The overriding questions this project will address is whether the neurochemical deficits of Alzheimer's disease (AD) extend, but to a lesser degree, to elderly patients with subtle, but detectable cognitive decline. The Recruitment Core will identify and prospectively follow a cohort of elderly patents who are likely to die with a) interact cognition and no decline in cognitive function, b)) mild cognitive decline of insufficient severity to meet NINCDS criteria for probable AD, c) early AD, and d) AD in moderate to late stages of deterioration. The Neurochemistry Project will be able to determine if specific neurochemical changes are associated wit each of these groups. We have chosen to investigate three neurochemical parameters: Choline acetyltransferase activity, somatostatin immunoreactivity, and corticotropin releasing factor immunoreactivity because these have been repeatedly shown to be profoundly depressed in late stages of AD, results that have been confirmed in our own laboratory. A finding that subjects showing cognitive decline, but not meeting NINCDS criteria for probable AD, demonstrate a neurochemical profile intermediate between that observed in controls and AD cases would strengthen the suggestion derived from the Bronx Aging Study that cognitive decline in the elderly is a likely harbinger of dementia. This would encourage pharmacologic intervention at the earliest signs of cognitive deterioration, presuming such therapy ultimately becomes available. In addition, such a finding would impact on our conceptualization of the clinical threshold for the diagnosis of probable AD, and allow, ultimately, for further refinement in NINCDS criteria for the illness. A principal goal of this project is to determine the extent to which each of the chosen neurotransmitter systems is affected in cases with mild cognitive impairments. The availability of extensive diagnostic and neuropsychiatric evaluations for these cases will permit clinico-pathologic correlative studies, as well.
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