon O (2010) Antihypertensive treatments, cognitive decline, and dementia. J Alzheimers Dis 20:903–914Google Scholar
  23. Exalto LG, Quesenberry CP, Barnes D et al (2013) Midlife risk score for the prediction of dementia four decades later. Alzheimers Dement. pii: S1552-5260(13)02465-5Google Scholar
  24. Feldman HH, Doody RS, Kivipelto M et al (2010) Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology 74:956–964CrossRefGoogle Scholar
  25. Fitzpatrick AL, Kuller LH, Lopez OL et al (2009) Midlife and late-life obesity and the risk of dementia: the Cardiovascular Health Study. Arch Neurol 66:336–342CrossRefGoogle Scholar
  26. Forti P, Pisacane N, Rietti E et al (2010) Metabolic syndrome and risk of dementia in older adults. J Am Geriatr Soc 58:487–492CrossRefGoogle Scholar
  27. Fratiglioni L, Qiu C (2013) Epidemiology of dementia. In: Dening T, Thomas A (eds) The Oxford textbook of old age psychiatry, 5th edn. Oxford University Press, New York, pp 389–413Google Scholar
  28. Garcia-Alloza M, Gregory J, Kuchibhotla KV et al (2011) Cerebrovascular lesions induce transient β-amyloid deposition. Brain 134:3697–3707CrossRefGoogle Scholar
  29. Gelber RP, Petrovitch H, Masaki KH et al (2012) Lifestyle and the risk of dementia in Japanese-American men. J Am Geriatr Soc 60:118–123CrossRefGoogle Scholar
  30. Gelber RP, Ross GW, Petrovitch H et al (2013) Antihypertensive medication use and risk of cognitive impairment: The Honolulu-Asia Aging Study. Neurology 81:888–895CrossRefGoogle Scholar
  31. Guan JW, Huang CQ, Li YH et al (2011) No association between hypertension and risk for Alzheimer’s disease: a meta-analysis of longitudinal studies. J Alzheimers Dis 27:799–807Google Scholar
  32. Haag MD, Hofman A, Koudstaal PJ et al (2009) Duration of antihypertensive drug use and risk of dementia: a prospective cohort study. Neurology 72:1727–1734CrossRefGoogle Scholar
  33. Hafsteinsdottir SH, Eiriksdottir G, Sigurdsson S et al (2012) Brain tissue volumes by APOE genotype and leisure activity-the AGES-Reykjavik Study. Neurobiol Aging 33:829.e1-8CrossRefGoogle Scholar
  34. Hamer M, Chida Y (2009) Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence. Psychol Med 39:3–11CrossRefGoogle Scholar
  35. Herghelegiu AM, Prada GI (2014) Impact of metabolic control on cognitive function and health-related quality of life in older diabetics. In: Leist AK, Kulmala J (eds) Health and cognition in old age. Springer, New YorkGoogle Scholar
  36. Hoffman LB, Schmeidler J, Lesser GT et al (2009) Less Alzheimer disease neuropathology in medicated hypertensive than nonhypertensive persons. Neurology 72:1720–1726CrossRefGoogle Scholar
  37. Jagger C, McKee M, Christensen K et al (2013) Mind the gap–reaching the European target of a 2-year increase in healthy life years in the next decade. Eur J Public Health 23:829–833CrossRefGoogle Scholar
  38. Kalaria RN (2009) Neurodegenerative disease: diabetes, microvascular pathology and Alzheimer disease. Nat Rev Neurol 5:305–306CrossRefGoogle Scholar
  39. Kopf D, Frölich L (2009) Risk of incident Alzheimer’s disease in diabetic patients: a systematic review of prospective trials. J Alzheimers Dis 16:677–685Google Scholar
  40. Launer LJ, Hughes T, Yu B et al (2010) Lowering midlife levels of systolic blood pressure as a public health strategy to reduce late-life dementia: perspective from the Honolulu Heart Program/Honolulu Asia Aging Study. Hypertension 55:1352–1359CrossRefGoogle Scholar
  41. Launer LJ, Hughes TM, White LR (2011) Microinfarcts, brain atrophy, and cognitive function: the Honolulu Asia Aging Study Autopsy Study. Ann Neurol 70:774–780CrossRefGoogle Scholar
  42. Levi Marpillat N, Macquin-Mavier I, Tropeano AI et al (2013) Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis. J Hypertens 31:1073–1082CrossRefGoogle Scholar
  43. Li NC, Lee A, Whitmer RA et al (2010) Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ 340:b5465CrossRefGoogle Scholar
  44. Lin CH, Sheu WH (2013) Hypoglycaemic episodes and risk of dementia in diabetes mellitus: 7-year follow-up study. J Intern Med 273:102–110CrossRefGoogle Scholar
  45. Loef M, Walach H (2013) Midlife obesity and dementia: meta-analysis and adjusted forecast of dementia prevalence in the United States and China. Obesity (Silver Spring) 21:E51–E55CrossRefGoogle Scholar
