Sequence of cognitive decline in dementia in adults with Down's syndrome

Adults with Down's syndrome (DS) are known to be at risk of dementia of the Alzheimer type (DAT), but because of their lifelong intellectual deficits, it is difficult to determine the earliest signs and characteristics of age-associated decline and dementia. In a longitudinal study in which all participants were healthy at the time of their entry into the study, the present authors compared the amount of decline on the subtests of the WISC-R to determine the sequence of cognitive decline associated with varying stages of dementia. Twenty-two individuals with varying degrees of cognitive decline were compared to 44 adults with DS who have remained healthy. All participants functioned in the mild or moderate range of intellectual disability at initial testing. On each subtest of the WISC-R, the amount of change experienced by the healthy participants over the study period was compared to the amount of change found for each of the groups with decline. Out of the individuals who showed declines, 10 adults with DS were classified as having 'questionable' decline based on the presence of memory impairment, and five and seven adults with DS were classified as in the 'early stage' and 'middle stage' of DAT, respectively, based on the presence of memory impairment, score on the Dementia Scale for Down Syndrome and a physician's diagnosis. It was found that participants who were identified as 'questionable', in addition to the memory loss that determined their classification, also showed significant declines on the Block Design and Coding subtests. The five adults in the early stage of dementia showed declines on these subtests, and in addition, on the Object Assembly, Picture Completion, Arithmetic and Comprehension subtests. The seven adults in the middle stage of dementia showed declines on these subtests, plus declines on Information, Vocabulary and Digit Span subtests. The Picture Arrangement and Similarities subtests were not useful in distinguishing between the groups because of baseline floor effects for a substantial proportion of participants. The present longitudinal study showed a sequence of cognitive decline associated with DAT, beginning with a possible 'pre-clinical' stage, and progressing through the early and middle stages. This approach begins to define the sequence of declining cognitive capacities that contributes to the observed functional deterioration caused by Alzheimer's disease and that is likely to reflect the involvement of cortical areas as the disease progresses.