Cerebral hypoperfusion, capillary degeneration, and development of Alzheimer disease

Considerable clinical and experimental data have shown that cerebral perfus ion is progressively decreased during increased aging and that this decreas e in brain blood flow is significantly greater in Alzheimer disease (AD). T he authors propose that advanced aging with a comorbid condition, such as a vascular risk factor, which further decreases cerebral perfusion, promotes a critically attained threshold of cerebral hypoperfusion (CATCH). With ti me, CATCH induces brain capillary degeneration and suboptimal delivery of e nergy substrates to neuronal tissue. Because glucose is the main fuel of br ain cells, its impaired delivery, with the deficient delivery of oxygen, co mpromises neuronal stability because the supply for aerobic glycolysis fail s to meet brain tissue demand. The outcome of CATCH is a metabolic cascade that involves, among other things, mitochondrial dysfunction, oxidative str ess, decreased adenosine triphosphate production, abnormal protein synthesi s, cell ionic pump deficiency, signal transduction defects, and neurotransm ission failure. These events contribute to the progressive cognitive declin e characteristic of patients with AD, as well as regional anatomic patholog y, consisting of synaptic loss, senile plaques, neurofibrillary tangles, ti ssue atrophy, and neurodegeneration. CATCH identifies the clinical heteroge neic pattern that characterizes AD because it provides compelling evidence that any of a multitude of different etiopathophysiologic vascular risk fac tors, in the presence of advanced aging, can lead to AD. The evidence in su pport of CATCH as the pathogenic trigger of AD is crystallized in this revi ew.