The cognitive and neurophysiological effects of healthy aging and age-related dementias were investigated using standard neuropsychological tests, measures of component cognitive processing, and positron emission tomography with 18-F Fluoro-2-D-deoxyglucose. Healthy aging was associated with a specific pattern of cerebral metabolism (rCMRglc) showing frontal hypometabolism with relative increased activity in parieto-occipital association areas, basal ganglia, midbrain, and cerebellum. Two cerebral metabolic patterns characteristic of (dementia of the Alzheimer-type (DAT) were identified using regional covariance analysis of resting state rCMRglc. Expression of these patterns distinguished DAT patients from patients with frontotemporal dementia and were correlated with specific cognitive deficits in the DAT group. Premorbid intellectual ability was inversely correlated with rCMRglc in several regions of association cortex in DAT patients. Among DAT patients, early age at onset of dementia was related to greater impairment on measures of visuospatial function. DAT patients with a family history of dementia showed greater rCMRglc deficits in the frontal association regions. Further, a unique neuropsychological profile was observed for a subgroup of DAT patients with early prominent visual disturbances characterized by severe visuospatial difficulties but better memory performance than typical DAT patients. Studies of complex attention in DAT identified three similar impairments of shifting or divided attention. A measure of visuospatial attention during visual search showed incremental slowing of reaction time with parametric increases in attentional distracters. DAT patients showed less benefit than controls with decreasing cue size in a visual search task. Long-term memory and orientation decline with age among non-demented Down syndrome adults.
