Abstract
To evaluate the contribution of cholinergic deafferentation to the neural metabolic dysfunction we compared the ability of muscarinic blockade in normal elderly humans to replicate the brain hypometabolic pattern found in Alzheimer’s disease (AD). Positron Emission Tomography (PET) scans following 18F-fluorodeoxyglucose administration were performed in nine unmedicated AD patients studied once under placebo and in nine age-matched normal volunteers studied twice during placebo and scopolamine treatment administered in blind fashion and randomized order. Analysis of the cortical and subcortical PET data, based on anatomic boundaries defined by magnetic resonance imaging scans, evidenced in AD patients metabolic decrements of 14 to 19% in frontal, temporal, cingulate and parietal cortex, insula and substantia nigra. In contrast, scopolamine given to normal volunteers at a dose that induced memory impairment, increased metabolism in all cortical areas and several subcortical regions by 11 to 21%. This distribution bore no resemblance to the pattern of brain hypofunction found in patients with AD. Global muscarinic blockade in humans thus does not appear to mimic the pattern of cerebral hypofunction found in AD. Analysis of small structures, such as substantia nigra, amygdala and hippocampus, showed discrepancies between the known brain lesions and the metabolic response of these structures to AD and to scopolamine. These findings suggest that a neurotransmission component (muscarinic receptor subtype or another neurotransmission) may play a significant role in the brain metabolic pattern of AD.
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Blin, J., Chase, T.N., Piercey, M.F. (1995). Do the Effects of Muscarinic Receptor Blockade on Brain Glucose Consumption Mimic the Cortical and Subcortical Metabolic Pattern of Alzheimer’s Disease in Normal Volunteers ?. In: Comar, D. (eds) PET for Drug Development and Evaluation. Developments in Nuclear Medicine, vol 26. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-0429-6_11
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DOI: https://doi.org/10.1007/978-94-011-0429-6_11
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