  46. Lu FP, Lin KP, Kuo HK (2009) Diabetes and the risk of multi-system aging phenotypes: a systematic review and meta-analysis. PLoS One 4:e4144CrossRefGoogle Scholar
  47. Matsuzaki T, Sasaki K, Tanizaki Y et al (2010) Insulin resistance is associated with the pathology of Alzheimer disease: the Hisayama study. Neurology 75:764–770CrossRefGoogle Scholar
  48. Mayeda ER, Haan MN, Kanaya AM et al (2013) Type 2 diabetes and 10-year risk of dementia and cognitive impairment among older Mexican Americans. Diabetes Care 36:2600–2606CrossRefGoogle Scholar
  49. McGuinness B, Craig D, Bullock R, Passmore P (2009a) Statins for the prevention of dementia. Cochrane Database Syst Rev (2):CD003160Google Scholar
  50. McGuinness B, Todd S, Passmore P, Bullock R (2009b) Blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia. Cochrane Database Syst Rev (4):CD004034Google Scholar
  51. McGuinness B, O’Hare J, Craig D et al (2013) Cochrane review on ‘Statins for the treatment of dementia’. Int J Geriatr Psychiatry 28:119–126CrossRefGoogle Scholar
  52. Morgan GS, Gallacher J, Bayer A et al (2012) Physical activity in middle-age and dementia in later life: findings from a prospective cohort of men in Caerphilly, South Wales and a meta-analysis. J Alzheimers Dis 31:569–580Google Scholar
  53. Norton MC, Dew J, Smith H et al (2012) Lifestyle behavior pattern is associated with different levels of risk for incident dementia and Alzheimer’s disease: the Cache County study. J Am Geriatr Soc 60:405–412CrossRefGoogle Scholar
  54. Pantoni L (2010) Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 9:689–701CrossRefGoogle Scholar
  55. Peters R, Beckett N, Forette F et al (2008a) 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 7:683–689CrossRefGoogle Scholar
  56. Peters R, Peters J, Warner J et al (2008b) Alcohol, dementia and cognitive decline in the elderly: a systematic review. Age Ageing 37:505–512CrossRefGoogle Scholar
  57. Peters R, Poulter R, Warner J et al (2008c) Smoking, dementia and cognitive decline in the elderly: a systematic review. BMC Geriatr 8:36CrossRefGoogle Scholar
  58. Power MC, Weuve J, Gagne JJ et al (2011) The association between blood pressure and incident Alzheimer disease: a systematic review and meta-analysis. Epidemiology 22:646–659CrossRefGoogle Scholar
  59. Prince M, Acosta D, Ferri CP et al (2012) Dementia incidence and mortality in middle-income countries, and associations with indicators of cognitive reserve: a 10/66 Dementia Research Group population-based cohort study. Lancet 380:50–58CrossRefGoogle Scholar
  60. Prince M, Bryce R, Albanese E et al (2013) The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 9:63–75CrossRefGoogle Scholar
  61. Profenno LA, Porsteinsson AP, Faraone SV (2010) Meta-analysis of Alzheimer’s disease risk with obesity, diabetes, and related disorders. Biol Psychiatry 67:505–512CrossRefGoogle Scholar
  62. Qiu C (2011) Epidemiological findings of vascular risk factors in Alzheimer’s disease: implications for therapeutic and preventive intervention. Expert Rev Neurother 11:1593–1607CrossRefGoogle Scholar
  63. Qiu C (2012) Preventing Alzheimer’s disease by targeting vascular risk factors: hope and gap. J Alzheimers Dis 32:721–731Google Scholar
  64. Qiu C, Winblad B, Fratiglioni L (2005) The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol 4:487–499CrossRefGoogle Scholar
  65. Qiu C, Cotch MF, Sigurdsson S et al (2010a) Cerebral microbleeds, retinopathy, and dementia: the AGES-Reykjavik Study. Neurology 75:2221–2228CrossRefGoogle Scholar
  66. Qiu C, Sigurdsson S, Zhang Q, et al (2014) Diabetes, markers of brain pathology and cognitive function: the Age, Gene/Environment Susceptibility-Reykjavik Study. Ann Neurol 75:138–146CrossRefGoogle Scholar
  67. Qiu C, Xu W, Fratiglioni L (2010b) Vascular and psychosocial factors for Alzheimer’s disease: epidemiological evidence toward intervention. J Alzheimers Dis 20:689–697Google Scholar
  68. Raffaitin C, Gin H, Empana JP et al (2009) Metabolic syndrome and risk for incident Alzheimer’s disease or vascular dementia: the Three-City Study. Diabetes Care 32:169–174CrossRefGoogle Scholar
  69. Reijmer YD, Leemans A, Brundel M et al (2013) Disruption of the cerebral white matter network is related to slowing of information processing speed in patients with type 2 diabetes. Diabetes 62:2112–2115CrossRefGoogle Scholar
