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Vascular cognitive impairment

Abstract

The term vascular cognitive impairment (VCI) was introduced around the start of the new millennium and refers to the contribution of vascular pathology to any severity of cognitive impairment, ranging from subjective cognitive decline and mild cognitive impairment to dementia. Although vascular pathology is common in elderly individuals with cognitive decline, pure vascular dementia (that is, dementia caused solely by vascular pathology) is uncommon. Indeed, most patients with vascular dementia also have other types of pathology, the most common of which is Alzheimer disease (specifically, the diffuse accumulation of amyloid-β plaques and neurofibrillary tangles composed of tau). At present, the main treatment for VCI is prevention by treating vascular diseases and other risk factors for VCI, such as hypertension and diabetes mellitus. Despite the current paucity of disease-modifying pharmacological treatments, we foresee that eventually, we might be able to target specific brain diseases to prevent cognitive decline and dementia.

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Figure 1: Relationship between VCI and vascular dementia.
Figure 2: Mechanisms of VCI.
Figure 3: Macroscopic and microscopic vascular pathology at autopsy.
Figure 4: MRI manifestations of cerebrovascular disease.

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References

  1. Hachinski, V. C. & Bowler, J. V. Vascular dementia. Neurology 43, 2159–2161 (1993).

    Article  CAS  PubMed  Google Scholar 

  2. Hachinski, V. Vascular dementia: a radical redefinition. Dementia 5, 130–132 (1994).

    CAS  PubMed  Google Scholar 

  3. O'Brien, J. T. et al. Vascular cognitive impairment. Lancet Neurol. 2, 89–98 (2003).

    Article  PubMed  Google Scholar 

  4. 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). This paper provides an overview of the definition, scope and knowledge of VCI.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Román, G. C. et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43, 250–260 (1993).

    Article  PubMed  Google Scholar 

  6. Hejl, A. Potentially reversible conditions in 1000 consecutive memory clinic patients. J. Neurol. Neurosurg. Psychiatry 73, 390–394 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Barker, W. W. et al. Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank. Alzheimer Dis. Assoc. Disord. 16, 203–212 (2002).

    Article  PubMed  Google Scholar 

  8. 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 

  9. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study(MRC CFAS). Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Lancet 357, 169–175 (2001).

    Article  Google Scholar 

  10. Sachdev, P. et al. Diagnostic criteria for vascular cognitive disorders. Alzheimer Dis. Assoc. Disord. 28, 206–218 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 5th edn (American Psychiatric Association, 2013).

  12. Skrobot, O. A. et al. The Vascular Impairment of Cognition Classification Consensus Study. Alzheimers Dement. 13, 624–633 (2016).

    Article  PubMed  Google Scholar 

  13. Skoog, I. in Principles and Practice of Geriatric Psychiatry 3rd edn (eds Abou-Saleh, M. T., Katona, C. L. E. & Kumar, A. ) (Wiley-Blackwell, 2011).

    Google Scholar 

  14. Goodman, R. A. et al. Prevalence of dementia subtypes in United States Medicare fee-for-service beneficiaries, 2011–2013. Alzheimers Dement. 13, 28–37 (2017).

    Article  PubMed  Google Scholar 

  15. Toledo, J. B. et al. Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer's Coordinating Centre. Brain 136, 2697–2706 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Prince, M. et al. The global prevalence of dementia: A systematic review and metaanalysis. Alzheimers Dement. 9, 63–75.e2 (2013).

    Article  PubMed  Google Scholar 

  17. United Nations. World Population Prospects (United Nations, New York, 2013).

  18. Andersson, M. et al. A population-based study on dementia and stroke in 97 year olds. Age Ageing 41, 529–533 (2012).

    Article  PubMed  Google Scholar 

  19. von Strauss, E., Viitanen, M., De Ronchi, D., Winblad, B. & Fratiglioni, L. Aging and the occurrence of dementia: findings from a population-based cohort with a large sample of nonagenarians. Arch. Neurol. 56, 587–592 (1999).

    Article  CAS  PubMed  Google Scholar 

  20. Corraini, P. et al. Long-term risk of dementia among survivors of ischemic or hemorrhagic stroke. Stroke 48, 180–186 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Savva, G. M. et al. Age, neuropathology, and dementia. N. Engl. J. Med. 360, 2302–2309 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. Kua, E. H. et al. The natural history of dementia. Psychogeriatrics 14, 196–201 (2014).

    Article  PubMed  Google Scholar 

  23. Staekenborg, S. S., Pijnenburg, Y. A. L., Lemstra, A. W., Scheltens, P. & van de Flier, W. M. Dementia and rapid mortality: who is at risk? J. Alzheimers Dis. 53, 135–142 (2016).

    Article  PubMed  Google Scholar 

  24. Kim, J. H. et al. Survival in subcortical vascular dementia: predictors and comparison to probable Alzheimer's disease in a tertiary memory clinic population. Dement. Geriatr. Cogn. Disord. 40, 210–221 (2015).

    Article  PubMed  Google Scholar 

  25. Skoog, I. et al. Decreasing prevalence of dementia in 85-year olds examined 22 years apart: the influence of education and stroke. Sci. Rep. 7, 6136 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Khatib, R. et al. Availability and affordability of cardiovascular disease medicines and their effect on use in high-income, middle-income, and low-income countries: an analysis of the PURE study data. Lancet 387, 61–69 (2016).

    Article  PubMed  Google Scholar 

  27. Rizzi, L., Rosset, I. & Roriz-Cruz, M. Global epidemiology of dementia: Alzheimer's and vascular types. Biomed. Res. Int. 2014, 908915 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Ohara, T. et al. Trends in dementia prevalence, incidence, and survival rate in a Japanese community. Neurology 88, 1925–1932 (2017).

