The primary objective of this five year program project grant proposal is to identify reliable and valid diagnostic markers that, relatively early in the course of the disease, will allow the differentiation of patients with Alzheimer's Disease (AD) from those who have other types of dementia of aging. We also intend to establish valid prognostic indicators which can be used, in the early stage of the disease, to predict its course and outcome. We propose a multidisciplinary, longitudinal program in which we will evaluate behavioral, intellectual, neuroradiological, neurochemical, neurophysiological and neuropathological changes associated with various forms of dementia and the interrelationships between these changes. We will be able to provide a well documented description of the natural course of AD and related dementias that in the future will allow an early diagnosis and prognosis for aging demented individuals. We will follow 200 patients presenting with symptoms of dementia and 100 appropriately matched controls over a 3-year period with periodic evaluations at 9-month intervals. At the end of the study, we will perform retrospective analysis of the behavioral, neurophysiological (EEG and evoked potentials), neuroradiological (CT Scan), neurochemical, cerebral blood flow (Xenon enhanced CT Scan), and neuropathological (autopsy, and when available, biopsy) results, to determine the extent to which each discriminates different forms of dementia. """"""""Clinical outcome"""""""" diagnoses will be made by 2 independent panels of experts who, at the end of the study will be given the relevant clinical information concerning the course of the disease in each patient. """"""""Pathological"""""""" diagnoses will be based on post mortem examination and, when available, on biopsy material, which altogether should be obtained in about 30% of our demented subjects. This information will be used to independently validate the clinical outcome diagnosis. The program consists of four separate but closely related projects sharing the general hypothesis that retrospective analysis of the data will reveal different patterns of impairment in the various subgroups. This data will serve, in the future, as criteria by which to distinguish the different etiologies of dementia.
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