Alzheimer's disease (AD) is a major world health problem that accounts for 50% of dementia cases. At present a non-invasive in vivo diagnosis for AD is not available. The purpose of the current project has been to evaluate the diagnostic and prognostic significance of computed tomography (CT) in the study of Alzheimer disease and normal aging. A population of 349 subjects both normal and impaired has been developed during the current project. Significant gross structural and parenchymal differences were demonstrated between AD brains and normal controls. Gray-white discriminability loss was the most useful variable in the classification of AD and control studies. A major finding in this study has been the identification of distinct morphologic groups presenting with the clinical profile of Alzheimer disease. Of particular interest is the prevalence of periventricular white matter lucencies. This finding was present in 27% of AD patients and 12% of controls. We also found that 6% of the clinical AD group met CT diagnostic criteria for communicating hydrocephalus. Four per cent of study patients had CT evidence of infarction. In addition, from this study group we have obtained 23 NMR and 70 PETT studies. These pilot studies suggest that NMR-CT-PETT techniques will provide diagnostic information regarding the morphologic groups in question. We have also conducted eight neuropathologic examinations at the two-year mark of this study. The observed heterogeneity of the AD groups warrants a renewal effort to specifically investigate the CT subgroups identified and their natural history. We propose to perform 122 examinations including 75 longitudinal studies in year one. All subjects will receive CT and a subset will also receive NMR. 137 examinations including 90 longitudinal studies will be performed in years two (2) and three (3). Finally, an effort will be made to enroll patients in the neuropathology study. These studies we feel will contribute greatly to our understanding of the normal aging process and the dementing disorders of aging.
