Cerebral and Cardiac Vascular Pathology in Alzheimer’s Disease



A large body of evidence now indicates that Alzheimer’s disease (AD) is a vascular disorder with neurodegenerative consequences and should be treated as such. Vascular risk factors in the elderly individual who already possesses a dwindling cerebrovascular reserve due to advancing age contribute to a further decline in cerebral blood flow (CBF) that results in unrelenting brain hypoperfusion. Brain hypoperfusion, in turn, gives rise to reduced ATP synthesis, thereby provoking a metabolic energy crisis involving ischemic-sensitive neurons and glial cells. Neuronal energy compromise accelerates oxidative stress, excess production of reactive oxygen species, aberrant protein synthesis, ionic pump dysfunction, signal transduction impairment, neurotransmitter failure, abnormal processing of amyloid-β protein precursor giving rise to amyloid-β deposition, and microtubule disruption from tau hyperphosphorylation. All high-energy metabolic changes leading to oxidative stress and cellular hypometabolism precede clinical expression of AD. Regional CBF measurements using neuroimaging techniques such as PET, SPECT, echocardiography, and Doppler ultrasound can help predict AD preclinically at the mild cognitive impairment stage or even before any clinical expression of the dementia is detected. Epidemiological studies together with findings from preclinical detection tools and present-day treatments for AD are proof of concept that AD is a vascular disorder that results in brain hypoperfusion. Both peripheral and cerebral vascular pathology can contribute to brain hypoperfusion. This new paradigm prompts redirection of our thinking and our efforts to decisively manage and treat 25 million people worldwide afflicted with this disorder.


Cerebral Blood Flow Mild Cognitive Impairment Vascular Risk Factor Cerebral Hypoperfusion Brain Hypoperfusion 
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This research was supported by an Investigator-Initiated Research Grant from the Alzheimer’s Association.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.NWGig Harbor

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