Dataset Information

Comparison of longitudinal A? in nondemented elderly and Down syndrome.

ABSTRACT: Down syndrome (DS) predisposes individuals to early Alzheimer's disease (AD). Using Pittsburgh Compound B ([11C]PiB), a pattern of striatal amyloid beta (A?) that is elevated relative to neocortical binding has been reported, similar to that of nondemented autosomal dominant AD mutation carriers. However, it is not known whether changes in striatal and neocortical [11C]PiB retention differ over time in a nondemented DS population when compared to changes in a nondemented elderly (NDE) population. The purpose of this work was to assess longitudinal changes in trajectories of A? in a nondemented DS compared to an NDE cohort. The regional trajectories for anterior ventral striatum (AVS), frontal cortex, and precuneus [11C]PiB retention were explored over time using linear mixed effects models with fixed effects of time, cohort, and time-by-cohort interactions and subject as random effects. Significant differences between DS and NDE cohort trajectories for all 3 region of interests were observed (p < 0.05), with the DS cohort showing a faster accumulation in the AVS and slower accumulation in the frontal cortex and precuneus compared to the NDE cohort. These data add to the previously reported distinct pattern of early striatal deposition not commonly seen in sporadic AD by demonstrating that individuals with DS may also accumulate A? at a rate faster in the AVS when compared to NDE subjects.

SUBMITTER: Tudorascu DL

PROVIDER: S-EPMC6251757 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Comparison of longitudinal Aβ in nondemented elderly and Down syndrome.

Tudorascu Dana L DL Anderson Stewart J SJ Minhas Davneet S DS Yu Zheming Z Comer Diane D Lao Patrick P Hartley Sigan S Laymon Charles M CM Snitz Beth E BE Lopresti Brian J BJ Johnson Sterling S Price Julie C JC Mathis Chester A CA Aizenstein Howard J HJ Klunk William E WE Handen Benjamin L BL Christian Brad T BT Cohen Ann D AD

Neurobiology of aging 20180927

Down syndrome (DS) predisposes individuals to early Alzheimer's disease (AD). Using Pittsburgh Compound B ([<sup>11</sup>C]PiB), a pattern of striatal amyloid beta (Aβ) that is elevated relative to neocortical binding has been reported, similar to that of nondemented autosomal dominant AD mutation carriers. However, it is not known whether changes in striatal and neocortical [<sup>11</sup>C]PiB retention differ over time in a nondemented DS population when compared to changes in a nondemented el ...[more]

PMID: 30359879

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Project description:ImportanceRecent studies show that cerebral β-amyloid (Aβ) deposition is associated with blood pressure and measures of arterial stiffness in nondemented individuals.ObjectiveTo examine the association between measures of arterial stiffness and change in Aβ deposition over time.Design, setting, and participantsDeposition of Aβ was determined in a longitudinal observational study of aging by positron emission tomography using the Pittsburgh compound B twice 2 years apart in 81 nondemented individuals 83 years and older. Arterial stiffness was measured with a noninvasive and automated waveform analyzer at the time closest to the second positron emission tomography scan. All measures were performed under standardized conditions. Pulse wave velocity (PWV) was measured in the central (carotid-femoral and heart-femoral PWV), peripheral (femoral-ankle PWV), and mixed (brachial-ankle PWV) vascular beds.Main outcomes and measuresThe change in Aβ deposition over 2 years was calculated from the 81 individuals with repeat Aβ-positron emission tomography.ResultsThe proportion of Aβ-positive individuals increased from 48% at baseline to 75% at follow-up. Brachial-ankle PWV was significantly higher among Aβ-positive participants at baseline and follow-up. Femoral-ankle PWV was only higher among Aβ-positive participants at follow-up. Measures of central stiffness and blood pressure were not associated with Aβ status at baseline or follow-up, but central stiffness was associated with a change in Aβ deposition over time. Each standard deviation increase in central stiffness (carotid-femoral PWV, P = .001; heart-femoral PWV, P = .004) was linked with increases in Aβ deposition over 2 years.Conclusions and relevanceThis study showed that Aβ deposition increases with age in nondemented individuals and that arterial stiffness is strongly associated with the progressive deposition of Aβ in the brain, especially in this age group. The association between Aβ deposition changes over time and generalized arterial stiffness indicated a relationship between the severity of subclinical vascular disease and progressive cerebral Aβ deposition.

Project description:Down syndrome (DS) is associated with intellectual disability and an ultra-high risk of developing dementia. Informant ratings are invaluable to assess abilities and related changes in adults with DS, particularly for those with more severe intellectual disabilities and/or cognitive decline. We previously developed the informant rated Cognitive Scale for Down Syndrome (CS-DS) to measure everyday cognitive abilities across memory, executive function, and language domains in adults with DS, finding CS-DS scores are a valid measure of general abilities, and are significantly lower for those with noticeable cognitive decline compared to those without decline. To further test the validity of the CS-DS in detecting changes associated with cognitive decline we collected longitudinal data across two time points, approximately 1.5-2 years apart, for 48 adults with DS aged 36 years and over. CS-DS total scores (78.83 ± 23.85 vs. 73.83 ± 25.35, p = 0.042) and executive function scores (46.40 ± 13.59 vs. 43.54 ± 13.60, p = 0.048) significantly decreased between the two time points, with scores in the memory domain trending towards a significant decrease (22.19 ± 8.03 vs. 20.81 ± 8.63, p = 0.064). Adults with noticeable cognitive decline at follow-up showed a trend to significantly greater change in total scores (7.81 ± 16.41 vs. 3.59 ± 16.79, p = 0.067) and significantly greater change in executive function scores (5.13 ± 9.22 vs. 1.72 ± 9.97, p = 0.028) compared to those without decline. Change in total scores showed significant correlations with change in scores from other informant measures of everyday adaptive abilities and symptoms associated with dementia, and participant assessment of general cognitive abilities (all p < 0.005), while change in memory scores (R 2 = 0.28, p = 0.001) better predicted change in participant cognitive assessment scores than change in executive function (R 2 = 0.15, p = 0.016) or language (R 2 = 0.15, p = 0.018) scores. These results suggest informants may better detect changes in the executive function domain, while change in informant rated memory scores best predicts change in assessed cognitive ability. Alternatively, memory domain scores may be sensitive to changes across both early and late cognitive decline, whereas executive function domain scores are more sensitive to changes associated with later noticeable cognitive decline. Our results provide further support for the validity of the CS-DS to assess everyday cognitive abilities and to detect associated longitudinal changes in individuals with DS.

Project description:IntroductionThe present study provides longitudinal data on the development of receptive and expressive grammar in children and adolescents with Down syndrome and addresses the role of nonverbal cognitive abilities and verbal short-term memory for morphosyntactic development.MethodSeventeen German-speaking individuals with Down syndrome (aged 4;6-17;1 years at first testing (T1)) were assessed twice, 4;4-6;6 years apart. For a subset of five participants, there was also a third assessment 2 years after the second. Receptive grammar, nonverbal cognition, and verbal short-term memory were tested using standardized measures. For expressive grammar, elicitation tasks were used to assess the production of subject-verb agreement and of wh-questions.ResultsAt group level, the participants showed a significant increase in grammar comprehension from T1 to T2. However, progress diminished with increasing chronological age. Notable growth could not be observed beyond the age of 10 years.With respect to expressive grammatical abilities, progress was limited to those participants who had mastered verbal agreement inflection around age 10 years. Individuals who did not master verbal agreement by late childhood achieved no progress in producing wh-questions, either.There was an increase in nonverbal cognitive abilities in the majority of participants. Results for verbal short-term memory followed a similar pattern as those for grammar comprehension. Finally, neither nonverbal cognition nor verbal short-term memory were related to changes in receptive or expressive grammar.DiscussionThe results point to a slowdown in the acquisition of receptive grammar which starts before the teenage years. For expressive grammar, improvement in wh-question production only occurred in individuals with good performance in subject-verb agreement marking, which suggests that the latter might have a trigger function for further grammatical development in German-speaking individuals with Down syndrome. The study provides no indication that nonverbal cognitive abilities or verbal short-term memory performance determined the receptive or expressive development. The results lead to clinical implications for language therapy.

Dataset Information

Comparison of longitudinal A? in nondemented elderly and Down syndrome.

Publications

Comparison of longitudinal Aβ in nondemented elderly and Down syndrome.

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