    Article  PubMed  Google Scholar 

  29. Zhang, Y. et al. Prevalence of dementia and major dementia subtypes in the Chinese populations: a meta-analysis of dementia prevalence surveys, 1980–2010. J. Clin. Neurosci. 19, 1333–1337 (2012).

    Article  PubMed  Google Scholar 

  30. Satizabal, C. L. et al. Incidence of dementia over three decades in the Framingham Heart Study. N. Engl. J. Med. 374, 523–532 (2016). This study demonstrates a decreased incidence of dementia between the late 1970s and early 2010s. This study also demonstrates a reduction in the risk of dementia in relation to stroke and vascular disorders, such as atrial fibrillation and heart failure, during the study period, suggesting that better treatment of stroke and vascular risk factors can influence the risk of dementia.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wu, Y.-T. et al. The changing prevalence and incidence of dementia over time? Current evidence. Nat. Rev. Neurol. 13, 327–339 (2017).

    Article  PubMed  Google Scholar 

  32. Wu, Y.-T. et al. Dementia in western Europe: epidemiological evidence and implications for policy making. Lancet Neurol. 15, 116–124 (2016).

    Article  CAS  PubMed  Google Scholar 

  33. Feigin, V. L. et al. Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet 383, 245–255 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Sacco, R. L. & Dong, C. Declining stroke incidence and improving survival in US communities. JAMA 312, 237 (2014).

    Article  CAS  PubMed  Google Scholar 

  35. Zhi, X. et al. Prevalence of cardiovascular disorders and risk factors in two 75-year-old birth cohorts examined in 1976–1977 and 2005–2006. Aging Clin. Exp. Res. 25, 377–383 (2013).

    Article  PubMed  Google Scholar 

  36. Lindén, T., Skoog, I., Fagerberg, B., Steen, B. & Blomstrand, C. Cognitive impairment and dementia 20 months after stroke. Neuroepidemiology 23, 45–52 (2004).

    Article  PubMed  Google Scholar 

  37. Portegies, M. L. P. et al. Prestroke vascular pathology and the risk of recurrent stroke and poststroke dementia. Stroke 47, 2119–2122 (2016).

    Article  PubMed  Google Scholar 

  38. Ukraintseva, S., Sloan, F., Arbeev, K. & Yashin, A. Increasing rates of dementia at time of declining mortality from stroke. Stroke 37, 1155–1159 (2006).

    Article  PubMed  Google Scholar 

  39. Farzadfar, F. et al. National, regional, and global trends in serum total cholesterol since 1980: systematic analysis of health examination surveys and epidemiological studies with 321 country-years and 3·0 million participants. Lancet 377, 578–586 (2011).

    Article  PubMed  Google Scholar 

  40. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4·4 million participants. Lancet 387, 1513–1530 (2016).

    Article  Google Scholar 

  41. NCD Risk Factor Collaboration (NCD-RisC).Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet 387, 1377–1396 (2016).

    Article  Google Scholar 

  42. Chugh, S. S. et al. Worldwide Epidemiology of Atrial Fibrillation: a Global Burden of Disease 2010 study. Circulation 129, 837–847 (2014).

    Article  PubMed  Google Scholar 

  43. Kaffashian, S. et al. Long-term clinical impact of vascular brain lesions on magnetic resonance imaging in older adults in the population. Stroke 47, 2865–2869 (2016).

    Article  PubMed  Google Scholar 

  44. Prins, N. D. et al. Cerebral white matter lesions and the risk of dementia. Arch. Neurol. 61, 1531 (2004).

    Article  PubMed  Google Scholar 

  45. Mortamais, M. et al. Spatial Distribution of cerebral white matter lesions predicts progression to mild cognitive impairment and dementia. PLoS ONE 8, e56972 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants. Lancet 389, 37–55 (2017).

    Article  Google Scholar 

  47. Skoog, I. Dementia: Dementia incidence — the times, they are a-changing. Nat. Rev. Neurol. 12, 316–318 (2016).

    Article  PubMed  Google Scholar 

  48. Choi, J. C. Genetics of cerebral small vessel disease. J. Stroke 17, 7–16 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ikram, M. A. et al. Genetics of vascular dementia — review from the ICVD working group. BMC Med. 15, 48 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Tan, R., Traylor, M., Rutten-Jacobs, L. & Markus, H. New insights into mechanisms of small vessel disease stroke from genetics. Clin. Sci. 131, 515–531 (2017).

    Article  CAS  Google Scholar 

  51. Schneider, J. A., Wilson, R. S., Bienias, J. L., Evans, D. A. & Bennett, D. A. Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology. Neurology 62, 1148–1155 (2004).

    Article  CAS  PubMed  Google Scholar 

  52. Gold, G., Giannakopoulos, P., Herrmann, F. R., Bouras, C. & Kövari, E. Identification of Alzheimer and vascular lesion thresholds for mixed dementia. Brain 130, 2830–2836 (2007).

    Article  PubMed  Google Scholar 

  53. Skrobot, O. A. et al. Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment. Brain 139, 2957–2969 (2016).

    Article  PubMed  Google Scholar 

  54. Deramecourt, V. et al. Staging and natural history of cerebrovascular pathology in dementia. Neurology 78, 1043–1050 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Arvanitakis, Z. et al. The relationship of cerebral vessel pathology to brain microinfarcts. Brain Pathol. 27, 77–85 (2017).

    Article  CAS  PubMed  Google Scholar 

  56. Lin, W.-L., Castanedes-Casey, M. & Dickson, D. W. Transactivation response DNA-binding protein 43 microvasculopathy in frontotemporal degeneration and familial Lewy body disease. J. Neuropathol. Exp. Neurol. 68, 1167–1176 (2009).

    Article  CAS  PubMed  Google Scholar 

  57. Dudvarski Stankovic, N., Teodorczyk, M., Ploen, R., Zipp, F. & Schmidt, M. H. H. Microglia-blood vessel interactions: a double-edged sword in brain pathologies. Acta Neuropathol. 131, 347–363 (2016).

