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Am J Physiol Heart Circ Physiol. 2017 Jan 1;312(1):H1-H20. doi: 10.1152/ajpheart.00581.2016. Epub 2016 Oct 28.

Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging.

Author information

1
Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
2
Department of Neurosurgery and Szentagothai Research Center, University of Pecs, Pecs, Hungary; and.
3
Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary.
4
Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; zoltan-ungvari@ouhsc.edu.

Abstract

Increasing evidence from epidemiological, clinical and experimental studies indicate that age-related cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including Alzheimer's disease. Understanding and targeting the age-related pathophysiological mechanisms that underlie vascular contributions to cognitive impairment and dementia (VCID) are expected to have a major role in preserving brain health in older individuals. Maintenance of cerebral perfusion, protecting the microcirculation from high pressure-induced damage and moment-to-moment adjustment of regional oxygen and nutrient supply to changes in demand are prerequisites for the prevention of cerebral ischemia and neuronal dysfunction. This overview discusses age-related alterations in three main regulatory paradigms involved in the regulation of cerebral blood flow (CBF): cerebral autoregulation/myogenic constriction, endothelium-dependent vasomotor function, and neurovascular coupling responses responsible for functional hyperemia. The pathophysiological consequences of cerebral microvascular dysregulation in aging are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages, microvascular rarefaction, and ischemic neuronal dysfunction and damage. Due to the widespread attention that VCID has captured in recent years, the evidence for the causal role of cerebral microvascular dysregulation in cognitive decline is critically examined.

KEYWORDS:

Alzheimer’s disease; blood-brain barrier; cerebral circulation; cerebrovascular; functional hyperemia; geroscience; microcirculation; myogenic constriction; neurovascular coupling; senescence; stroke; vascular aging

PMID:
27793855
PMCID:
PMC5283909
DOI:
10.1152/ajpheart.00581.2016
[Indexed for MEDLINE]
Free PMC Article

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