Postmortem examination was performed on 137 residents (average age 85.5 years) of a skilled nursing facility whose mental status, memory, and functional status had been evaluated during life. Seventy-eight percent were demented using conservative criteria; 55% had characteristic Alzheimer's disease. Choline acetyltransferase and somatostatin were significantly reduced in the brains of patients with Alzheimer's disease as compared with age-matched nursing home control subjects, although the degree of the reduction was less severe than found in subjects less than 80 years of age. Ten subjects whose functional and cognitive performance was in the upper quintile of the nursing home residents, as good as or better than the performance of the upper quintile of residents without brain pathology (control subjects), showed the pathological features of mild Alzheimer's disease, with many neocortical plaques. Plaque counts were 80% of those of demented patients with Alzheimer's disease. Choline acetyltransferase and somatostatin levels were intermediate between controls and demented patients with Alzheimer's disease. The unexpected findings in these subjects were higher brain weights and greater number of neurons (greater than 90 micron 2 in a cross-sectional area in cerebral cortex) as compared to age-matched nursing home control subjects. These people may have had incipient Alzheimer's disease but escaped loss of large neurons, or alternatively, started with larger brains and more large neurons and thus might be said to have had a greater reserve.