    Article  PubMed  Google Scholar 

  58. Longstreth, W. T. Brain abnormalities in the elderly: frequency and predictors in the United States (the Cardiovascular Health Study). Cardiovascular Health Study Collaborative Research Group. J. Neural Transm. Suppl. 53, 9–16 (1998).

    Article  PubMed  Google Scholar 

  59. Schneider, J. A. et al. Relation of cerebral infarctions to dementia and cognitive function in older persons. Neurology 60, 1082–1088 (2003).

    Article  CAS  PubMed  Google Scholar 

  60. Troncoso, J. C. et al. Effect of infarcts on dementia in the Baltimore longitudinal study of aging. Ann. Neurol. 64, 168–176 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Arvanitakis, Z., Leurgans, S. E., Barnes, L. L., Bennett, D. A. & Schneider, J. A. Microinfarct pathology, dementia, and cognitive systems. Stroke 42, 722–727 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  62. James, B. D., Bennett, D. A., Boyle, P. A., Leurgans, S. & Schneider, J. A. Dementia from Alzheimer disease and mixed pathologies in the oldest old. JAMA 307, 1798–1800 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Arvanitakis, Z., Capuano, A. W., Leurgans, S. E., Bennett, D. A. & Schneider, J. A. Relation of cerebral vessel disease to Alzheimer's disease dementia and cognitive function in elderly people: a cross-sectional study. Lancet Neurol. 15, 934–943 (2016). This is a detailed study of small and large vessel disease and their role as a mixed pathology with Alzheimer disease pathology that lowers the threshold for dementia even in the absence of infarcts.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Makin, S. D. J., Turpin, S., Dennis, M. S. & Wardlaw, J. M. Cognitive impairment after lacunar stroke: systematic review and meta-analysis of incidence, prevalence and comparison with other stroke subtypes. J. Neurol. Neurosurg. Psychiatry 84, 893–900 (2013).

    Article  PubMed  Google Scholar 

  65. Snowdon, D. A. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA 277, 813–817 (1997).

    Article  CAS  PubMed  Google Scholar 

  66. White, L. Brain lesions at autopsy in older Japanese-American men as related to cognitive impairment and dementia in the final years of life: a summary report from the Honolulu-Asia aging study. J. Alzheimers. Dis. 18, 713–725 (2009).

    Article  PubMed  Google Scholar 

  67. Sonnen, J. A. et al. Pathological correlates of dementia in a longitudinal, population-based sample of aging. Ann. Neurol. 62, 406–413 (2007).

    Article  PubMed  Google Scholar 

  68. 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 

  69. Westover, M. B., Bianchi, M. T., Yang, C., Schneider, J. A. & Greenberg, S. M. Estimating cerebral microinfarct burden from autopsy samples. Neurology 80, 1365–1369 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Smith, E. E. et al. Cerebral microinfarcts: the invisible lesions. Lancet Neurol. 11, 272–282 (2012). This is a comprehensive review of the importance of cerebral microinfarcts, which are related to VCI but are poorly recognized in clinical practice.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Okamoto, Y. et al. Cortical microinfarcts in Alzheimer's disease and subcortical vascular dementia. Neuroreport 20, 990–996 (2009).

    Article  PubMed  Google Scholar 

  72. van Veluw, S. J. et al. Microbleed and microinfarct detection in amyloid angiopathy: a high-resolution MRI-histopathology study. Brain 139, 3151–3162 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  73. van Veluw, S. J. et al. In vivo detection of cerebral cortical microinfarcts with high-resolution 7T MRI. J. Cereb. Blood Flow Metab. 33, 322–329 (2013).

    Article  PubMed  Google Scholar 

  74. van Veluw, S. J. et al. Cortical microinfarcts on 3T MRI: clinical correlates in memory-clinic patients. Alzheimers Dement. 11, 1500–1509 (2015).

    Article  PubMed  Google Scholar 

  75. Hilal, S. et al. Cortical cerebral microinfarcts on 3T MRI. Neurology 87, 1583–1590 (2016).

    Article  PubMed  Google Scholar 

  76. Doyle, K. P. et al. B-Lymphocyte-mediated delayed cognitive impairment following stroke. J. Neurosci. 35, 2133–2145 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Jin, W.-N. et al. Depletion of microglia exacerbates postischemic inflammation and brain injury. J. Cereb. Blood Flow Metab. 37, 2224–2236 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Rosenberg, G. A., Bjerke, M. & Wallin, A. Multimodal markers of inflammation in the subcortical ischemic vascular disease type of vascular cognitive impairment. Stroke 45, 1531–1538 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Carare, R. O., Hawkes, C. A., Jeffrey, M., Kalaria, R. N. & Weller, R. O. Review: Cerebral amyloid angiopathy, prion angiopathy, CADASIL and the spectrum of protein elimination failure angiopathies (PEFA) in neurodegenerative disease with a focus on therapy. Neuropathol. Appl. Neurobiol. 39, 593–611 (2013).

    Article  CAS  PubMed  Google Scholar 

  80. Wang, M. et al. Focal solute trapping and global glymphatic pathway impairment in a murine model of multiple microinfarcts. J. Neurosci. 37, 2870–2877 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Schrag, M. & Greer, D. M. Clinical associations of cerebral microbleeds on magnetic resonance neuroimaging. J. Stroke Cerebrovasc. Dis. 23, 2489–2497 (2014).

    Article  PubMed  Google Scholar 

  82. Benedictus, M. R. et al. Microbleeds, mortality, and stroke in Alzheimer disease. JAMA Neurol. 72, 539 (2015). This paper shows that cortical microbleeds are associated with an increased risk of stroke-related mortality.

    Article  PubMed  Google Scholar 

  83. Chung, C.-P. et al. Strictly lobar cerebral microbleeds are associated with cognitive impairment. Stroke 47, 2497–2502 (2016).

