Obesity-Induced Cerebral Hypoperfusion Derived from Endothelial Dysfunction: One of the Risk Factors for Alzheimer's Disease

Title:Obesity-Induced Cerebral Hypoperfusion Derived from Endothelial Dysfunction: One of the Risk Factors for Alzheimer's Disease

Volume: 11 Issue: 8

Author(s): Noboru Toda, Kazuhide Ayajiki and Tomio Okamura

Affiliation:

Keywords: Alzheimer's disease, β-amyloid, cerebral blood flow, endothelial function, nitric oxide, obesity.

Abstract: 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.

Cite this article as:

Toda Noboru, Ayajiki Kazuhide and Okamura Tomio, Obesity-Induced Cerebral Hypoperfusion Derived from Endothelial Dysfunction: One of the Risk Factors for Alzheimer's Disease, Current Alzheimer Research 2014; 11 (8) . https://dx.doi.org/10.2174/156720501108140910120456