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The Down syndrome brain in the presence and absence of fibrillar β -amyloidosis

View Article: PubMed Central - PubMed

ABSTRACT

People with Down syndrome (DS) have a neurodevelopmentally distinct brain and invariably developed amyloid neuropathology by age 50. This cross-sectional study aimed to provide a detailed account of DS brain morphology and the changes occuring with amyloid neuropathology. Forty-six adults with DS underwent structural and amyloid imaging—the latter using Pittsburgh compound B (PIB) to stratify the cohort into PIB-positive (n = 19) and PIB-negative (n = 27). Age-matched controls (n = 30) underwent structural imaging. Group differences in deep gray matter volumetry and cortical thickness were studied. PIB-negative people with DS have neurodevelopmentally atypical brain, characterized by disproportionately thicker frontal and occipitoparietal cortex and thinner motor cortex and temporal pole with larger putamina and smaller hippocampi than controls. In the presence of amyloid neuropathology, the DS brains demonstrated a strikingly similar pattern of posterior dominant cortical thinning and subcortical atrophy in the hippocampus, thalamus, and striatum, to that observed in non-DS Alzheimer's disease. Care must be taken to avoid underestimating amyloid-associated morphologic changes in DS due to disproportionate size of some subcortical structures and thickness of the cortex.

No MeSH data available.


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The cortical signature of the Down syndrome brain with amyloid pathology: regional variations in cortical thickness in the PIB-positive group (n = 19), when compared to PIB-negative group (n = 27). The color scale on the right represents the significance of the difference in thickness as −log 10 (p-value) with red-yellow indicating thinner cortex and blue-light blue indicating thicker cortex in the PIB-positive group relative to PIB-negative group. The results are false discovery rate corrected at p < 0.05.
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fig2: The cortical signature of the Down syndrome brain with amyloid pathology: regional variations in cortical thickness in the PIB-positive group (n = 19), when compared to PIB-negative group (n = 27). The color scale on the right represents the significance of the difference in thickness as −log 10 (p-value) with red-yellow indicating thinner cortex and blue-light blue indicating thicker cortex in the PIB-positive group relative to PIB-negative group. The results are false discovery rate corrected at p < 0.05.

Mentions: Vertexwise analysis of cortical thickness in the PIB-positive compared to PIB-negative group revealed large confluent clusters of cortical thinning in parieto-temporo-occipital cortices, posterior cingulate, and precuneus cortices along with some small and scattered changes in prefrontal areas. The extent of cortical thinning was more marked in the right hemisphere. In contrast, there were some small, weakly significant areas of greater thickness in the PIB-positive group in the right subgenual cortex and left precentral gyrus (Fig. 2). Removal of the 3 PIB-positive DS individuals, who were too advanced to complete the CAMCOG, did not alter the reported findings (data not shown). Although PIB-negative group was significantly younger than PIB-positive, matching the groups for age is problematic because, by definition, transition to amyloid positivity is a function of age in people with DS (see Annus et al., 2016). Nonetheless, the age bracket from 39 to 48 years contained an overlap of PIB-positive (n = 9) and PIB-negative (n = 13) participants that were matched for age [t(20) = 1.481, p = 0.154]. Reducing the power by only looking at this subgroup meant that the significance of the changes diminished, however at p (uncorr) < 0.05, a similar atrophy pattern to that seen in the full cohort contrast was evident (Supplementary Fig. 3).


The Down syndrome brain in the presence and absence of fibrillar β -amyloidosis
The cortical signature of the Down syndrome brain with amyloid pathology: regional variations in cortical thickness in the PIB-positive group (n = 19), when compared to PIB-negative group (n = 27). The color scale on the right represents the significance of the difference in thickness as −log 10 (p-value) with red-yellow indicating thinner cortex and blue-light blue indicating thicker cortex in the PIB-positive group relative to PIB-negative group. The results are false discovery rate corrected at p < 0.05.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5391869&req=5

fig2: The cortical signature of the Down syndrome brain with amyloid pathology: regional variations in cortical thickness in the PIB-positive group (n = 19), when compared to PIB-negative group (n = 27). The color scale on the right represents the significance of the difference in thickness as −log 10 (p-value) with red-yellow indicating thinner cortex and blue-light blue indicating thicker cortex in the PIB-positive group relative to PIB-negative group. The results are false discovery rate corrected at p < 0.05.
Mentions: Vertexwise analysis of cortical thickness in the PIB-positive compared to PIB-negative group revealed large confluent clusters of cortical thinning in parieto-temporo-occipital cortices, posterior cingulate, and precuneus cortices along with some small and scattered changes in prefrontal areas. The extent of cortical thinning was more marked in the right hemisphere. In contrast, there were some small, weakly significant areas of greater thickness in the PIB-positive group in the right subgenual cortex and left precentral gyrus (Fig. 2). Removal of the 3 PIB-positive DS individuals, who were too advanced to complete the CAMCOG, did not alter the reported findings (data not shown). Although PIB-negative group was significantly younger than PIB-positive, matching the groups for age is problematic because, by definition, transition to amyloid positivity is a function of age in people with DS (see Annus et al., 2016). Nonetheless, the age bracket from 39 to 48 years contained an overlap of PIB-positive (n = 9) and PIB-negative (n = 13) participants that were matched for age [t(20) = 1.481, p = 0.154]. Reducing the power by only looking at this subgroup meant that the significance of the changes diminished, however at p (uncorr) < 0.05, a similar atrophy pattern to that seen in the full cohort contrast was evident (Supplementary Fig. 3).

View Article: PubMed Central - PubMed

ABSTRACT

People with Down syndrome (DS) have a neurodevelopmentally distinct brain and invariably developed amyloid neuropathology by age 50. This cross-sectional study aimed to provide a detailed account of DS brain morphology and the changes occuring with amyloid neuropathology. Forty-six adults with DS underwent structural and amyloid imaging&mdash;the latter using Pittsburgh compound B (PIB) to stratify the cohort into PIB-positive (n&nbsp;= 19) and PIB-negative (n&nbsp;= 27). Age-matched controls (n&nbsp;= 30) underwent structural imaging. Group differences in deep gray matter volumetry and cortical thickness were studied. PIB-negative people with DS have neurodevelopmentally atypical brain, characterized by disproportionately thicker frontal and occipitoparietal cortex and thinner motor cortex and temporal pole with larger putamina and smaller hippocampi than controls. In the presence of amyloid neuropathology, the DS brains demonstrated a strikingly similar pattern of posterior dominant cortical thinning and subcortical atrophy in the hippocampus, thalamus, and striatum, to that observed in non-DS Alzheimer's disease. Care must be taken to avoid underestimating amyloid-associated morphologic changes in DS due to disproportionate size of some subcortical structures and thickness of the cortex.

No MeSH data available.


Related in: MedlinePlus