    Article  PubMed  Google Scholar 

  84. Hase, Y., Horsburgh, K., Ihara, M. & Kalaria, R. N. White matter degeneration in vascular and other ageing-related dementias. J. Neurochem. https://doi.org/10.1111/jnc.14271 (2017).

    Article  CAS  PubMed  Google Scholar 

  85. Wharton, S. B., Simpson, J. E., Brayne, C. & Ince, P. G. Age-associated white matter lesions: the MRC Cognitive Function and Ageing Study. Brain Pathol. 25, 35–43 (2015).

    Article  PubMed  Google Scholar 

  86. Joutel, A. & Chabriat, H. Pathogenesis of white matter changes in cerebral small vessel diseases: beyond vessel-intrinsic mechanisms. Clin. Sci. 131, 635–651 (2017).

    Article  Google Scholar 

  87. Boyle, P. A. et al. Cerebral amyloid angiopathy and cognitive outcomes in community-based older persons. Neurology 85, 1930–1936 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Yu, L. et al. APOE and cerebral amyloid angiopathy in community-dwelling older persons. Neurobiol. Aging 36, 2946–2953 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Hilal, S. et al. Subcortical atrophy in cognitive impairment and dementia. J. Alzheimer' Dis. 48, 813–823 (2015).

    Article  Google Scholar 

  90. Jagust, W. J. et al. Neuropathological basis of magnetic resonance images in aging and dementia. Ann. Neurol. 63, 72–80 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Erten-Lyons, D. et al. Neuropathologic basis of white matter hyperintensity accumulation with advanced age. Neurology 81, 977–983 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  92. Hinman, J. D., Lee, M. D., Tung, S., Vinters, H. V. & Carmichael, S. T. Molecular disorganization of axons adjacent to human lacunar infarcts. Brain 138, 736–745 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Saggu, R. et al. Astroglial NF-kB contributes to white matter damage and cognitive impairment in a mouse model of vascular dementia. Acta Neuropathol. Commun. 4, 76 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Udaka, F., Sawada, H. & Kameyama, M. White matter lesions and dementia: MRI-pathological correlation. Ann. NY Acad. Sci. 977, 411–415 (2002).

    Article  PubMed  Google Scholar 

  95. Chen, A. et al. Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia. Brain 139, 242–258 (2016).

    Article  PubMed  Google Scholar 

  96. Burton, E. et al. Hyperintensities and fronto-subcortical atrophy on MRI are substrates of mild cognitive deficits after stroke. Dement. Geriatr. Cogn. Disord. 16, 113–118 (2003).

    Article  PubMed  Google Scholar 

  97. Burrows, F. et al. Systemic inflammation affects reperfusion following transient cerebral ischaemia. Exp. Neurol. 277, 252–260 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Danton, G. H. & Dietrich, W. D. Inflammatory mechanisms after ischemia and stroke. J. Neuropathol. Exp. Neurol. 62, 127–136 (2003).

    Article  CAS  PubMed  Google Scholar 

  99. Adam, N., Kandelman, S., Mantz, J., Chrétien, F. & Sharshar, T. Sepsis-induced brain dysfunction. Expert Rev. Anti. Infect. Ther. 11, 211–221 (2013).

    Article  CAS  PubMed  Google Scholar 

  100. Sudduth, T. L., Powell, D. K., Smith, C. D., Greenstein, A. & Wilcock, D. M. Induction of hyperhomocysteinemia models vascular dementia by induction of cerebral microhemorrhages and neuroinflammation. J. Cereb. Blood Flow Metab. 33, 708–715 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Olichney, J. M. et al. Association between severe cerebral amyloid angiopathy and cerebrovascular lesions in Alzheimer disease is not a spurious one attributable to apolipoprotein E4. Arch. Neurol. 57, 869–874 (2000).

    Article  CAS  PubMed  Google Scholar 

  102. Bell, R. D. & Zlokovic, B. V. Neurovascular mechanisms and blood–brain barrier disorder in Alzheimer's disease. Acta Neuropathol. 118, 103–113 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Faraco, G. et al. Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension. J. Clin. Invest. 126, 4674–4689 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  104. Montagne, A. et al. Blood-brain barrier breakdown in the aging human hippocampus. Neuron 85, 296–302 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Bakker, E. N. T. P. et al. Lymphatic clearance of the brain: perivascular, paravascular and significance for neurodegenerative diseases. Cell. Mol. Neurobiol. 36, 181–194 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Tarantini, S., Tran, C. H. T., Gordon, G. R., Ungvari, Z. & Csiszar, A. Impaired neurovascular coupling in aging and Alzheimer's disease: contribution of astrocyte dysfunction and endothelial impairment to cognitive decline. Exp. Gerontol. 94, 52–58 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. Farkas, E. et al. Experimental cerebral hypoperfusion induces white matter injury and microglial activation in the rat brain. Acta Neuropathol. 108, 57–64 (2004).

    Article  PubMed  Google Scholar 

  108. Michaud, M. et al. Proinflammatory cytokines, aging, and age-related diseases. J. Am. Med. Dir. Assoc. 14, 877–882 (2013).

    Article  PubMed  Google Scholar 

  109. Ciolli, L. et al. The VAS-COG clinic: an out-patient service for patients with cognitive and behavioral consequences of cerebrovascular diseases. Neurol. Sci. 33, 1277–1283 (2012).

    Article  PubMed  Google Scholar 

  110. McKhann, G. et al. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34, 939–944 (1984).

    Article  CAS  PubMed  Google Scholar 

  111. Chui, H. C. et al. Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer's Disease Diagnostic and Treatment Centers. Neurology 42, 473 (1992).

    Article  CAS  PubMed  Google Scholar 

  112. World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders. Clinical descriptions and diagnostic guidelines (WHO, Geneva, 1992)

  113. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th edn (American Psychiatric Association, 1994).

