The Natural History of Alzheimer's Disease

OBJECTIVE: We describe the sampling, initial evaluation, and final diagnostic classification of subjects enrolled in a natural history study of Alzheimer's disease (AD). DESIGN: Volunteer cohort study. SETTING: Multidisciplinary behavioral neurology research clinic. PATIENTS OR OTHER PARTICIPANTS: Three-hundred nineteen individuals were enrolled in the Alzheimer Research Program between March 1983 and March 1988. Of these, 204 were originally classified with AD, 102 were normal elderly control subjects, and 13 were considered special cases. MAIN OUTCOME MEASURES: Final consensus clinical diagnosis, final neuropathologic diagnosis, and death. RESULTS: Of the 204 patients enrolled in the study, re-review after as many as 5 years of follow-up resulted in a final clinical classification of 188 with probable AD. Seven patients were believed to have a significant vascular component to the dementia, three were found to have developed depression, and six were excluded on other clinical grounds. Neuropathologic examination of 50 brains indicated definite AD in 43. After removing these seven misdiagnosed patients, the final group of probable/definite AD totaled 181 individuals. Accuracy of the baseline clinical diagnosis relative to neuropathology was 86%, and when follow-up clinical data were considered, 91.4%. Detailed neuropsychological testing yielded high sensitivity (0.988) and specificity (0.983) to dementia. Analyses of survival time from study entry until death revealed that older patients were significantly more likely to die during follow-up, but neither sex, years of education, nor pattern of cognitive impairment were related to survival. CONCLUSIONS: These data provide the descriptive basis for future studies of this cohort. They indicate that longitudinal follow-up of demented cases increases accuracy of diagnosis, and that detailed cognitive testing aids in early classification.