DOI: 10.1002/alz.081534 ISSN: 1552-5260

Cerebral blood flow dysregulation in dementia, Alzheimer’s disease and COVID19

Costantino Iadecola
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Cerebral blood vessels are essential for optimal brain health by maintaining the metabolic, thermal, biochemical and cellular homeostasis of the brain’s internal milieu. Alterations of the neurovasculature disrupt such vital homeostatic functions and are a frequent correlate of cognitive impairment in a wide variety of neurovascular, neurodegenerative, and neuroinflammatory pathologies.


Neurovascular pathologies (e.g., vascular cognitive impairment), neurodegenerative conditions (e.g., Alzheimer’s disease), and systemic infections associated with immune hyperactivation (e.g., COVID19), result in neurovascular dysfunction which may contribute to short‐ and long‐term impairment of cognition. The mechanisms by which neurovascular dysfunction lead to cognitive impairment are diverse and include: (a) alterations in the factors regulating the delivery of blood to the brain (coupling between neural activity and blood flow, autoregulation, endothelial vasoactivity), (b) alterations of the blood‐brain barrier, (c) vascular trophic factor deficiency resulting in increased vulnerability of neurons and glia to injury, (d) dysregulation of the brain’s immune surveillance, (e) reduced waste disposal through perivascular, paravascular (glymphatics), and transvascular clearance pathways. In addition, in COVID19 hypoxia and endothelial inflammation caused by cytokines and hemostatic abnormalities lead to endothelial dysfunction, microvascular occlusions, and increased the risk of stroke and hypoxic brain injury. Longer term consequences (long COVID) are likely to be linked to non‐resolving inflammation driven by persistence of the virus spike protein in the skull bone marrow, meninges, and brain.


Neurovascular alterations play a central role in the mechanisms of neurovascular, neurodegenerative and neuroimmune diseases resulting in cognitive impairment. Neurovascular dysfunction impairs cognition by promoting white matter damage, accumulation of pathogenic proteins (Abeta, tau, etc.) and neuroinflammation, and by reducing the resilience of the brain to injury. Interventions to improve neurovascular function may be beneficial in the management of these devastating conditions and should be considered as an added preventative or therapeutic approach.

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