  114. Pohjasvaara, T., Mantyla, R., Ylikoski, R., Kaste, M. & Erkinjuntti, T. Comparison of different clinical criteria (DSM-III, ADDTC, ICD-10, NINDS-AIREN, DSM-IV) for the diagnosis of vascular dementia. Stroke 31, 2952–2957 (2000).

    Article  CAS  PubMed  Google Scholar 

  115. Pantoni, L., Garcia, J. H. & Brown, G. G. Vascular pathology in three cases of progressive cognitive deterioration. J. Neurol. Sci. 135, 131–139 (1996).

    Article  CAS  PubMed  Google Scholar 

  116. Staekenborg, S. S. et al. Neurological signs in relation to type of cerebrovascular disease in vascular dementia. Stroke 39, 317–322 (2007).

    Article  PubMed  Google Scholar 

  117. Erkinjuntti, T. et al. in Advances in Dementia Research (eds Jellinger, K., Schmidt, R. & Windisch, M. ) 23–30 (Springer, 2000).

    Book  Google Scholar 

  118. Bastos-Leite, A. J. et al. The contribution of medial temporal lobe atrophy and vascular pathology to cognitive impairment in vascular dementia. Stroke 38, 3182–3185 (2007).

    Article  PubMed  Google Scholar 

  119. Staekenborg, S. S. et al. Behavioural and psychological symptoms in vascular dementia; differences between small- and large-vessel disease. J. Neurol. Neurosurg. Psychiatry 81, 547–551 (2009).

    Article  PubMed  Google Scholar 

  120. Hachinski, V. et al. National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke 37, 2220–2241 (2006).

    Article  PubMed  Google Scholar 

  121. Skrobot, O. A. et al. Progress toward standardized diagnosis of vascular cognitive impairment: guidelines from the Vascular Impairment of Cognition Classification Consensus Study. Alzheimers Dement. https://doi.org/10.1016/j.jalz.2017.09.007 (2017). This study describes protocols for the diagnosis of VCI based on the results of a Delphi consensus study, conducted in a large, multinational group of researchers, that aimed to achieve consensus on clinical diagnosis of VCI.

    Article  Google Scholar 

  122. METACOHORTS Consortium. METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: an initiative of the Joint Programme for Neurodegenerative Disease Research. Alzheimers Dement. 12, 1235–1249 (2016).

    Article  Google Scholar 

  123. Sachdev, P. S. et al. STROKOG (Stroke and Cognition Consortium): an international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease. Alzheimers Dement. 7, 11–23 (2017).

    Google Scholar 

  124. Wardlaw, J. M. et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 12, 822–838 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  125. Salvadori, E. et al. Development and psychometric properties of a neuropsychological battery for mild cognitive impairment with small vessel disease: the VMCI-Tuscany Study. J. Alzheimers. Dis. 43, 1313–1323 (2015).

    Article  PubMed  Google Scholar 

  126. Nasreddine, Z. S. et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J. Am. Geriatr. Soc. 53, 695–699 (2005).

    Article  PubMed  Google Scholar 

  127. Sorbi, S. et al. EFNS-ENS Guidelines on the diagnosis and management of disorders associated with dementia. Eur. J. Neurol. 19, 1159–1179 (2012).

    Article  CAS  PubMed  Google Scholar 

  128. Schoonenboom, N. S. M. et al. Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort. Neurology 78, 47–54 (2012).

    Article  CAS  PubMed  Google Scholar 

  129. Wallin, A. et al. Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease — a consensus report. BMC Neurol. 17, 102 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Kalaria, R. N. Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer's disease. Acta Neuropathol. 131, 659–685 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  131. Pantoni, L. et al. Postmortem examination of vascular lesions in cognitive impairment: a survey among neuropathological services. Stroke 37, 1005–1009 (2006).

    Article  PubMed  Google Scholar 

  132. Kalaria, R. N. & Ihara, M. Medial temporal lobe atrophy is the norm in cerebrovascular dementias. Eur. J. Neurol. 24, 539–540 (2017).

    Article  CAS  PubMed  Google Scholar 

  133. de Bruijn, R. F. A. G. et al. The potential for prevention of dementia across two decades: the prospective, population-based Rotterdam Study. BMC Med. 13, 132 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  134. Norton, S., Matthews, F. E., Barnes, D. E., Yaffe, K. & Brayne, C. Potential for primary prevention of Alzheimer's disease: an analysis of population-based data. Lancet Neurol. 13, 788–794 (2014).

    Article  PubMed  Google Scholar 

  135. Moll van Charante, E. P. et al. Effectiveness of a 6-year multidomain vascular care intervention to prevent dementia (preDIVA): a cluster-randomised controlled trial. Lancet 388, 797–805 (2016).

    Article  PubMed  Google Scholar 

  136. Dichgans, M. & Zietemann, V. Prevention of vascular cognitive impairment. Stroke 43, 3137–3146 (2012).

    Article  PubMed  Google Scholar 

  137. Ngandu, T. 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 385, 2255–2263 (2015).

    Article  PubMed  Google Scholar 

  138. Smith, E. E. et al. Prevention of stroke in patients with silent cerebrovascular disease: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 48, e44–e71 (2017). This paper summarizes the evidence on the diagnosis and management of silent cerebrovascular disease to prevent stroke and concludes that primary stroke prevention is indicated in patients with silent brain infarcts, WMHs or microbleeds.

    PubMed  Google Scholar 

  139. Kernan, W. N. et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke 45, 2160–2236 (2014).

    Article  PubMed  Google Scholar 

  140. Mok, V. C. T. et al. Early-onset and delayed-onset poststroke dementia — revisiting the mechanisms. Nat. Rev. Neurol. 13, 148–159 (2017).

    Article  PubMed  Google Scholar 

  141. Pendlebury, S. T. & Rothwell, P. M. Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis. Lancet Neurol. 8, 1006–1018 (2009).

