Cognitive Deficits and Local Metabolic Changes in Dementia of the Alzheimer Type

Abstract

Relations between neuropsychological and regional cerebral metabolic alterations were studied cross-sectionally and longitudinally in patients with dementia of the Alzheimer type and were compared to controls. Reductions in regional cerebral metabolism, measured in the resting state with positron emission tomography and [18F]fluorodeoxyglucose, were greatest in the association cortices relative to the primary sensory and motor cortices and to the thalamus and basal ganglia. Individual patients demonstrated different patterns of association cortex metabolic reductions. Reductions in homologous right and left hemisphere association regions were often asymmetric. Parietal and frontal metabolic reductions were also often disproportionate relative to each other. Neuropsychological impairments in patients with dementia of the Alzheimer type were also selective and heterogeneous. Memory impairment was often the first symptom followed by impaired ability to maintain attention to complex or shifting sets. As the disease progressed, language and visuospatial functions became impaired. Whereas the memory impairment was usually global and severe, patterns of nonmemory impairments varied markedly from patient to patient. For example, some patients had disproportionately severe language impairments relative to milder visuospatial impairments and other patients demonstrated the opposite pattern. In patients with moderate dementia of the Alzheimer type, patterns of nonmemory impairments were related to the distribution of association cortex metabolic reductions. At initial evaluation, mildly impaired patients did not have significant nonmemory language and visuospatial impairments but did have significant neocortical metabolic reductions that were not correlated with neuropsychological test scores. After a mean of 2 years of longitudinal study, significant language and visuospatial impairments developed, and right-left metabolic asymmetries were significantly correlated with visuospatial-language discrepancies. These results suggest that neocortical metabolic abnormalities can be observed with positron emission tomography before associated impairments of neocortically mediated visuospatial and language functions are demonstrable.