The major long-term objective of this research is to provide a safe, noninvasive, cost-effective neurobiological method of identifying and distinguishing Alzheimer's Disease from multi- infarct dementia and depression. Currently, the differential diagnosis of Alzheimer's disease is presumptive, costly, time consuming, and frequently inaccurate with the only unequivocal diagnoses coming from examination of brain tissue. The current project is designed as the first step in determining whether the measurement of cortical regional cerebral blood flow via the 133Xe inhalation technique can serve as a diagnostic as well as a prognostic method. Another objective is to study the changes in dynamic cortical functioning during the progressive course of Alzheimer's disease, multi-infarct dementia and depression. Such data could be of prognostic value. Successful completion of this research would add a cost effective, noninvasive neurobiological tool to the differential diagnostic battery. In this initial project, groups of patients with Alzheimer's disease, multi-infarct dementia, depression and unimpaired subjects will undergo rCBF measurements during rest and memory tasks on a minimum of four occasions: initial, and annually thereafter. Each patient/subject will also undergo a comprehensive neuropsychological test battery and a neurological examination of the day of each of these measurements. Resting and activated rCBF will be analyzed to determine if there are unique blood flow patterns for the respective disorders. The neuropsychological test data will be correlated with resting and activated flow to further elucidate brain-behavior relationships during the course of each disorder. The patients/subjects studied in this protocol will continue to be followed, through subsequent research projects, throughout the course of their respective disorders with definitive diagnoses being obtained via autopsy whenever possible.
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