    Article  PubMed  Google Scholar 

  142. 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 

  143. Diener, H.-C. 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. 7, 875–884 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Pearce, L. A. et al. Effects of long-term blood pressure lowering and dual antiplatelet treatment on cognitive function in patients with recent lacunar stroke: a secondary analysis from the SPS3 randomised trial. Lancet Neurol. 13, 1177–1185 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Mok, V. C. T. et al. Delayed-onset dementia after stroke or transient ischemic attack. Alzheimers Dement. 12, 1167–1176 (2016).

    Article  PubMed  Google Scholar 

  146. Douiri, A., McKevitt, C., Emmett, E. S., Rudd, A. G. & Wolfe, C. D. A. Long-term effects of secondary prevention on cognitive function in stroke patients. Circulation 128, 1341–1348 (2013).

    Article  PubMed  Google Scholar 

  147. The SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N. Engl. J. Med. 373, 2103–2116 (2015).

    Article  PubMed Central  CAS  Google Scholar 

  148. [No authors listed.] Systolic Blood Pressure Intervention Trial (SPRINT) Overview. National Heart, Lung and Blood Institutehttps://www.nhlbi.nih.gov/news/systolic-blood-pressure-intervention-trial-sprint-overview (2017).

  149. Birns, J. & Kalra, L. Cognitive function and hypertension. J. Hum. Hypertens. 23, 86–96 (2008).

    Article  PubMed  Google Scholar 

  150. Thoonsen, H. et al. Aspirin in Alzheimer's disease: increased risk of intracerebral hemorrhage: cause for concern? Stroke 41, 2690–2692 (2010).

    Article  CAS  PubMed  Google Scholar 

  151. Van der Flier, W. M. & Cordonnier, C. Microbleeds in vascular dementia: clinical aspects. Exp. Gerontol. 47, 853–857 (2012).

    Article  PubMed  Google Scholar 

  152. Cordonnier, C. & van der Flier, W. M. Brain microbleeds and Alzheimer's disease: innocent observation or key player? Brain 134, 335–344 (2011).

    Article  PubMed  Google Scholar 

  153. Wang, Z., Soo, Y. O. Y. & Mok, V. C. T. Cerebral microbleeds. Stroke 45, 2811–2817 (2014).

    Article  PubMed  Google Scholar 

  154. Jacobs, V. et al. Long-term population-based cerebral ischemic event and cognitive outcomes of direct oral anticoagulants compared with warfarin among long-term anticoagulated patients for atrial fibrillation. Am. J. Cardiol. 118, 210–214 (2016).

    Article  PubMed  Google Scholar 

  155. Matz, K. et al. Multidomain lifestyle interventions for the prevention of cognitive decline after ischemic stroke. Stroke 46, 2874–2880 (2015).

    Article  PubMed  Google Scholar 

  156. Benjamin, P. et al. Progression of MRI markers in cerebral small vessel disease: sample size considerations for clinical trials. J. Cereb. Blood Flow Metab. 36, 228–240 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  157. Schmidt, R. et al. White matter lesion progression in LADIS: frequency, clinical effects, and sample size calculations. Stroke 43, 2643–2647 (2012).

    Article  PubMed  Google Scholar 

  158. Prins, N. D. & Scheltens, P. White matter hyperintensities, cognitive impairment and dementia: an update. Nat. Rev. Neurol. 11, 157–165 (2015).

    Article  PubMed  Google Scholar 

  159. Inzitari, D. et al. Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort. BMJ 339, b2477 (2009). This study shows the independent contribution of WMHs detected by MRI to loss of independence and risk of mortality.

    Article  PubMed  PubMed Central  Google Scholar 

  160. Gouw, A. A. et al. On the etiology of incident brain lacunes: longitudinal observations from the lADIS study. Stroke 39, 3083–3085 (2008).

    Article  PubMed  Google Scholar 

  161. Gouw, A. A. et al. Progression of white matter hyperintensities and incidence of new lacunes over a 3-year period: the Leukoaraiosis and Disability study. Stroke 39, 1414–1420 (2008).

    Article  PubMed  Google Scholar 

  162. Dufouil, C. Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging substudy. Circulation 112, 1644–1650 (2005).

    Article  PubMed  Google Scholar 

  163. Hasegawa, Y. et al. Effects of perindopril-based blood pressure lowering and of patient characteristics on the progression of silent brain infarct: the Perindopril Protection against Recurrent Stroke Study (PROGRESS) CT substudy in Japan. Hypertens. Res. 27, 147–156 (2004).

    Article  CAS  PubMed  Google Scholar 

  164. van Dijk, E. J. et al. Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan study. Stroke 39, 2712–2719 (2008).

    Article  PubMed  Google Scholar 

  165. Mok, V. C. T. et al. Effects of statins on the progression of cerebral white matter lesion. J. Neurol. 256, 750–757 (2009).

    Article  CAS  PubMed  Google Scholar 

  166. Fu, J. H. et al. Effects of statins on progression of subclinical brain infarct. Cerebrovasc. Dis. 30, 51–56 (2010).

    Article  CAS  PubMed  Google Scholar 

  167. Xiong, Y. et al. Prestroke statins, progression of white matter hyperintensities, and cognitive decline in stroke patients with confluent white matter hyperintensities. Neurotherapeutics 11, 606–611 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  168. ten Dam, V. H. et al. Effect of pravastatin on cerebral infarcts and white matter lesions. Neurology 64, 1807–1809 (2005).

    Article  CAS  PubMed  Google Scholar 

  169. Cavalieri, M. et al. B vitamins and magnetic resonance imaging-detected ischemic brain lesions in patients with recent transient ischemic attack or stroke: The VITAmins TO Prevent Stroke (VITATOPS) MRI-substudy. Stroke 43, 3266–3270 (2012).

    Article  CAS  PubMed  Google Scholar 

  170. VITATOPS Trial Study Group. B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. Lancet Neurol. 9, 855–865 (2010).

