title: Impaired neurovascular coupling in aging and Alzheimer's disease: Contribution of astrocyte dysfunction and endothelial impairment to cognitive decline.
abstract: The importance of (micro)vascular contributions to cognitive impairment and dementia (VCID) in aging cannot be overemphasized, and the pathogenesis and prevention of age-related cerebromicrovascular pathologies are a subject of intensive research. In particular, aging impairs the increase in cerebral blood flow triggered by neural activation (termed neurovascular coupling or functional hyperemia), a critical mechanism that matches oxygen and nutrient delivery with the increased demands in active brain regions. From epidemiological, clinical and experimental studies the picture emerges of a complex functional impairment of cerebral microvessels and astrocytes, which likely contribute to neurovascular dysfunction and cognitive decline in aging and in age-related neurodegenerative diseases. This overview discusses age-related alterations in neurovascular coupling responses responsible for impaired functional hyperemia. The mechanisms and consequences of astrocyte dysfunction (including potential alteration of astrocytic endfeet calcium signaling, dysregulation of eicosanoid gliotransmitters and astrocyte energetics) and functional impairment of the microvascular endothelium are explored. Age-related mechanisms (cellular oxidative stress, senescence, circulating IGF-1 deficiency) impairing the function of cells of the neurovascular unit are discussed and the evidence for the causal role of neurovascular uncoupling in cognitive decline is critically examined.
authors.affiliation: Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tarantini
authors.affiliation: Hotchkiss Brain Institute, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Cam Ha T
authors.initials: CHT
authors.lastname: Tran
authors.affiliation: Hotchkiss Brain Institute, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Grant R
authors.initials: GR
authors.lastname: Gordon
authors.affiliation: Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari
authors.affiliation: Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address: anna-csiszar@ouhsc.edu.
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D020013:Calcium Signaling; D016922:Cellular Senescence; D002560:Cerebrovascular Circulation; D003071:Cognition; D003072:Cognition Disorders / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D000066492:Cognitive Aging; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008833:Microcirculation; D000069336:Neurovascular Coupling; D018384:Oxidative Stress
chemical_list: C583557:IGF1 protein, human; D007334:Insulin-Like Growth Factor I
keywords: Cerebral circulation; Cerebrovascular; Functional hyperemia; Geroscience; Microcirculation; Neurovascular coupling; Senescence; VCI; VCID; Vascular aging