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  • Review Article
  • Published:

A major role for cardiovascular burden in age-related cognitive decline

Key Points

  • Evidence from multidisciplinary research indicates that vascular risk factors (VRFs) present during young adulthood and mid-life are potential aetiological factors for cognitive decline and dementia in later life

  • Cardiovascular disease and cognitive ageing (such as cognitive decline and dementia) share similar pathogenetic processes such as atherosclerosis and ischaemia

  • VRFs might contribute to the development of neurodegenerative lesions (such as deposition of β-amyloid) in the brain

  • Clinical and subclinical cardiovascular diseases can be linked to cognitive decline and dementia by causing cerebral hypoxia and silent brain lesions

  • Emerging evidence indicates that dementia in advanced age develops after a lifelong sequence of events beginning with exposure to VRFs in youth, followed by heart disease and cerebrovascular disease

  • Current interventional strategies to promote cardiovascular health might be the most promising approach to protect the brain and maintain intact cognitive function in ageing

Abstract

The incidence of dementia and cardiovascular disease (CVD) increases with age. Current evidence supports the role for both atherosclerosis and arteriosclerosis as a common pathophysiological ground for the heart–brain connection in ageing. Cognitive decline and CVDs share many vascular risk factors (VRFs) such as smoking, hypertension, and diabetes mellitus; furthermore, CVDs can contribute to cognitive decline by causing cerebral hypoperfusion, hypoxia, emboli, or infarcts. Mixed dementia, resulting from both cerebrovascular lesions and neurodegeneration, accounts for the majority of dementia cases among very old individuals (≥75 years). An accumulation of multiple VRFs, especially in middle age (40–59 years of age), can substantially increase dementia risk. The suggested declining trend in dementia risk, occurring in parallel with the decreasing incidence of cardiovascular events in high-income countries, supports the role of cardiovascular burden in dementia. Accordingly, strategies to promote cardiovascular health, especially if implemented from early life, might help to delay the onset of dementia. In this Review, we discuss the literature investigating the association of cardiovascular burden with cognitive decline and dementia over the life-course.

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Figure 1: The heart–brain connection in ageing and cognitive decline.

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References

  1. Qiu, C., Kivipelto, M. & von Strauss, E. Epidemiology of Alzheimer's disease: occurrence, determinants, and strategies toward intervention. Dialogues Clin. Neurosci. 11, 111–128 (2009).

    PubMed  PubMed Central  Google Scholar 

  2. Reitz, C., Brayne, C. & Mayeux, R. Epidemiology of Alzheimer disease. Nat. Rev. Neurol. 7, 137–152 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Schneider, J. A., Arvanitakis, Z., Bang, W. & Bennett, D. A. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 69, 2197–2204 (2007).

    Article  PubMed  Google Scholar 

  4. Schneider, J. A., Arvanitakis, Z., Leurgans, S. E. & Bennett, D. A. The neuropathology of probable Alzheimer disease and mild cognitive impairment. Ann. Neurol. 66, 200–208 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Matthews, F. E. et al. Epidemiological pathology of dementia: attributable-risks at death in the Medical Research Council Cognitive Function and Ageing Study. PLoS Med. 6, e1000180 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Yang, Z., Slavin, M. J. & Sachdev, P. S. Dementia in the oldest old. Nat. Rev. Neurol. 9, 382–393 (2013).

    Article  CAS  PubMed  Google Scholar 

  7. Gorelick, P. B. et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42, 2672–2713 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Qiu, C. Preventing Alzheimer's disease by targeting vascular risk factors: hope and gap. J. Alzheimers Dis. 32, 721–731 (2012).

    Article  PubMed  Google Scholar 

  9. Román, G. C., Nash, D. T. & Fillit, H. Translating current knowledge into dementia prevention. Alzheimer Dis. Assoc. Disord. 26, 295–299 (2012).

    Article  PubMed  Google Scholar 

  10. Nyberg, L., Lövdén, M., Riklund, K., Lindenberger, U. & Bäckman, L. Memory aging and brain maintenance. Trends Cogn. Sci. 16, 292–305 (2012).

    Article  PubMed  Google Scholar 

  11. Wolf, P. A. Contributions of the Framingham Heart Study to stroke and dementia epidemiologic research at 60 years. Arch. Neurol. 69, 567–571 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Gelber, R. P., Launer, L. J. & White, L. R. The Honolulu-Asia Aging Study: epidemiologic and neuropathologic research on cognitive impairment. Curr. Alzheimer Res. 9, 664–672 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hofman, A. et al. The Rotterdam Study: 2014 objectives and design update. Eur. J. Epidemiol. 28, 889–926 (2013).

