Skip to main content
SpringerLink
Log in

Pathophysiology of Vascular Cognitive Impairment (I): Theoretical Background

  • Chapter
  • First Online:
Book cover Stroke Revisited: Vascular Cognitive Impairment

Part of the book series: Stroke Revisited ((STROREV))

Abstract

Vascular cognitive impairment (VCI) describes a spectrum of cognitive changes occurring secondary to damage of the large and small vessels that supply blood to the brain. VCI has been recognized as the second most common cause of dementia and as the most common pathological comorbidity of Alzheimer’s disease. The pathogenesis of VCI appears to be heterogeneous, involving neurodegenerative mechanisms that remain to be fully understood. Stroke and vascular risk factors interfere with many processes subserved by the cerebral vasculature, maintaining cerebral homeostasis (for instance, maintaining and augmenting blood flow, oxygen, glucose supply), providing a structural and chemical barrier between the peripheral circulation and the brain parenchyma, serving intricate immunological functions, and providing a neurogenic niche for brain tissue repair. This chapter discusses the known and theoretical pathophysiological background of VCI, focusing on stroke and disruption of the neurovascular unit (NVU), which contribute to defects in neurotransmitter systems and to disruption of large-scale functionally co-activating networks, which contributes to cognitive deficits and decline.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80(4):844–66.

    Article  CAS  PubMed  Google Scholar 

  2. Armulik A, Genové G, Mäe M, et al. Pericytes regulate the blood–brain barrier. Nature. 2010;468(7323):557–61.

    Article  CAS  PubMed  Google Scholar 

  3. Ramirez J, Berezuk C, McNeely AA, et al. Imaging the perivascular space as a potential biomarker of neurovascular and neurodegenerative diseases. Cell Mol Neurobiol. 2016;36(2):289–99.

    Article  CAS  PubMed  Google Scholar 

  4. Chung C-P, Chou K-H, Chen W-T, et al. Strictly lobar cerebral microbleeds are associated with cognitive impairment. Stroke. 2016;47(10):2497–502.

    Article  PubMed  Google Scholar 

  5. Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci. 2011;12(12):723–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Marnane M, Al-Jawadi OO, Mortazavi S, et al. Periventricular hyperintensities are associated with elevated cerebral amyloid. Neurology. 2016;86(6):535–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Makedonov I, Black SE, MacIntosh BJ. Cerebral small vessel disease in aging and Alzheimer’s disease: a comparative study using MRI and SPECT. Eur J Neurol. 2013;20(2):243–50.

    Article  CAS  PubMed  Google Scholar 

  8. MacIntosh BJ, Swardfager W, Robertson AD, et al. Regional cerebral arterial transit time hemodynamics correlate with vascular risk factors and cognitive function in men with coronary artery disease. Am J Neuroradiol. 2015;36(2):295–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Keith J, Gao FQ, Noor R, et al. Collagenosis of the deep medullary veins: an underrecognized pathologic correlate of white matter hyperintensities and periventricular infarction? J Neuropathol Exp Neurol. 2017;76(4):299–312.

    Article  CAS  PubMed  Google Scholar 

  10. Kisler K, Nelson AR, Montagne A, et al. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat Rev Neurosci. 2017;18(7):419–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kisler K, Nelson AR, Rege SV, et al. Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain. Nat Neurosci. 2017;20(3):406–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yemisci M, Gursoy-Ozdemir Y, Vural A, et al. Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med. 2009;15(9):1031–7.

    Article  CAS  PubMed  Google Scholar 

  13. Swardfager W, Yu D, Scola G, et al. Peripheral lipid oxidative stress markers are related to vascular risk factors and subcortical small vessel disease. Neurobiol Aging. 2017;59:91–7.

    Article  CAS  PubMed  Google Scholar 

  14. van Exel E, de Craen AJM, Remarque EJ, et al. Interaction of atherosclerosis and inflammation in elderly subjects with poor cognitive function. Neurology. 2003;61(12):1695–701.

    Article  PubMed  Google Scholar 

  15. Toth P, Tucsek Z, Tarantini S, et al. IGF-1 deficiency impairs cerebral myogenic autoregulation in hypertensive mice. J Cereb Blood Flow Metab. 2014;34(12):1887–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rosenberg GA. Extracellular matrix inflammation in vascular cognitive impairment and dementia. Clin Sci. 2017;131(6):425–37.

    Article  CAS  Google Scholar 

  17. Iadecola C, Anrather J. The immunology of stroke: from mechanisms to translation. Nat Med. 2011;17(7):796–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Saggu R, Schumacher T, Gerich F, et al. Astroglial NF-kB contributes to white matter damage and cognitive impairment in a mouse model of vascular dementia. Acta Neuropathol Commun. 2016;4(1):76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Cai M, Lee JH, Yang EJ. Bee venom ameliorates cognitive dysfunction caused by neuroinflammation in an animal model of vascular dementia. Mol Neurobiol. 2017;54(8):5952–60.

