With new developments in quantitative magnetic resonance imaging (MRI) techniques, it is now possible to detect and quantify, in vivo, the pattern of anatomical pathology during different stages of degenerative diseases. With the use of such techniques, the proposed research is designed to investigate the anatomical and functional progression of AD in vivo. The project has three major goals. The first is to determine longitudinally, in each individual, with serial MRI scans and quantitative volumetric analysis, the earliest sites of anatomical pathology in AD and the pattern of spread of such pathology. The second goal is to utilize recently developed electrophysiological measures to assess the functional integrity of structures known to be affected in AD. By again employing a longitudinal design we will determine if functional alterations detected electrophysiologically precede the appearance of structural damage in specific brain regions. Can long-latency evoked potentials generated in known anatomical sites provide an early marker for the onset of disease in particular cerebral circuit s? The third goal is to relate the appearance of characteristic behavioral symptoms and their sequence of development with the progressive encroachment of the disease process into well defined ganglionic regions. Achievement of these goals will be enormously facilitated by the opportunity to study patients longitudinally and to combine in vivo quantitative anatomy with behavioral and electrophysiological measures. Research on the anatomical and functional progression of AD is important for an understanding of the pathophysiology of the disease. In addition, the delineation of the anatomical pathology of AD would be helpful for the design of interventional strategies. More importantly, if an electrophysiological marker can be developed that reliably predicts the anatomical pathology, this will earlier measure may allow intervention at a time when reversibility or interruption of progression is most feasible.