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Functional brain imaging in the resting state and during activation in Alzheimer's disease. Implications for disease mechanisms involving oxidative phosphorylation.

Authors
Type
Published Article
Journal
Annals of the New York Academy of Sciences
Publication Date
Volume
893
Pages
138–153
Identifiers
PMID: 10672235
Source
Medline
License
Unknown

Abstract

In vivo brain imaging of patients with Alzheimer's disease (AD) using positron emission tomography (PET) demonstrates progressive reductions in resting-state brain glucose metabolism and blood flow in relation to dementia severity, more so in association than primary cortical regions. During cognitive or psychophysical stimulation, blood flow and metabolism in the affected regions can increase to the same extent in mildly demented AD patients as in age-matched controls, suggesting that energy delivery is not rate limiting. Activation declines with dementia severity, and is markedly reduced in severely demented patients. These results suggest that there is an initial "normal" functionally-responsive stage in AD, followed by a late less responsive stage. Studies of biopsied and postmortem brain indicate that the initial stage is accompanied by selective and potentially reversible down-regulation of the brain enzymes, including cytochrome oxidase, which mediate mitochondrial oxidative-phosphorylation.

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