    Article  CAS  PubMed  Google Scholar 

  14. Chaves, P. H., Kuller, L. H., O'Leary, D. H., Manolio, T. A. & Newman, A. B. Subclinical cardiovascular disease in older adults: insights from the Cardiovascular Health Study. Am. J. Geriatr. Cardiol. 13, 137–151 (2004).

    Article  PubMed  Google Scholar 

  15. Fratiglioni, L., Winblad, B. & von Strauss, E. Prevention of Alzheimer's disease and dementia. Major findings from the Kungsholmen Project. Physiol. Behav. 92, 98–104 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Anstey, K. J., Lipnicki, D. M. & Low, L. F. Cholesterol as a risk factor for dementia and cognitive decline: a systematic review of prospective studies with meta-analysis. Am. J. Geriatr. Psychiatry 16, 343–354 (2008).

    Article  PubMed  Google Scholar 

  17. Peters, R. et al. Smoking, dementia and cognitive decline in the elderly, a systematic review. BMC Geriatr. 8, 36 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Lu, F. P., Lin, K. P. & Kuo, H. K. Diabetes and the risk of multi-system aging phenotypes: a systematic review and meta-analysis. PLoS ONE 4, e4144 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Beydoun, M. A. et al. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health 14, 643 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Qiu, C., Winblad, B. & Fratiglioni, L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol. 4, 487–499 (2005).

    Article  PubMed  Google Scholar 

  21. Anstey, K. J., Cherbuin, N., Budge, M. & Young, J. Body mass index in mid-life and late-life as a risk factor for dementia: a meta-analysis of prospective studies. Obes. Rev. 12, e426–e437 (2011).

    Article  CAS  PubMed  Google Scholar 

  22. Novak, V. & Hajjar, I. The relationship between blood pressure and cognitive function. Nat. Rev. Cardiol. 7, 686–698 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Tolppanen, A. M., Solomon, A., Soininen, H. & Kivipelto, M. Midlife vascular risk factors and Alzheimer's disease: evidence from epidemiological studies. J. Alzheimers Dis. 32, 531–540 (2012).

    Article  PubMed  Google Scholar 

  24. Whitmer, R. A., Sidney, S., Selby, J., Johnston, S. C. & Yaffe, K. Midlife cardiovascular risk factors and risk of dementia in late life. Neurology 64, 277–281 (2005).

    Article  CAS  PubMed  Google Scholar 

  25. Qiu, C., Xu, W., Winblad, B. & Fratiglioni, L. Vascular risk profiles for dementia and Alzheimer's disease in very old people: a population-based longitudinal study. J. Alzheimers Dis. 20, 293–300 (2010).

    Article  PubMed  Google Scholar 

  26. Lobo, E. et al. Is there an association between low-to-moderate alcohol consumption and risk of cognitive decline? Am. J. Epidemiol. 172, 708–716 (2010).

    Article  PubMed  Google Scholar 

  27. Sabia, S. et al. Alcohol consumption and cognitive decline in early old age. Neurology 82, 332–339 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Nooyens, A. C., Bueno-de-Mesquita, H. B., van Gelder, B. M., van Boxtel, M. P. & Verschuren, W. M. Consumption of alcoholic beverages and cognitive decline at middle age: the Doetinchem Cohort Study. Br. J. Nutr. 111, 715–723 (2014).

    Article  CAS  PubMed  Google Scholar 

  29. Peters, R., Peters, J., Warner, J., Beckett, N. & Bulpitt, C. Alcohol, dementia and cognitive decline in the elderly: a systematic review. Age Ageing 37, 505–512 (2008).

    Article  PubMed  Google Scholar 

  30. Anstey, K. J., Mack, H. A. & Cherbuin, N. Alcohol consumption as a risk factor for dementia and cognitive decline: meta-analysis of prospective studies. Am. J. Geriatr. Psychiatry 17, 542–555 (2009).

    Article  PubMed  Google Scholar 

  31. Singh, B. et al. Association of Mediterranean diet with mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis. J. Alzheimers Dis. 39, 271–282 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Qiu, C. Epidemiological findings of vascular risk factors in Alzheimer's disease: implications for therapeutic and preventive intervention. Expert Rev. Neurother. 11, 1593–1607 (2011).

    Article  PubMed  Google Scholar 

  33. Shumaker, S. A. et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 291, 2947–2958 (2004).

    Article  CAS  PubMed  Google Scholar 

  34. Llewellyn, D. J. et al. Framingham Stroke Risk Profile and poor cognitive function: a population-based study. BMC Neurol. 8, 12 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kaffashian, S. et al. Predictive utility of the Framingham general cardiovascular disease risk profile for cognitive function: evidence from the Whitehall II study. Eur. Heart J. 32, 2326–2332 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Kaffashian, S. et al. Predicting cognitive decline: a dementia risk score vs. the Framingham vascular risk scores. Neurology 80, 1300–1306 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kaffashian, S. et al. Midlife stroke risk and cognitive decline: a 10-year follow-up of the Whitehall II cohort study. Alzheimers Dement. 9, 572–579 (2013).

