Increasing evidence supports the idea that chronic hypoperfusion in the brain is responsible for the pathogenesis
underling Alzheimer’s disease (AD). Obesity at midlife is associated with the risk of cognitive loss and AD at later
life. Obesity decreases cerebral blood flow that is associated with decreased synthesis and actions of nitric oxide (NO) derived
from the endothelium and also increases the production of oxidative stress. Increased plasma levels of asymmetric
dimethylarginine decreases the production of NO by inhibiting NO synthase activity, leading to cerebral hypoperfusion
and cognitive and neurodegenerative changes in AD. Adiponectin has a cerebroprotective action through an eNOSdependent
mechanism. Obesity-induced endothelial dysfunction and cerebral hypoperfusion enhance the production of
β-amyloid that in turn impairs endothelial function; this vicious cycle promotes the pathogenic changes leading to AD.
Interrupting this cycle by enhancement of NO-mediated cerebral blood flow is expected to promote prophylaxis against
AD pathogenesis. This review summarizes recent advances in prophylactic or therapeutic measures, including physical
exercise, nutritionally adequate dietary intake, pharmacological treatments such as acetylcholinesterase inhibitors and antioxidants,
and bariatric surgery that are efficient in protecting and retarding the progress of cognitive failure and neurodegeneration.
Keywords: Alzheimer's disease, β-amyloid, cerebral blood flow, endothelial function, nitric oxide, obesity.
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