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Three pairs of twins, each with proved monozygosity, were shown to be discordant for dementia of the Alzheimer's type and to have remained discordant for periods of 8 to 11 years. Dementia of the Alzheimer's type was demonstrated by history; serial clinical examinations; serial measurements of cerebral glucose utilization using positron emission tomography and of cerebral ventricular volumes and of rates of change of volumes using quantitative computed tomography; and by serial neuropsychological tests. The results of each of these measures showed no evidence of clinical abnormality in any unaffected twin. DNA markers from the proximal long arm of chromosome 21 did not distinguish between the affected and the unaffected member of any pair of identical twins. Family pedigrees were negative for Alzheimer's disease. The results suggest that environmental or other nongenetic factors contribute to Alzheimer's disease in discordant monozygotic twins, or that some cases arise by a postzygotic somatic mutation.

The course of idiopathic normal-pressure hydrocephalus was studied in a 78-year-old woman with a 4-year history of progressive dementia who underwent neuropsychologic testing, quantitative x-ray computed tomography, magnetic resonance imaging, and positron emission tomography with fludeoxyglucose F 18 to measure rates of regional cerebral glucose utilization. Preshunt cognitive testing demonstrated progressive deterioration during 2 years, and positron emission tomography showed significant reductions in regional cerebral glucose utilization of 34% to 49% as compared with age- and sex-matched control subjects in frontal, temporal, parietal, and whole brain regions. Periodic testing, carried out during a 2-year period after shunt surgery, showed steady improvement in clinical status. Parallel to the clinical changes, there was a significant reversal in neuropsychologic test scores with increased brain volume and increased regional cerebral glucose utilization in several brain regions. These results documented the considerable potential for recovery of compromised brain function in older subjects even after 4 years of progressive brain disease.

Regional cerebral metabolic rates for glucose (rCMRglc), as measured with positron emission tomography, and neuropsychological function were studied longitudinally (range, 15 to 48 months) in 11 mildly impaired patients with dementia of the Alzheimer type (DAT) and compared with results from patients with moderate and severe DAT and from controls. At initial evaluation, association cortex metabolic asymmetries were greater in patients with DAT than in controls for all dementia severities and correlated significantly with neuropsychological discrepancies between visuospatial and language abilities in patients with moderate dementia. In mildly impaired patients, right-left metabolic asymmetries in the association cortices were directionally stable and became more pronounced over time. At initial evaluation, these patients had significant impairment, relative to controls, on tests of memory and attention to complex tasks but not on tests of language and visuospatial function. Memory, attention, language, and visuospatial impairments, however, all worsened significantly over time. In mildly impaired patients, correlations between right-left metabolic asymmetries and neuropsychological discrepancies were insignificant initially but were significant at last evaluation. These results demonstrate that heterogeneous nonmemory language and visuospatial impairments in early DAT are related to and predicted by the earlier-appearing distribution of metabolic reductions in the association neocortex.

To determine if impaired dichotic performance in patients with dementia of the Alzheimer type is due to the inability to divide attention or the inability to perceive degraded auditory stimuli, we measured performance on tasks of both dichotic and degraded monotic speech materials. We also examined whether perception of degraded speech stimuli presented monaurally is related to abnormalities of temporal lobe anatomy and physiology, as we have shown for dichotic performance. Although the patients were impaired on both dichotic and monotic tests, significantly greater impairment was seen on the dichotic test. Our earlier finding of a significant relation between dichotic performance and measures of anterior temporal lobe atrophy and reduced glucose metabolism was replicated, but no significant relation was found between monotic tests and measures to temporal lobe integrity. We conclude that the inability to divide attention, rather than abnormal processing of degraded stimuli per se, is reflected in poor dichotic performance in patients with dementia of the Alzheimer type, and that dichotic performance, unlike degraded monotic perception, depends directly on the integrity of temporal cortex in these patients.

Neuropsychological function and resting regional neocortical glucose metabolism, as measured by positron-emission tomography, were studied in 22 patients with mild and moderate Alzheimer's-type dementia. Metabolic reductions in the parietal association cortex and increased left-right metabolic asymmetry were observed in patients with mild and moderate degrees of dementia. Five patients with mild dementia had no impairment of neocortically mediated neuropsychological function, yet they demonstrated these same neocortical metabolic abnormalities. Asymmetry of neocortically mediated, neuropsychological functions correlated with metabolic asymmetries in patients with moderate but not mild dementia. These results suggest that physiological dysfunction in the that physiological dysfunction in the association neocortex is evident in early Alzheimer's-type dementia before the neuropsychological consequences of that dysfunction are demonstrable.

Correlations between regional cerebral metabolic rates for glucose (rCMRglc), determined by positron emission tomography using 18F-2-deoxy-2-fluoro-D-glucose, provide a measure of the functional associations between brain regions. We compared correlations between ratios of resting rCMRglc to global brain metabolism from 14 healthy autistic men (ages, 18 to 39 years) with those from 14 matched control subjects. The autistic group showed significantly fewer large positive correlations between frontal and parietal regions, particularly those with the left inferior frontal region and its right hemispheric homologue, and significantly lower correlations of the thalamus, caudate nucleus, lenticular nucleus, and insula with frontal and parietal regions, with many correlations negative in the autistic group that were positive in the control group. These results are compatible with functionally impaired interactions between frontal/parietal regions and the neostriatum and thalamus, regions that subserve directed attention.