    Article  PubMed  Google Scholar 

  38. Dregan, A., Stewart, R. & Gulliford, M. C. Cardiovascular risk factors and cognitive decline in adults aged 50 and over: a population-based cohort study. Age Ageing 42, 338–345 (2013).

    Article  PubMed  Google Scholar 

  39. Yaffe, K. et al. Early adult to mid-life cardiovascular risk factors and cognitive function. Circulation 129, 1560–1567 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Anstey, K. J., Sargent-Cox, K., Garde, E., Cherbuin, N. & Butterworth, P. Cognitive development over 8 years in mid-life and its association with cardiovascular risk factors. Neuropsychology 28, 653–665 (2014).

    Article  PubMed  Google Scholar 

  41. Unverzagt, F. W. et al. Vascular risk factors and cognitive impairment in a stroke-free cohort. Neurology 77, 1729–1736 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Joosten, H. et al. Cardiovascular risk profile and cognitive function in young, middle-aged, and elderly subjects. Stroke 44, 1543–1549 (2013).

    Article  CAS  PubMed  Google Scholar 

  43. Virta, J. J. et al. Midlife cardiovascular risk factors and late cognitive impairment. Eur. J. Epidemiol. 28, 405–416 (2013).

    Article  PubMed  Google Scholar 

  44. Laughlin, G. A. et al. Sex differences in the association of Framingham Cardiac Risk Score with cognitive decline in community-dwelling elders without clinical heart disease. Psychosom. Med. 73, 683–689 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Warsch, J. R. et al. Association between northern Manhattan study global vascular risk score and successful aging. J. Am. Geriatr. Soc. 61, 519–524 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Zeki Al Hazzouri, A. et al. Cardiovascular risk score, cognitive decline, and dementia in older Mexican Americans: the role of sex and education. J. Am. Heart Assoc. 2, e004978 (2013).

    PubMed  Google Scholar 

  47. Crichton, G. E., Elias, M. F., Davey, A. & Alkerwi, A. Cardiovascular health and cognitive function: the Maine-Syracuse Longitudinal Study. PLoS ONE 9, e89317 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Thacker, E. L. et al. The American Heart Association Life's Simple 7 and incident cognitive impairment: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. J. Am. Heart Assoc. 3, e000635 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Barnes, D. E. & Yaffe, K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol. 10, 819–828 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Karmali, K. N. & Lloyd-Jones, D. M. Adding a life-course perspective to cardiovascular-risk communication. Nat. Rev. Cardiol. 10, 111–115 (2013).

    Article  PubMed  Google Scholar 

  51. Barnes, D. E. et al. Predicting risk of dementia in older adults: the late-life dementia risk index. Neurology 73, 173–179 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Reitz, C. et al. A summary risk score for the prediction of Alzheimer disease in elderly persons. Arch. Neurol. 67, 835–841 (2010).

    PubMed  PubMed Central  Google Scholar 

  53. Exalto, L. G. et al. Risk score for prediction of 10 year dementia risk in individuals with type 2 diabetes: a cohort study. Lancet Diabetes Endocrinol. 1, 183–190 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Anstey, K. J. et al. A self-report risk index to predict occurrence of dementia in three independent cohorts of older adults: the ANU-ADRI. PLoS ONE 9, e86141 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kivipelto, M. et al. Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol. 5, 735–741 (2006).

    Article  PubMed  Google Scholar 

  56. Exalto, L. G. et al. Midlife risk score for the prediction of dementia four decades later. Alzheimers Dement. 10, 562–570 (2014).

    Article  PubMed  Google Scholar 

  57. Kivipelto, M. et al. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): study design and progress. Alzheimers Dement. 9, 657–665 (2013).

    Article  PubMed  Google Scholar 

  58. Bursi, F. et al. Heart disease and dementia: a population-based study. Am. J. Epidemiol. 163, 135–141 (2006).

    Article  PubMed  Google Scholar 

  59. Rusanen, M. et al. Heart diseases and long-term risk of dementia and Alzheimer's disease: a population-based CAIDE study. J. Alzheimers Dis. 42, 183–191 (2014).

    Article  PubMed  Google Scholar 

  60. Newman, A. B. et al. Dementia and Alzheimer's disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort. J. Am. Geriatr. Soc. 53, 1101–1107 (2005).