    Article  CAS  PubMed  Google Scholar 

  20. Swardfager W, Winer DA, Herrmann N, et al. Interleukin-17 in post-stroke neurodegeneration. Neurosci Biobehav Rev. 2013;37(3):436–47.

    Article  CAS  PubMed  Google Scholar 

  21. Kim J-Y, Kim N, Yenari MA. Mechanisms and potential therapeutic applications of microglial activation after brain injury. CNS Neurosci Ther. 2015;21(4):309–19.

    Article  PubMed  Google Scholar 

  22. Choi SS, Lee HJ, Lim I, et al. Human astrocytes: secretome profiles of cytokines and chemokines. PLoS One. 2014;9(4):e92325.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Jellinger KA. Pathology and pathogenesis of vascular cognitive impairment: a critical update. Front Aging Neurosci. 2013;5:17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Muir RT, Lam B, Honjo K, et al. Trail making test elucidates neural substrates of specific poststroke executive dysfunctions. Stroke. 2015;46(10):2755–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Liu Q, Zhu Z, Teipel SJ, et al. White matter damage in the cholinergic system contributes to cognitive impairment in subcortical vascular cognitive impairment, no dementia. Front Aging Neurosci. 2017;9:47.

    PubMed  PubMed Central  Google Scholar 

  26. Gao F, Pettersen JA, Bocti C, et al. Is encroachment of the carotid termination into the substantia innominata associated with its atrophy and cognition in Alzheimer’s disease? Neurobiol Aging. 2013;34(7):1807–14.

    Article  PubMed  Google Scholar 

  27. Kalaria RN. Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer’s disease. Acta Neuropathol. 2016;131(5):659–85.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Black S, Roman GC, Geldmacher DS, et al. Efficacy and tolerability of donepezil in vascular dementia: positive results of a 24-week, multicenter, international, randomized, placebo-controlled clinical trial. Stroke. 2003;34(10):2323–30.

    Article  CAS  PubMed  Google Scholar 

  29. Lim J-S, Kim N, Jang MU, et al. Cortical hubs and subcortical cholinergic pathways as neural substrates of poststroke dementia. Stroke. 2014;45(4):1069–76.

    Article  PubMed  Google Scholar 

  30. McNeely AA, Ramirez J, Nestor SM, et al. Cholinergic subcortical hyperintensities in Alzheimer’s disease patients from the Sunnybrook Dementia Study: relationships with cognitive dysfunction and hippocampal atrophy. J Alzheimers Dis. 2015;43(3):785–96.

    Article  PubMed  Google Scholar 

  31. Lanctôt KL, O’Regan J, Schwartz Y, et al. Assessing cognitive effects of anticholinergic medications in patients with coronary artery disease. Psychosomatics. 2014;55(1):61–8.

    Article  PubMed  Google Scholar 

  32. Kirvell SL, Elliott MS, Kalaria RN, et al. Vesicular glutamate transporter and cognition in stroke: a case-control autopsy study. Neurology. 2010;75(20):1803–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Mijajlović MD, Pavlović A, Brainin M, et al. Post-stroke dementia—a comprehensive review. BMC Med. 2017;15(1):11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Gold AB, Herrmann N, Swardfager W, et al. The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment. J Neuroinflammation. 2011;8(1):17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Rezvani AH. Involvement of the NMDA system in learning and memory. In: Levin ED, Buccafusco JJ, editors. Animal models of cognitive impairment. Boca Raton, FL: CRC Press/Taylor & Francis; 2006.

    Google Scholar 

  36. Palomar FJ, Suarez A, Franco E, et al. Abnormal sensorimotor plasticity in CADASIL correlates with neuropsychological impairment. J Neurol Neurosurg Psychiatry. 2013;84(3):329–36.

    Article  PubMed  Google Scholar 

  37. Wang L, Zang Y, He Y, et al. Changes in hippocampal connectivity in the early stages of Alzheimer’s disease: evidence from resting state fMRI. NeuroImage. 2006;31(2):496–504.

    Article  PubMed  Google Scholar 

  38. Sun Y, Qin L, Zhou Y, et al. Abnormal functional connectivity in patients with vascular cognitive impairment, no dementia: a resting-state functional magnetic resonance imaging study. Behav Brain Res. 2011;223(2):388–94.

    Article  PubMed  Google Scholar 

  39. Yi L, Wang J, Jia L, et al. Structural and functional changes in subcortical vascular mild cognitive impairment: a combined voxel-based morphometry and resting-state fMRI study. PLoS One. 2012;7(9):e44758.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Broyd SJ, Demanuele C, Debener S, et al. Default-mode brain dysfunction in mental disorders: a systematic review. Neurosci Biobehav Rev. 2009;33(3):279–96.

