One hundred fifty organically demented patients will be investigated by standardized neurological and psychiatric examination; specialized psychometric instruments; quantitative 16-channel electroencephalography (with pattern visual evoked response); and quantitative computerized tomographic radiography (including hippocampal thin slices). Patients will be divided clinically into Alzheimer's Disease; Multi-infarct dementia; Mixed; and Other. Seventy-five healthy people over age 75 will be surveyed similarly. Ivestigations will be repeated at intervals. By the time the project is completed the brains of 55 subjects in whom pure SDAT will have been proved post-mortem will have been analyzed by neuropathological examination; by quantitative histomorphometry and cytoarchitectonic topography of 5 cortical lesions (tangles, plaques, granulovacuoles, Hirano bodies, neuronal loss); and by biochemical assay of 5 neurotransmitter markers (ChAT, AChE, 3H-QNB, MAO, muscimol-binding) from the same 19 regions used in the morphometry. Statistical evaluations will be performed on all data. An additional 20 brains from the matched controls will provide normative data. Clinical objectives are to: (i) determine quantitatively, and set in order of significance, the relationship between specific pathologic changes and clinical phenomena; (ii) evaluate EEG and CT as means of early diagnosis of Alzheimer's Disease and indicators for its presence; (iii) evaluate pattern VER & thinslice hippocampal canning; (iv) determine specificity of EEG by comparison with metabolic encephalopathy; (v) provide a clinical discriminant function evaluating the probability of pure SDAT. Pathologic objectives are to discover: (i) which is the primary neuronal lesion, most closely associated with the degree of dementia; (ii) if the clincal picture reflects severity of diffuse neocortical damage, or rather the extent of limbic histopathology; (iii) whether the clinical parameters are due to neocortical or to limbic cholinergic depletion; and (iv) whether the cholinergic deficiency's structural basis is the neuritic plaque, the neurofibrillary tangle or the neuronal loss. Pharmacological studies of high and low affinity transport of choline in synaptosomal preparations will determine the carrier's ability to transport choline for ACh synthesis.