    Article  PubMed  Google Scholar 

  61. Rosano, C. & Newman, A. B. Cardiovascular disease and risk of Alzheimer's disease. Neurol. Res. 28, 612–620 (2006).

    Article  PubMed  Google Scholar 

  62. Haring, B. et al. Cardiovascular disease and cognitive decline in postmenopausal women: results from the Women's Health Initiative Memory Study. J. Am. Heart. Assoc. 2, e000369 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Eriksson, U. K., Bennet, A. M., Gatz, M., Dickman, P. W. & Pedersen, N. L. Nonstroke cardiovascular disease and risk of Alzheimer disease and dementia. Alzheimer Dis. Assoc. Disord. 24, 213–219 (2010).

    PubMed  PubMed Central  Google Scholar 

  64. Ikram, M. A. et al. Unrecognized myocardial infarction in relation to risk of dementia and cerebral small vessel disease. Stroke 39, 1421–1426 (2008).

    Article  PubMed  Google Scholar 

  65. Singh-Manoux, A. et al. History of coronary heart disease and cognitive performance in mid-life: the Whitehall II study. Eur. Heart J. 29, 2100–2107 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Roberts, R. O. et al. Coronary heart disease is associated with non-amnestic mild cognitive impairment. Neurobiol. Aging 31, 1894–1902 (2010).

    Article  PubMed  Google Scholar 

  67. Roberts, R. O. et al. Cardiac disease associated with increased risk of nonamnestic cognitive impairment: stronger effect on women. JAMA Neurol. 70, 374–382 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Eggermont, L. H. et al. Cardiac disease and cognitive impairment: a systematic review. Heart 98, 1334–1340 (2012).

    Article  PubMed  Google Scholar 

  69. Rostamian, S. et al. Cognitive impairment and risk of stroke: a systematic review and meta-analysis of prospective cohort studies. Stroke 45, 1342–1348 (2014).

    Article  PubMed  Google Scholar 

  70. Tolppanen, A. M. et al. Incident ischaemic heart disease in persons with Alzheimer's disease in a Finnish nationwide exposure-matched cohort. Int. J. Cardiol. 170, 195–201 (2013).

    Article  PubMed  Google Scholar 

  71. Singh-Manoux, A. et al. Cognition and incident coronary heart disease in late mid-life: the Whitehall II study. Intelligence 37, 529–534 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Nordström, P., Religa, D., Wimo, A., Winblad, B. & Eriksdotter, M. The use of cholinesterase inhibitors and the risk of myocardial infarction and death: a nationwide cohort study in subjects with Alzheimer's disease. Eur. Heart J. 34, 2585–2591 (2013).

    Article  CAS  PubMed  Google Scholar 

  73. ONTARGET Investigators, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N. Engl. J. Med. 358, 1547–1559 (2008).

  74. Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomized controlled trial. Lancet 372, 1174–1183 (2008).

  75. O'Donnell, M. et al. Cognitive impairment and risk of cardiovascular events and mortality. Eur. Heart J. 33, 1777–1786 (2012).

    Article  PubMed  Google Scholar 

  76. Kwok, C. S., Loke, Y. K., Hale, R., Potter, J. F. & Myint, P. K. Atrial fibrillation and incidence of dementia: a systematic review and meta-analysis. Neurology 76, 914–922 (2011).

    Article  CAS  PubMed  Google Scholar 

  77. Santangeli, P. et al. Atrial fibrillation and the risk of incident dementia: a meta-analysis. Heart Rhythm. 9, 1761–1768 (2012).

    Article  PubMed  Google Scholar 

  78. Kalantarian, S., Stern, T. A., Mansour, M. & Ruskin, J. N. Cognitive impairment associated with atrial fibrillation: a meta-analysis. Ann. Intern. Med. 158, 338–346 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Udompanich, S., Lip, G. Y., Apostolakis, S. & Lane, D. A. Atrial fibrillation as a risk factor for cognitive impairment: a semi-systematic review. QJM 106, 795–802 (2013).

    Article  CAS  PubMed  Google Scholar 

  80. Stefansdottir, H. et al. Atrial fibrillation is associated with reduced brain volume and cognitive function independent of cerebral infarcts. Stroke 44, 1020–1025 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Thacker, E. L. et al. Atrial fibrillation and cognitive decline: a longitudinal cohort study. Neurology 81, 119–125 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Marzona, I. et al. Increased risk of cognitive and functional decline in patients with atrial fibrillation: results of the ONTARGET and TRANSCEND studies. CMAJ 184, E329–E336 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  83. Gure, T. R. et al. Prevalence of cognitive impairment in older adults with heart failure. J. Am. Geriatr. Soc. 60, 1724–1729 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Hajduk, A. M. et al. Cognitive change in heart failure: a systematic review. Circ. Cardiovasc. Qual. Outcomes 6, 451–460 (2013).

