A clinical prospective study of dementia of the Alzheimer type in 96 individuals with Down syndrome over age 35 years is reported from the Eunice Kennedy Shriver Center, Waltham, MA and the Massachusetts General Hospital and Harvard Medical School, Boston, MA. Approximately 50% had a clinical dementia and the average age at dementia onset was 54.2 years. The prevalence of dementia in institutionalized Down syndrome population in this study was 8% between 35 and 49 years, 55% between 50 and 59 years, and 75% of those over 60 years old. Seizures developed in 84% of demented individuals with Down syndrome and 20% had Parkinsonian features. Hypothyroidism had been treated in 59% of the demented patients. CT scans showed brain tissue loss most pronounced in the temporal lobes. Neuropathological examination of 12 autopsied demented cases of Down syndrome showed gyral and central atrophy especially of the temporal lobes, and large numbers of plaques and tangles distributed in the same locations (i.e. hippocampus, amygdala, neocortex) as in the non-Down syndrome cases of Alzheimer dementia. [1]

COMMENT. The early age at onset of dementia in the Down syndrome population corresponds to the average age of onset (before age 52) in several large pedigrees of familial Alzheimer's disease. The gene for this form of autosomal dominant early onset Alzheimer disease has been mapped to the long arm of chromosome 21. An increased frequency of Down syndrome has been reported among relatives of early onset Alzheimer disease probands. The neuropathology and neurochemistry of Alzheimer's disease in aging individuals with Down syndrome and in the general population seem to be identical although the clinical expression of Alzheimer disease in Down syndrome shows some distinctive features, e.g. a high incidence of seizures.