    Article  CAS  Google Scholar 

  171. Gopalan, Y. et al. Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter. Stroke 45, 1422–1428 (2014).

    Article  CAS  PubMed  Google Scholar 

  172. Richard, E., Gouw, A. A., Scheltens, P. & van Gool, W. A. Vascular care in patients with alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the Evaluation of Vascular Care in Alzheimer's Disease (EVA) Study. Stroke 41, 554–556 (2010).

    Article  PubMed  Google Scholar 

  173. Leeuwis, A. E. et al. Design of the ExCersion-VCI study: the effect of aerobic exercise on cerebral perfusion in patients with vascular cognitive impairment. Alzheimers Dement. 3, 157–165 (2017).

    Article  Google Scholar 

  174. Cyarto, E. V. et al. Protocol for a randomized controlled trial evaluating the effect of physical activity on delaying the progression of white matter changes on MRI in older adults with memory complaints and mild cognitive impairment: the AIBL Active trial. BMC Psychiatry 12, 167 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  175. Baykara, E. et al. A novel imaging marker for small vessel disease based on skeletonization of white matter tracts and diffusion histograms. Ann. Neurol. 80, 581–592 (2016).

    Article  PubMed  Google Scholar 

  176. Yang, J. et al. Risk factors for incident dementia after stroke and transient ischemic attack. Alzheimers Dement. 11, 16–23 (2015).

    Article  PubMed  Google Scholar 

  177. Lee, J. H. et al. Identification of pure subcortical vascular dementia using 11C-Pittsburgh compound B. Neurology 77, 18–25 (2011).

    Article  CAS  PubMed  Google Scholar 

  178. Liu, W. et al. Influence of amyloid-β on cognitive decline after stroke/transient ischemic attack. Stroke 46, 3074–3080 (2015).

    Article  CAS  PubMed  Google Scholar 

  179. Scheltens, P. et al. Alzheimer's disease. Lancet 388, 505–517 (2016).

    Article  CAS  PubMed  Google Scholar 

  180. Sevigny, J. et al. The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. Nature 537, 50–56 (2016).

    Article  CAS  PubMed  Google Scholar 

  181. Kavirajan, H. & Schneider, L. S. Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials. Lancet Neurol. 6, 782–792 (2007).

    Article  CAS  PubMed  Google Scholar 

  182. Roman, G. C. et al. Randomized, placebo-controlled, clinical trial of donepezil in vascular dementia: differential effects by hippocampal size. Stroke 41, 1213–1221 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Mbius, H. J. & Stffler, A. Memantine in vascular dementia. Int. Psychogeriatr. 15, 207–213 (2003).

    Article  Google Scholar 

  184. Guekht, A., Skoog, I., Edmundson, S., Zakharov, V. & Korczyn, A. D. ARTEMIDA Trial (a randomized trial of efficacy, 12 months international double-blind actovegin). Stroke 48, 1262–1270 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Chen, N. et al. Cerebrolysin for vascular dementia. Cochrane Database Syst. Rev. 1, CD008900 (2013)

    Google Scholar 

  186. Pantoni, L. et al. Efficacy and safety of nimodipine in subcortical vascular dementia: a randomized placebo-controlled trial. Stroke 36, 619–624 (2005).

    Article  CAS  PubMed  Google Scholar 

  187. Jia, J. et al. The effects of DL-3-n-butylphthalide in patients with vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease: a multicentre, randomized, double-blind, placebo-controlled trial. Alzheimers Dement. 12, 89–99 (2016).

    Article  PubMed  Google Scholar 

  188. Napryeyenko, O., Sonnik, G. & Tartakovsky, I. Efficacy and tolerability of Ginkgo biloba extract EGb 761 by type of dementia: analyses of a randomised controlled trial. J. Neurol. Sci. 283, 224–229 (2009).

    Article  CAS  PubMed  Google Scholar 

  189. Ihl, R., Tribanek, M., Bachinskaya, N. & GOTADAY Study Group. Efficacy and tolerability of a once daily formulation of Ginkgo biloba extract EGb 761® in Alzheimer's disease and vascular dementia: results from a randomised controlled trial. Pharmacopsychiatry 45, 41–46 (2012).

    Article  CAS  PubMed  Google Scholar 

  190. Yuan, Q., Wang, C., Shi, J. & Lin, Z. Effects of Ginkgo biloba on dementia: an overview of systematic reviews. J. Ethnopharmacol. 195, 1–9 (2017).

    Article  CAS  PubMed  Google Scholar 

  191. Tang, Y. et al. The efficacy of Cognitive training in patients with VAsCular Cognitive Impairment, No dEmentia (the Cog-VACCINE study): study protocol for a randomized controlled trial. Trials 17, 392 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  192. Guerra, A. et al. Transcranial magnetic stimulation studies in Alzheimer's disease. Int. J. Alzheimers. Dis. 2011, 1–9 (2011).

    Article  Google Scholar 

  193. Kubis, N. Non-invasive brain stimulation to enhance post-stroke recovery. Front. Neural Circuits 10, 56 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  194. Baker, E. W. et al. Induced pluripotent stem cell-derived neural stem cell therapy enhances recovery in an ischemic stroke pig model. Sci. Rep. 7, 10075 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  195. Bang, O. Y., Kim, E. H., Cha, J. M. & Moon, G. J. Adult stem cell therapy for stroke: challenges and progress. J. Stroke 18, 256–266 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  196. de Hert, M., Schreurs, V., Vancampfort, D. & van Winkel, R. Metabolic syndrome in people with schizophrenia: a review. World Psychiatry 8, 15–22 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  197. Wang, P. S. et al. Risk of death in elderly users of conventional versus atypical antipsychotic medications. N. Engl. J. Med. 353, 2335–2341 (2005).