    Article  PubMed  Google Scholar 

  85. Heckman, G. A. et al. Heart failure and cognitive impairment: challenges and opportunities. Clin. Interv. Aging. 2, 209–218 (2007).

    PubMed  PubMed Central  Google Scholar 

  86. Ganguli, M., Fu, B., Snitz, B. E., Hughes, T. F. & Chang, C. C. Mild cognitive impairment: incidence and vascular risk factors in a population-based cohort. Neurology 80, 2112–2120 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Vogels, R. L., Scheltens, P., Schroeder-Tanka, J. M. & Weinstein, H. C. Cognitive impairment in heart failure: a systematic review of the literature. Eur. J. Heart Fail. 9, 440–449 (2007).

    Article  PubMed  Google Scholar 

  88. Pressler, S. J. Cognitive functioning and chronic heart failure: a review of the literature (2002–July 2007). J. Cardiovasc. Nurs. 23, 239–249 (2008).

    Article  PubMed  Google Scholar 

  89. Jefferson, A. L. et al. Cardiac index is associated with brain aging: the Framingham Heart Study. Circulation 122, 690–697 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Jefferson, A. L. et al. Relation of left ventricular ejection fraction to cognitive aging (from the Framingham Heart Study). Am. J. Cardiol. 108, 1346–1351 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Viles-Gonzalez, J. F., Fuster, V. & Badimon, J. J. Atherothrombosis: a widespread disease with unpredictable and life-threatening consequences. Eur. Heart J. 25, 1197–1207 (2004).

    Article  CAS  PubMed  Google Scholar 

  92. van Oijen, M. et al. Atherosclerosis and risk for dementia. Ann. Neurol. 61, 403–410 (2007).

    Article  PubMed  Google Scholar 

  93. Laurin, D., Masaki, K. H., White, L. R. & Launer, L. J. Ankle-to-brachial index and dementia: the Honolulu-Asia Aging Study. Circulation 116, 2269–2274 (2007).

    Article  PubMed  Google Scholar 

  94. Guerchet, M. et al. Ankle-brachial index as a marker of cognitive impairment and dementia in general population: a systematic review. Atherosclerosis 216, 251–257 (2011).

    Article  CAS  PubMed  Google Scholar 

  95. Guerchet, M. et al. Association between a low ankle-brachial index and dementia in a general elderly population in Central Africa (Epidemiology of Dementia in Central Africa Study). J. Am. Geriatr. Soc. 61, 1135–1140 (2013).

    Article  PubMed  Google Scholar 

  96. Laukka, E. J., Starr, J. M. & Deary, I. J. Lower ankle-brachial index is related to worse cognitive performance in old age. Neuropsychology 28, 281–289 (2014).

    Article  PubMed  Google Scholar 

  97. Hofman, A. et al. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet 349, 151–154 (1997).

    Article  CAS  PubMed  Google Scholar 

  98. Arntzen, K. A. et al. Carotid atherosclerosis predicts lower cognitive test results: a 7-year follow-up study of 4, 371 stroke-free subjects - the Tromsø study. Cerebrovasc. Dis. 33, 159–165 (2012).

    Article  PubMed  Google Scholar 

  99. Zhong, W. et al. Carotid atherosclerosis and 10-year changes in cognitive function. Atherosclerosis 224, 506–510 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Romero, J. R. et al. Carotid artery atherosclerosis, MRI indices of brain ischemia, aging, and cognitive impairment: the Framingham study. Stroke 40, 1590–1596 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  101. Chang, X. L. et al. Association between asymptomatic carotid stenosis and cognitive function: a systematic review. Neurosci. Biobehav. Rev. 37, 493–499 (2013).

    Article  Google Scholar 

  102. Balestrini, S. et al. Severe carotid stenosis and impaired cerebral hemodynamics can influence cognitive deterioration. Neurology 80, 2145–2150 (2013).

    Article  PubMed  Google Scholar 

  103. Franklin, S. S. Beyond blood pressure: arterial stiffness as a new biomarker of cardiovascular disease. J. Am. Soc. Hypertens. 2, 140–151 (2008).

    Article  PubMed  Google Scholar 

  104. Poels, M. M. et al. Arterial stiffness, cognitive decline, and risk of dementia: the Rotterdam study. Stroke 38, 888–892 (2007).

    Article  PubMed  Google Scholar 

  105. Elias, M. F. et al. Arterial pulse wave velocity and cognition with advancing age. Hypertension 53, 668–673 (2009).

    Article  CAS  PubMed  Google Scholar 

  106. Tsao, C. W. et al. Relations of arterial stiffness and endothelial function to brain aging in the community. Neurology 81, 984–991 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  107. Waldstein, S. R. et al. Pulse pressure and pulse wave velocity are related to cognitive decline in the Baltimore Longitudinal Study of Aging. Hypertension 51, 99–104 (2008).

