Positron emission tomography in Alzheimer's disease in relation to disease pathogenesis: a critical review.
PET studies of brain metabolism and blood flow in Alzheimer's disease (AD) patients lead to the following conclusions: (a) Reductions in "resting state" regional brain metabolism are roughly proportional to dementia severity. (b) These reductions are greater in association than in primary sensory and motor neocortical regions, and correlate with the distribution of neuropathology and cell loss postmortem. (c) Demented but not nondemented Down syndrome adults also have worse metabolic reductions in the association than primary neocortices, suggesting an equivalent pathological process in demented Down syndrome and AD patients. (d) Brain metabolic patterns in AD patients are heterogeneous, belonging to at least four distinct metabolic groups that correspond to different patterns of cognitive and behavioral abnormalities; the metabolic patterns have not been shown to be related to disease etiology. (e) Abnormal right-left metabolic asymmetries in mildly demented AD patients can retain their initial directions for as long as 48 months; these asymmetries precede and predict the cognitive "discrepancies" that later appear, such that moderately demented patients with disproportionate visuospatial compared with language deficits, or disproportionate visual recall compared with verbal recall, have a greater metabolic reduction in the right than left hemisphere, and vice versa. (f) Parietal association/frontal association metabolic ratios also retain their direction over time; in moderately demented patients, relative hypometabolism in the prefrontal association cortex is related to deficits in verbal fluency and attention to simple sets, whereas relative hypometabolism in the parietal association cortex correlates with failure in arithmetic, verbal comprehension, drawing, and immediate memory for visuospatial location. (g) Although metabolically spared compared with the association cortices, the primary sensory cortices, basal ganglia, thalamus, and cerebellar hemispheres show metabolic declines in AD using high-resolution PET scanners, possibly due to their connections with more pathologically affected regions. (h) Early metabolic deficits in AD are hypothesized to arise from synaptic failure in association cortical areas; such failure in the occipitotemporal visual cortex can be reversed in mildly to moderately demented AD patients who are capable of performing a face-matching task.
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Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892.
D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D000818:Animals; D006801:Humans; D014055:Tomography, Emission-Computed