OBJECTIVES: To examine the correlations between senile lesion densities and development of dementia symptoms in very old people. To perform a quantitative neuropathologic evaluation of several cortical and subcortical areas in a series of 29 nonagenarians and centenarians. PATIENTS: Ten patients with no cognitive impairment and 19 patients with clinically overt Alzheimer's disease. DESIGN: Neuropathologic case series. Severity of Alzheimer's disease was assessed with the Mini-Mental State examination and by postmortem chart review using the extended Clinical Dementia Rating Scale. Comparisons between neurofibrillary tangle and senile plaque densities in demented and nondemented individuals were performed by analysis of covariance controlling for age at the time of death. SETTING: Studies were conducted at the Psychiatric and Geriatric hospitals of the University of Geneva School of Medicine in Geneva, Switzerland. MAIN OUTCOME MEASURE: Correlations between clinical diagnosis and severity of Alzheimer's disease and neuropathologic change densities. RESULTS: Statistically significant differences were found in neurofibrillary tangle densities in the superior parietal, superior temporal, anterior and posterior cingulate cortex, and nucleus basalis of Meynert between nondemented and Alzheimer's disease cases. The superior parietal and posterior cingulate cortex contained significantly higher senile plaque counts in demented compared with nondemented cases. In contrast to younger demented cases, the number of senile plaques in the neocortex was correlated with the severity of dementia in centenarians. CONCLUSIONS: These results indicate that the neuronal degeneration in very old demented patients involves cortical areas usually preserved at the early stages of the dementing process. Senile plaque formation in certain neocortical areas may be a pathologic hallmark of the severity of dementia in this particular age group.