    Article  CAS  PubMed  Google Scholar 

  108. Zeki Al Hazzouri, A. et al. Pulse wave velocity and cognitive decline in elders: the Health, Aging, and Body Composition study. Stroke 44, 388–393 (2013).

    Article  PubMed  Google Scholar 

  109. Watson, N. L. et al. Arterial stiffness and cognitive decline in well-functioning older adults. J. Gerontol. A. Biol. Sci. Med. Sci. 66, 1336–1342 (2011).

    Article  PubMed  Google Scholar 

  110. Singer, J. et al. Arterial stiffness, the brain and cognition: a systematic review. Ageing Res. Rev. 15, 16–27 (2014).

    Article  PubMed  Google Scholar 

  111. Elias-Smale, S. E. et al. Coronary calcium score improves classification of coronary heart disease risk in the elderly: the Rotterdam study. J. Am. Coll. Cardiol. 56, 1407–1414 (2010).

    Article  PubMed  Google Scholar 

  112. Rosano, C., Naydeck, B., Kuller, L. H., Longstreth, W. T. Jr. & Newman, A. B. Coronary artery calcium: associations with brain magnetic resonance imaging abnormalities and cognitive status. J. Am. Geriatr. Soc. 53, 609–615 (2005).

    Article  PubMed  Google Scholar 

  113. Vidal, J. S. et al. Coronary artery calcium, brain function and structure: the AGES-Reykjavik Study. Stroke 41, 891–897 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  114. Bos, D. et al. Atherosclerotic calcification relates to cognitive function and to brain changes on magnetic resonance imaging. Alzheimers Dement. 8, S104–S111 (2012).

    Article  CAS  PubMed  Google Scholar 

  115. Dadu, R. T. et al. Cardiovascular biomarkers and subclinical brain disease in the atherosclerosis risk in communities study. Stroke 44, 1803–1808 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Schneider, A. L. et al. High-sensitivity cardiac troponin T and cognitive function and dementia risk: the atherosclerosis risk in communities study. Eur. Heart J. 35, 1817–1824 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Qiu, C. et al. Microvascular lesions in the brain and retina: The age, gene/environment susceptibility-Reykjavik study. Ann. Neurol. 65, 569–576 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  118. McClintic, B. R., McClintic, J. I., Bisognano, J. D. & Block, R. C. The relationship between retinal microvascular abnormalities and coronary heart disease: a review. Am. J. Med. 123, 374.e1–374.e7 (2010).

    Article  Google Scholar 

  119. Li, L. J., Lee, Y. S., Wong, T. Y. & Cheung, C. Y. Can the retinal microvasculature offer clues to cardiovascular risk factors in early life? Acta Paediatr. 102, 941–946 (2013).

    Article  PubMed  Google Scholar 

  120. Qiu, C. et al. Cerebral microbleeds, retinopathy, and dementia: the AGES-Reykjavik Study. Neurology 75, 2221–2228 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Ikram, M. K., Cheung, C. Y., Wong, T. Y. & Chen, C. P. Retinal pathology as biomarker for cognitive impairment and Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 83, 917–922 (2012).

    Article  PubMed  Google Scholar 

  122. Heringa, S. M. et al. Associations between retinal microvascular changes and dementia, cognitive functioning, and brain imaging abnormalities: a systematic review. J. Cereb. Blood Flow Metab. 33, 983–995 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Selnes, O. A. et al. Cognitive and neurologic outcomes after coronary-artery bypass surgery. N. Engl. J. Med. 366, 250–257 (2012).

    Article  CAS  PubMed  Google Scholar 

  124. Kennedy, E. D. et al. Cognitive outcome after on- and off-pump coronary artery bypass grafting surgery: a systematic review and meta-analysis. J. Cardiothorac. Vasc. Anesth. 27, 253–265 (2013).

    Article  PubMed  Google Scholar 

  125. Muqtadar, H., Testai, F. D. & Gorelick, P. B. The dementia of cardiac disease. Curr. Cardiol. Rep. 14, 732–740 (2012).

    Article  PubMed  Google Scholar 

  126. Schwarz, N. et al. Cognitive decline and ischemic microlesions after coronary catheterization. A comparison to coronary artery bypass grafting. Am. Heart J. 162, 756–763 (2011).

    Article  PubMed  Google Scholar 

  127. Gold, G. et al. Identification of Alzheimer and vascular lesion thresholds for mixed dementia. Brain 130, 2830–2836 (2007).

