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Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging
Open accessAbstract
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.
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“In addition, microvascular endothelial aging also disrupts the blood-brain barrier, which promotes neuroinflammation, exacerbating cognitive decline”
From Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain (2020) · cites this paper as Toth et al. 2017
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Self-citation
Metadata
- Authors
- Toth, P., Tarantini, S., Csiszar, A., & Ungvari, Z.
- Affiliations
- Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma;
- University of Oklahoma Health Sciences Center (US)
- University of Szeged (HU)
- Corresponding author
- Ungvari, Zoltan
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2017-01-01
- Volume
- 312
- Issue
- 1
- Pages
- H1-H20
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- PMC
- PMC5283909
- OpenAlex
- W2543174917
- Cited by
- 522
- References
- 315
- Citations by year
- 2026: 41 · 2025: 65 · 2024: 51 · 2023: 56 · 2022: 61 · 2021: 62 · 2020: 65 · 2019: 53 · 2018: 41 · 2017: 26
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Center for Complementary and Alternative Medicine (NCCAM) (R01-AT006526)
- HHS | NIH | National Institute on Aging (U.S. National Institute on Aging) (R01-AG047879, R01-AG038747)
- HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) (R01-NS056218)
- American Heart Association (AHA)
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Clinical Neurology › Cerebrovascular and genetic disorders
- Keywords
- cerebral autoregulation, myogenic constriction, endothelial dysfunction, neurovascular uncoupling, cerebral microvascular dysfunction, aging, Alzheimer's disease, blood-brain barrier disruption, neuroinflammation, cerebral microhemorrhages, microvascular rarefaction, cerebral ischemia, functional hyperemia, cognitive decline
- MeSH terms
- Neurovascular Coupling, Aging, Cerebrovascular Circulation, Dementia, Endothelium, Vascular, Homeostasis, Humans, Microcirculation, Cognitive Dysfunction
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