    Article  CAS  PubMed  Google Scholar 

  198. Anderson, I. M. & Tomenson, B. M. Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a meta-analysis. BMJ 310, 1433–1438 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Bondon-Guitton, E. et al. Drug-induced parkinsonism: a review of 17 years’ experience in a regional pharmacovigilance center in France. Mov. Disord. 26, 2226–2231 (2011).

    Article  PubMed  Google Scholar 

  200. Korczyn, A. D. Vascular parkinsonism — characteristics, pathogenesis and treatment. Nat. Rev. Neurol. 11, 319–326 (2015).

    Article  PubMed  Google Scholar 

  201. [No authors listed.] The World Health Organization Quality of Life assessment (WHOQOL): position paper from the World Health Organization. Soc. Sci. Med. 41, 1403–1409 (1995).

  202. Bowling, A. et al. Quality of life in dementia: a systematically conducted narrative review of dementia-specific measurement scales. Aging Ment. Health 19, 13–31 (2014). This is a recent and comprehensive review of QOL scales for dementia.

    Article  PubMed  Google Scholar 

  203. Logsdon, R. G., Gibbons, L. E., McCurry, S. M. & Teri, L. Assessing quality of life in older adults with cognitive impairment. Psychosom. Med. 64, 510–519 (2002).

    Article  PubMed  Google Scholar 

  204. Brod, M., Stewart, A. L., Sands, L. & Walton, P. Conceptualization and measurement of quality of life in dementia: the Dementia Quality of Life Instrument (DQoL). Gerontologist 39, 25–36 (1999).

    Article  CAS  PubMed  Google Scholar 

  205. Weiner, M. F. et al. The quality of life in late-stage dementia (QUALID) scale. J. Am. Med. Dir. Assoc. 1, 114–116 (2000).

    CAS  PubMed  Google Scholar 

  206. Ettema, T. P., Dröes, R.-M., de Lange, J., Mellenbergh, G. J. & Ribbe, M. W. QUALIDEM: development and evaluation of a dementia specific quality of life instrument — validation. Int. J. Geriatr. Psychiatry 22, 424–430 (2007).

    Article  PubMed  Google Scholar 

  207. Williams, L. S., Weinberger, M., Harris, L. E., Clark, D. O. & Biller, J. Development of a stroke-specific quality of life scale. Stroke 30, 1362–1369 (1999).

    Article  CAS  PubMed  Google Scholar 

  208. Lawton, M. P. Quality of life in Alzheimer disease. Alzheimer Dis. Assoc. Disord. 8, 138–150 (1994).

    Article  PubMed  Google Scholar 

  209. Etters, L., Goodall, D. & Harrison, B. E. Caregiver burden among dementia patient caregivers: a review of the literature. J. Am. Acad. Nurse Pract. 20, 423–428 (2008).

    Article  PubMed  Google Scholar 

  210. Thomas, P. et al. Dementia patients caregivers quality of life: the PIXEL study. Int. J. Geriatr. Psychiatry 21, 50–56 (2006).

    Article  PubMed  Google Scholar 

  211. Belle, S. H. et al. Enhancing the quality of life of dementia caregivers from different ethnic or racial groups: a randomized, controlled trial. Ann. Intern. Med. 145, 727–738 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  212. Graff, M. J. L. et al. Effects of community occupational therapy on quality of life, mood, and health status in dementia patients and their caregivers: a randomized controlled trial. Journals Gerontol. Ser. A 62, 1002–1009 (2007).

    Article  Google Scholar 

  213. van der Flier, W. M. et al. Interaction of medial temporal lobe atrophy and white matter hyperintensities in AD. Neurology 62, 1862–1864 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  215. Beach, T. G. et al. Circle of Willis atherosclerosis: association with Alzheimer's disease, neuritic plaques and neurofibrillary tangles. Acta Neuropathol. 113, 13–21 (2006).

    Article  PubMed  Google Scholar 

  216. Barnes, J. et al. Vascular and Alzheimer's disease markers independently predict brain atrophy rate in Alzheimer's Disease Neuroimaging Initiative controls. Neurobiol. Aging 34, 1996–2002 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Goos, J. D. C. et al. Patients with Alzheimer disease with multiple microbleeds. Stroke 40, 3455–3460 (2009).

    Article  PubMed  Google Scholar 

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Contributions

Introduction (W.M.v.d.F.); Epidemiology (I.S.); Mechanisms/pathophysiology (J.A.S.); Diagnosis, screening and prevention (L.P. and P.S.); Management (V.M.); Quality of life (C.L.H.C.); Outlook (All); Overview of Primer (W.M.v.d.F. and P.S.).

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Correspondence to Wiesje M. van der Flier.

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Competing interests

W.M.v.d.F. has been an invited speaker at Boehringer Ingelheim and has received grant support from Boehringer Ingelheim, Biogen MA Inc, Piramal Neuroimaging, Roche BV, Janssen Stellar and Combinostics. All funding is paid to her institution. I.S. has been a consultant for Takeda and has given paid lectures for Takeda in relation to vascular dementia. J.A.S. has been on the scientific advisory boards of Genentech, Eli Lilly and Grifols and has received consultancy fees from Navidea Biopharmaceuticals and the Michael J. Fox Foundation. C.L.H.C. has received research support from Moleac, Nutricia, Lundbeck, Eisai, GlaxoSmithKline and Merck. All funding is paid to his institution. P.S. has acquired grant support from GE Healthcare, Danone Research, Piramal and Merck and, in the past 2 years, has received consultancy and speaker fees from GE Healthcare, Novartis, Nutricia, Probiodrug, Biogen, Lundbeck, Roche and EIP Pharma. All funding is paid to his institution. All other authors declare no competing interests.

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van der Flier, W., Skoog, I., Schneider, J. et al. Vascular cognitive impairment. Nat Rev Dis Primers 4, 18003 (2018). https://doi.org/10.1038/nrdp.2018.3

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