    Article  PubMed  Google Scholar 

  128. Boyle, P. A. et al. Much of late life cognitive decline is not due to common neurodegenerative pathologies. Ann. Neurol. 74, 478–489 (2013).

    Article  PubMed  Google Scholar 

  129. Kalaria, R. N. Cerebrovascular disease and mechanisms of cognitive impairment: evidence from clinicopathological studies in humans. Stroke 43, 2526–2534 (2012).

    Article  PubMed  Google Scholar 

  130. Pantoni, L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 9, 689–701 (2010).

    Article  PubMed  Google Scholar 

  131. Brundel, M., de Bresser, J., van Dillen, J. J., Kappelle, L. J. & Biessels, G. J. Cerebral microinfarcts: a systematic review of neuropathological studies. J. Cereb. Blood Flow Metab. 32, 425–436 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  132. Lawrence, A. J., Chung, A. W., Morris, R. G., Markus, H. S. & Barrick, T. R. Structural network efficiency is associated with cognitive impairment in small-vessel disease. Neurology 83, 304–311 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Pase, M. P. Modifiable vascular markers for cognitive decline and dementia: the importance of arterial aging and hemodynamic factors. J. Alzheimers Dis. 32, 653–663 (2012).

    Article  PubMed  Google Scholar 

  134. Richardson, K. et al. The neuropathology of vascular disease in the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Curr. Alzheimer Res. 9, 687–696 (2012).

    Article  CAS  PubMed  Google Scholar 

  135. Knopman, D. S. et al. Vascular risk factors and longitudinal changes on brain MRI: the ARIC study. Neurology 76, 1879–1885 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Shah, N. S. et al. Midlife blood pressure, plasma β-amyloid, and the risk for Alzheimer disease: the Honolulu Asia Aging Study. Hypertension 59, 780–786 (2012).

    Article  CAS  PubMed  Google Scholar 

  137. Rodrigue, K. M. et al. Risk factors for β-amyloid deposition in healthy aging: vascular and genetic effects. JAMA Neurol. 70, 600–606 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  138. Qiu, C. et al. Diabetes, markers of brain pathology and cognitive function: the age, gene/environment susceptibility-Reykjavik Study. Ann. Neurol. 75, 138–146 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  139. Cardenas, V. A. et al. Associations among vascular risk factors, carotid atherosclerosis, and cortical volume and thickness in older adults. Stroke 43, 2865–2870 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  140. Reed, B. R. et al. Coronary risk correlates with cerebral amyloid deposition. Neurobiol. Aging 33, 1979–1987 (2012).

    Article  CAS  PubMed  Google Scholar 

  141. Villeneuve, S. et al. Vascular risk and Aβ interact to reduce cortical thickness in AD vulnerable brain regions. Neurology 83, 40–47 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  142. Dublin, S. et al. Neuropathologic changes associated with atrial fibrillation in a population-based autopsy cohort. J. Gerontol. A. Biol. Sci. Med. Sci. 69, 609–615 (2014).

    Article  PubMed  Google Scholar 

  143. Attems, J. & Jellinger, K. A. The overlap between vascular disease and Alzheimer's disease—lessons from pathology. BMC Med. 12, 206 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  144. Yarchoan, M. et al. Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias. Brain 135, 3749–3756 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  145. Dolan, H. et al. Atherosclerosis, dementia, and Alzheimer disease in the Baltimore Longitudinal Study of Aging cohort. Ann. Neurol. 68, 231–240 (2010).

    PubMed  PubMed Central  Google Scholar 

  146. Zheng, L. et al. Cerebral atherosclerosis is associated with cystic infarcts and microinfarcts but not Alzheimer pathologic changes. Stroke 44, 2835–2841 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  147. Casserly, I. & Topol, E. Convergence of atherosclerosis and Alzheimer's disease: inflammation, cholesterol, and misfolded proteins. Lancet 363, 1139–1146 (2004).

    Article  CAS  PubMed  Google Scholar 

  148. Strozyk, D. et al. Contribution of vascular pathology to the clinical expression of dementia. Neurobiol. Aging 31, 1710–1720 (2010).

    Article  PubMed  Google Scholar 

  149. Henskens, L. H. et al. Increased aortic pulse wave velocity is associated with silent cerebral small-vessel disease in hypertensive patients. Hypertension 52, 1120–1126 (2008).

    Article  CAS  PubMed  Google Scholar 

  150. Mitchell, G. F. et al. Arterial stiffness, pressure and flow pulsatility and brain structure and function: The age, gene/environment susceptibility-Reykjavik study. Brain 134, 3398–3407 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Hassell, M. E. et al. Silent cerebral infarcts associated with cardiac disease and procedures. Nat. Rev. Cardiol. 10, 696–706 (2013).

