Dementia is a leading cause of disability among the elderly, with a prevalence rate of 15% in individuals over age 65. This study is designed to investigate changes in cerebral structure and function associated with normal aging and dementia. An understanding of these mechanisms will help in developing strategies to prevent, diagnose, and treat cognitive deterioration in the aging population. The immediate objectives are to: (1) evaluate global and regional changes in cerebral blood flow (CBF) in aging and dementia; (2) investigate the relationship between abnormalities in CBF and psychological deficits in dementia; (3) assess the effects of stimulation with specific cognitive tasks on BCF in normal aging and dementia; (4) study the relationship between cerebral atrophy and CBF reductions in the elderly; and (5) describe regional 31P-NMR spectroscopic patterns in various age groups and dementia sub-types (Alzheimer's type, multi-infarct, and Parkinsonian). Regional cerebral blood flow will be measured using the intravenous Xenon-133 injection technique, which has the advantages of non-invasiveness, established and reproducible quantification methods, validity when applied to an aged population, and ease of implementation in activation studies. Subjects will be rigorously evaluated for the presence of cerebrovascular risk factors including asymptomatic carotid artery disease assessed non-invasively, in order to separate the effect of vascular changes from primary parenchymal degeneration as a cause of CBF reduction in aging. Proton-NMR imaging will be used as a new and promising technique for assessing cerebral atrophy and changes of multi-infarct dementia (MID). An even newer development, in vivo 31P-NMR spectroscopy, will be employed to measure regional variations in phosphate-dependent bioenergetics. All global and regional physiological and anatomical data will be correlated with the general and specific psychological deficits in these subjects. The information thus gained may improve our understanding of underlying pathophysiological processes in disorders of aging, and direct future efforts to develop effective therapeutic modalities.
