EFFECTS OF AGING AND ALZHEIMER'S DISEASE ON BRAIN STRUCTURE AND FUNCTION

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The introduction of Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) has greatly advanced our understanding of brain function and structure in various physiological states and in many disorders of the brain. Several investigators including researchers from the University of Pennsylvania have utilized these powerful modalities to examine changes that occur in normal aging as well as in dementia. It has been noted that alteration in brain function as determined by PET precede structural changes in disorders associated with aging. However, there are conflicting reports with regard to the degree and the extent of functional and structural findings in the normally aging brain and in dementia. This is partly due to the suboptimal resolution (PET) and the limited capabilities (MRI) of the earlier instruments which prevented detailed studies of the critical sites that are affected. With the advances made in recent years, most structures of the brain are clearly delineated and their function assessed with unprecedented detail. We are proposing to study 140 normal subjects (70 males and 70 females from 20 to 89 years of age) and 80 patients with Alzheimer's Disease (40 males and 40 females from 50 to 89 years of age) over 5 years. Each subject will be admitted to the Clinical Research Center at HUP and will undergo complete neurological, psychiatric, neuropsychological and laboratory testing. In addition, detailed MR and PET images of the brain will be obtained. PET imaging will be carried out following the administration of 18F-Fluorodeoxyglucose and utilizing a unique instrument; PENN-PET. This machine allows high resolution imaging of the brain in all three planes. Although the entire brain will be examined with both modalities, special attention will be paid to the temporal lobes. The major aim of the proposed research is to answer some critical questions regarding structural and metabolic alterations that frequently take place in the temporal lobes and particularly in the hippocampal/amygdalar complex. We intend to correlate structural and metabolic changes with specific neuropsychiatric functions. We will examine the relation between the memory subprocesses with structural integrity and metabolic activity of various regions particularly within the temporal-hippocampal system and related cortical network. The information gained from this study may significantly improve our understanding of the pathophysiological processes that underlie Alzheimer's Disease.