    Article  PubMed  Google Scholar 

  41. Fernández PJ, Campoy G, García Santos JM, et al. Is there a specific pattern of attention deficit in mild cognitive impairment with subcortical vascular features? Evidence from the attention network test. Dement Geriatr Cogn Disord. 2011;31(4):268–75.

    Article  PubMed  Google Scholar 

  42. Silbert LC, Nelson C, Howieson DB, et al. Impact of white matter hyperintensity volume progression on rate of cognitive and motor decline. Neurology. 2008;71(2):108–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Biesbroek JM, Weaver NA, Hilal S, et al. Impact of strategically located white matter hyperintensities on cognition in memory clinic patients with small vessel disease. PLoS One. 2016;11(11):e0166261.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Ishikawa H, Meguro K, Ishii H, et al. Silent infarction or white matter hyperintensity and impaired attention task scores in a nondemented population: the Osaki-Tajiri project. J Stroke Cerebrovasc Dis. 2012;21(4):275–82.

    Article  PubMed  Google Scholar 

  45. Santiago C, Herrmann N, Swardfager W, et al. White matter microstructural integrity is associated with executive function and processing speed in older adults with coronary artery disease. Am J Geriatr Psychiatry. 2015;23(7):754–63.

    Article  PubMed  Google Scholar 

  46. Teipel SJ, Bokde ALW, Meindl T, et al. White matter microstructure underlying default mode network connectivity in the human brain. NeuroImage. 2010;49(3):2021–32.

    Article  PubMed  Google Scholar 

  47. Tuladhar AM, Reid AT, Shumskaya E, et al. Relationship between white matter hyperintensities, cortical thickness, and cognition. Stroke. 2015;46(2):425–32.

    Article  PubMed  Google Scholar 

  48. Nestor SM, Mišić B, Ramirez J, et al. Small vessel disease is linked to disrupted structural network covariance in Alzheimer’s disease. Alzheimers Dement. 2017;13(7):749–60.

    Article  PubMed  Google Scholar 

  49. Swardfager W, Cogo-Moreira H, Masellis M, et al. The effect of white matter hyperintensities on verbal memory; mediation by temporal lobe atrophy. Neurology. 2018;90(8):e673–82.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We would like to gratefully acknowledge the support from our colleagues, Sabrina Adamo and Fuqiang Gao from Sunnybrook Research Institute, for their contribution to the processing and labeling of the MR images. W.S. gratefully acknowledges support from the Alzheimer’s Association (US), Brain Canada, The Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre Department of Psychiatry, Sunnybrook Research Institute Hurvitz Brain Sciences Program, and the University of Toronto Department of Pharmacology and Toxicology. S.E.B. gratefully acknowledges financial and salary support from the Fondation Leducq, Canadian Institutes of Health Research (#125740 & #13129), Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Hurvitz Brain Sciences Research Program at Sunnybrook Research Institute, and the Linda C. Campbell Foundation. S.E.B. would also like to thank the Sunnybrook Research Institute, Sunnybrook Health Sciences Centre Department of Medicine, and the Brill Chair Neurology, University of Toronto, for financial and salary support.

Author information

Authors and Affiliations

  1. Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada

    Di Yu, Walter Swardfager & Sandra E. Black

  2. Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada

    Di Yu & Walter Swardfager

  3. Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, ON, Canada

    Di Yu, Walter Swardfager & Sandra E. Black

  4. LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, ON, Canada

    Di Yu, Walter Swardfager & Sandra E. Black

  5. University Health Network Toronto Rehabilitation Institute, Toronto, ON, Canada

    Walter Swardfager & Sandra E. Black

  6. Neurology Division, Department of Medicine, University of Toronto, Toronto, ON, Canada

    Sandra E. Black

Authors
  1. Di Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Walter Swardfager
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sandra E. Black
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Di Yu .

Editor information

Editors and Affiliations

  1. Department of Neurology, Seoul National University Hospital, Seoul, Korea (Republic of)

    Seung-Hoon Lee

  2. Department of Neurology, Hallym University Sacred Heart Hospital, Hallym Neurological Institute Hallym University College of Medicine, Anyang-si, Gyeonggi-do, Korea (Republic of)

    Jae-Sung Lim

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Science+Business Media Singapore

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Yu, D., Swardfager, W., Black, S.E. (2020). Pathophysiology of Vascular Cognitive Impairment (I): Theoretical Background. In: Lee, SH., Lim, JS. (eds) Stroke Revisited: Vascular Cognitive Impairment. Stroke Revisited. Springer, Singapore. https://doi.org/10.1007/978-981-10-1433-8_7

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-1433-8_7

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-1432-1

  • Online ISBN: 978-981-10-1433-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation