Plasma Amyloid-β as a Function of Age, Level of Intellectual Disability, and Presence of Dementia in Down Syndrome

Abstract

Adults with Down syndrome (DS) are at risk for developing Alzheimer disease (AD). While plasma Aβ is known to be elevated in DS, its relationship to cognitive functioning is unknown. To assess this relationship, samples from two groups of subjects were used. In the first group, nondemented adults with DS were compared to: 1) a group of young and old individuals without DS and 2) to a group of patients with AD. Compared to these controls, there were significantly higher levels of plasma Aβ in nondemented adults with DS while AD patients showed lower levels of plasma Aβ. A larger second group included demented and nondemented adults with DS, in order to test the hypothesis that plasma Aβ may vary as a function of dementia and ApoE genotype. Plasma Aβ levels alone did not dissociate DS adults with and without dementia. However, in demented adults with DS, ApoE4 was associated with higher Aβ40 but not Aβ42. After controlling for level of intellectual disability (mild, moderate, profound) and the presence or absence of dementia, there was an improved prediction of neuropsychological scores by plasma Aβ. In summary, plasma Aβ can help predict cognitive function in adults with DS independently of the presence or absence of dementia.

Frontal Lobe Degeneration in Adults with Down Syndrome and Alzheimer's Disease: A Review

“…In one study, the results of the cognitive assessments were available only as supplemental data [46]. Three other studies reported no objective data from cognitive assessments [39,41,42]. In another 3 studies, it was necessary to refer to earlier studies by the same group in order to determine which cognitive assessment instruments were used [39,42,43].…”

“…Of the 14 studies, only 2 focused on the cognitive assessment of individuals with DS and AD [20,36]. There were 11 studies in which the main focus was AD in DS [12,20,35,36,37,38,39,40,41,42,43]; there was 1 study in which the central theme was functional aspects of AD in adults with intellectual disability [44], and there were 2 studies that focused on aging individuals with DS but not necessarily on aspects related to dementia [45,46]. Of the 11 studies focusing on AD in DS, 2 included only subjects diagnosed with DS and AD [12,37], whereas the others involved control groups of individuals without AD, without DS, or even without intellectual disabilities.…”

“…Hanney et al [40] conducted an experimental study of the use of memantine (an N-methyl D -aspartate receptor antagonist used in treating the symptoms of AD) in individuals with DS. Two studies explored the relationships between plasma Aβ, AD, and DS, one focusing on whether plasma Aβ level is associated with cognitive functions [41] and the other focusing on whether plasma Aβ level is associated with early-onset dementia [42]. Oliver et al [43] examined the impact of behavioral changes in individuals with DS and AD, comparing it with that observed for individuals with DS and no dementia.…”

“…However, after detailed analysis of the articles, 3 were excluded: 1 was excluded because it was a postmortem analysis [32], and 2 were excluded because they did not address the diagnosis or signs of dementia [33,34], although 1 of those 2 did address the relationship between oxidative stress and a decline in memory [34]. Therefore, we reviewed 14 articles [12,20,35,36,37,38,39,40,41,42,43,44,45,46], all of which are profiled in table 1. Although we would have included studies available in English, Spanish, Italian, or Portuguese, from the 14 studies, only 1 was in Spanish, the other ones were all in English.…”

“…In this review, we identified 3 studies that employed instruments specific for the assessment of executive functions [20,43,45]. Eight of the selected studies used screening instruments specific for the assessment of attention [35,37,38,39,40,41,42,45]. In the study conducted by Esteba-Castillo et al [35], abstract thought was evaluated with the Cambridge Cognitive Examination adapted for persons with Down syndrome or other intellectual disabilities.…”