Ninety-six individuals with Down syndrome over age 35 years were evaluated and followed up for evidence of nontreatable dementia. Dementia was judged to be present when a functional decline occurred in areas such as orientation, memory, verbal and motor skills, and self-care abilities. Forty-nine patients with Down syndrome fit this criterion, with an average onset of dementia at 54.2 +/- 6.1 years. The prevalence of dementia in the institutionalized Down syndrome population of our study (n = 53) was 8% (2/25 patients) between 35 and 49 years, 55% (11/20 patients) between 50 and 59 years, and 75% (6/8 patients) of those over 60 years old. Of note, 41 (84%) demented individuals with Down syndrome developed seizures. Ten (20%) had parkinsonian features. Adequately treated hypothyroidism was present in 27 (59%) of 46 demented patients with Down syndrome tested. The average duration of dementia in the 23 patients who died was 4.6 +/- 3.2 years. Computed tomographic scans in 43 patients all showed brain tissue loss, most pronounced in the temporal lobes. Brains from 12 autopsied cases showed large numbers of plaques and tangles in the same locations as in persons with Alzheimer disease.