Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease

Aging, hypertension, diabetes, hypoxia/obstructive sleep apnea (OSA), obesity, vitamin B12/folate deficiency, depression, and traumatic brain injury synergistically promote diverse pathological mechanisms including cerebral hypoperfusion and glucose hypometabolism. These risk factors trigger neuroinflammation and oxidative‐nitrosative stress that in turn decrease nitric oxide and enhance endothelin, Amyloid‐β deposition, cerebral amyloid angiopathy, and blood–brain barrier disruption. Proinflammatory cytokines, endothelin‐1, and oxidative‐nitrosative stress trigger several pathological feedforward and feedback loops. These upstream factors persist in the brain for decades, upregulating amyloid and tau, before the cognitive decline. These cascades lead to neuronal Ca2+ increase, neurodegeneration, cognitive/memory decline, and Alzheimer's disease (AD). However, strategies are available to attenuate cerebral hypoperfusion and glucose hypometabolism and ameliorate cognitive decline. AD is the leading cause of dementia among the elderly. There is significant evidence that pathways involving inflammation and oxidative‐nitrosative stress (ONS) play a key pathophysiological role in promoting cognitive dysfunction. Aging and several comorbid conditions mentioned above promote diverse pathologies. These include inflammation, ONS, hypoperfusion, and hypometabolism in the brain. In AD, chronic cerebral hypoperfusion and glucose hypometabolism precede decades before the cogn...
Source: Journal of Neuroscience Research - Category: Neuroscience Authors: Tags: Review Source Type: research