    Article  CAS  PubMed  Google Scholar 

  152. Chen, L. Y. et al. Atrial fibrillation and cognitive decline-the role of subclinical cerebral infarcts: the atherosclerosis risk in communities study. Stroke 45, 2568–2574 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  153. Rahman, F., Kwan, G. F. & Benjamin, E. J. Global epidemiology of atrial fibrillation. Nat. Rev. Cardiol. 11, 639–654 (2014).

    Article  PubMed  Google Scholar 

  154. Whalley, L. J., Dick, F. D. & McNeill, G. A life-course approach to the aetiology of late-onset dementias. Lancet Neurol. 5, 87–96 (2006).

    Article  PubMed  Google Scholar 

  155. DeCarli, C. Assessing the brain as an end-organ of vascular disease. Nat. Rev. Cardiol. 9, 435–436 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  156. Goldenberg, I. et al. Cumulative burden of atherosclerotic risk genotypes and the age at onset of a first myocardial infarction: a case-only carriership approach. Ann. Noninvasive Electrocardiol. 13, 287–294 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  157. Shiue, I. Age of onset for stroke delayed in the 21st century: what is next? Clin. Neurol. Neurosurg. 113, 725–726 (2011).

    Article  PubMed  Google Scholar 

  158. Matthews, F., Brayne, C. & Medical Research Council Cognitive Function and Ageing Study Investigators. The incidence of dementia in England and Wales: findings from the five identical sites of the MRC CFA Study. PLoS Med. 2, e193 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  159. Tzourio, C. 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. 163, 1069–1075 (2003).

    Article  CAS  PubMed  Google Scholar 

  160. Willis, K. J. & Hakim, A. M. Stroke prevention and cognitive reserve: emerging approaches to modifying risk and delaying onset of dementia. Front. Neurol. 4, 13 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  161. Mearns, B. M. & Fuster, V. Highlight dementia risk to reduce CVD. Nat. Rev. Cardiol. 7, 237 (2010).

    Article  PubMed  Google Scholar 

  162. Brookmeyer, R., Johnson, E., Ziegler-Graham, K. & Arrighi, H. M. Forecasting the global burden of Alzheimer's disease. Alzheimers Dement. 3, 186–191 (2007).

    Article  PubMed  Google Scholar 

  163. Solomon, A. et al. Advances in the prevention of Alzheimer's disease and dementia. J. Intern. Med. 275, 229–250 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Rocca, W. A. et al. Trends in the incidence and prevalence of Alzheimer's disease, dementia, and cognitive impairment in the United States. Alzheimers Dement. 7, 80–93 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Wiberg, P., Waern, M., Billstedt, E., Ostling, S. & Skoog, I. Secular trends in the prevalence of dementia and depression in Swedish septuagenarians 1976–2006. Psychol. Med. 43, 2627–2634 (2013).

    Article  CAS  PubMed  Google Scholar 

  166. Matthews, F. E. 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 382, 1405–1412 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  167. Schrijvers, E. M. et al. Is dementia incidence declining? Trends in dementia incidence since 1990 in the Rotterdam Study. Neurology 78, 1456–1463 (2012).

    Article  CAS  PubMed  Google Scholar 

  168. Qiu, C., von Strauss, E., Bäckman, L., Winblad, B. & Fratiglioni, L. Twenty-year changes in dementia occurrence suggest decreasing incidence in central Stockholm, Sweden. Neurology 80, 1888–1894 (2013).

    Article  PubMed  Google Scholar 

  169. Jones, D. S. & Greene, J. A. The decline and rise of coronary heart disease: understanding public health catastrophism. Am. J. Public. Health. 103, 1207–1218 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  170. Chan, K. Y. et al. Epidemiology of Alzheimer's disease and other forms of dementia in China, 1990–2010: a systematic review and analysis. Lancet 381, 2016–2023 (2013).

    Article  PubMed  Google Scholar 

  171. Yang, G. et al. Rapid health transition in China, 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet 381, 1987–2015 (2010).

    Article  Google Scholar 

  172. Liang, Y., Liu, R., Du, S. & Qiu, C. Trends in incidence of hypertension in Chinese adults, 1991–2009: The China Health and Nutrition Survey. Int. J. Cardiol. 175, 96–101 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors' work was supported by grants from the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, and the Karolinska Institutet, Stockholm, Sweden.

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C.Q. researched data for the article. Both authors contributed substantially to discussion of its content, and to writing, reviewing, and editing the manuscript before submission.

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Correspondence to Chengxuan Qiu.

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Qiu, C., Fratiglioni, L. A major role for cardiovascular burden in age-related cognitive decline. Nat Rev Cardiol 12, 267–277 (2015). https://doi.org/10.1038/nrcardio.2014.223

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