  70. Reitz C, Tang MX, Schupf N et al (2010) A summary risk score for the prediction of Alzheimer disease in elderly persons. Arch Neurol 67:835–841Google Scholar
  71. Reitz C, Brayne C, Mayeux R (2011) Epidemiology of Alzheimer disease. Nat Rev Neurol 7:137–152CrossRefGoogle Scholar
  72. Robine JM, Cambois E, Nusselder W et al (2013) The joint action on healthy life years (JA: EHLEIS). Arch Public Health 71:2CrossRefGoogle Scholar
  73. Rusanen M, Kivipelto M, Quesenberry CP Jr et al (2011) Heavy smoking in midlife and long-term risk of Alzheimer disease and vascular dementia. Arch Intern Med 171:333–339CrossRefGoogle Scholar
  74. Sano M, Bell KL, Galasko D et al (2011) A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology 77:556–563CrossRefGoogle Scholar
  75. Scarmeas N, Luchsinger JA, Schupf N et al (2009) Physical activity, diet, and risk of Alzheimer disease. JAMA 302:627–637CrossRefGoogle Scholar
  76. Schneider JA, Arvanitakis Z, Bang W, Bennett DA (2007) Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 69:2197–2204CrossRefGoogle Scholar
  77. Shepardson NE, Shankar GM, Selkoe DJ (2011) Cholesterol level and statin use in Alzheimer disease: II. Review of human trials and recommendations. Arch Neurol 68:1385–1392CrossRefGoogle Scholar
  78. Smith EE, Schneider JA, Wardlaw JM, Greenberg SM (2012) Cerebral microinfarcts: the invisible lesions. Lancet Neurol 11:272–282CrossRefGoogle Scholar
  79. Staessen JA, Thijs L, Richart T et al (2011) Placebo-controlled trials of blood pressure-lowering therapies for primary prevention of dementia. Hypertension 57:e6–e7CrossRefGoogle Scholar
  80. Stephan BCM (2014) Models for predicting risk of dementia: predictive accuracy and model complexity. In: Leist AK, Kulmala J (eds) Health and cognition in old age. Springer, New YorkGoogle Scholar
  81. Strozyk D, Dickson DW, Lipton RB et al (2010) Contribution of vascular pathology to the clinical expression of dementia. Neurobiol Aging 31:1710–1720CrossRefGoogle Scholar
  82. Tolppanen AM, Lavikainen P, Solomon A et al (2013) History of medically treated diabetes and risk of Alzheimer disease in a nationwide case-control study. Diabetes Care 36:2015–2019CrossRefGoogle Scholar
  83. Vagelatos NT, Eslick GD (2013) Type 2 diabetes as a risk factor for Alzheimer’s disease: the confounders, interactions, and neuropathology associated with this relationship. Epidemiol Rev 35:152–160CrossRefGoogle Scholar
  84. van Elderen SG, de Roos A, de Craen A et al (2010) Progression of brain atrophy and cognitive decline in diabetes mellitus: a 3-year follow-up. Neurology 75:997–1002CrossRefGoogle Scholar
  85. Viswanathan A, Rocca WA, Tzourio C (2009) Vascular risk factors and dementia: how to move forward? Neurology 72:368–374CrossRefGoogle Scholar
  86. Wharton SB, Brayne C, Savva GM et al (2011) Epidemiological neuropathology: the MRC Cognitive Function and Aging Study experience. J Alzheimers Dis 25:359–372Google Scholar
  87. Whitmer RA, Karter AJ, Yaffe K et al (2009) Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 301:1565–1572CrossRefGoogle Scholar
  88. Wimo A, Jönsson L, Bond J et al (2013) The worldwide economic impact of dementia 2010. Alzheimers Dement 9:1–11.e3CrossRefGoogle Scholar
  89. Wong WB, Lin VW, Boudreau D, Devine EB (2013) Statins in the prevention of dementia and Alzheimer’s disease: a meta-analysis of observational studies and an assessment of confounding. Pharmacoepidemiol Drug Saf 22:345–358CrossRefGoogle Scholar
  90. Xu W, Qiu C, Gatz M et al (2009) Mid- and late-life diabetes in relation to the risk of dementia: a population-based twin study. Diabetes 58:71–77CrossRefGoogle Scholar
  91. Yaffe K, Falvey CM, Hamilton N et al (2013) Association between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus. JAMA Intern Med 173:1300–1306CrossRefGoogle Scholar
  92. Yasar S, Xia J, Yao W et al (2013) Antihypertensive drugs decrease risk of Alzheimer disease: Ginkgo Evaluation of Memory Study. Neurology 81:896–903CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Department of Neurobiology, Care Sciences and Society, Aging Research CenterKarolinska Institute-Stockholm UniversityStockholmSweden

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