Individuals with Down syndrome develop neuropathologic and in some cases clinical evidence of Alzheimer disease after age 40. We compared CT scans of 18 Down syndrome subjects, 26-70 years old (seven of whom satisfied criteria for dementia), with 175 screened normal volunteer control subjects for evidence of cortical and subcortical atrophy. CT scans were analyzed as a function of age and cognitive status. The suprasellar cistern ratio, presumed to measure mesial temporal-lobe atrophy (or hypoplasia), was correlated with severity of cognitive impairment, even when age effects were removed. The suprasellar cistern ratio predicted dementia status with an accuracy of greater than 75%. Brain measurements on CT scans showed a distinct pattern of increased abnormality with age in patients with Down syndrome; this differed clearly from that seen in controls.