IC‐P‐004: AMYLOID BURDEN AND CORTICAL ATROPHY IN NON‐DEMENTED DOWN SYNDROME

The triplicate copy of amyloid precursor protein gene (APP; chromosome 21) in Down syndrome (DS) genetically predisposes adults with DS to over production of amyloid-β (Aβ) leading to increased Aβ plaque deposition and a higher prevalence of Alzheimer's disease (AD) and dementia. Patterned localization of Aβ plaques are a hallmark of AD. This study investigated the relationship between co-localized Aβ deposition and cortical atrophy in non-demented adults with DS. Sixty-seven non-demented adults with DS (38M, 29F; 37±7yrs) underwent [11C]PiB PET and anatomical T1-weighted MRI. Cortical thickness in six AD-vulnerable ROIs (ie. entorhinal cortex, fusiform gyrus, parahippocampal gyrus, cingulate isthmus, posterior cingulate, and precuneus) was obtained from T1-weighted images using FreeSurfer (6.0.0). Parametric standard uptake value ratio (SUVR) images were generated in native T1 space with cerebellar gray matter as a reference region. Linear regression, adjusted for age, was used to investigate PiB status group (Aβ- vs. Aβ+) differences in cortical thickness as well as investigate the effect of local and global amyloid burden on cortical thickness. No differences in cortical atrophy were observed between the Aβ- and Aβ+ groups (Table 1). Secondary analyses revealed significant (p<.0001) positive correlations between age and global PiB retention, and significant negative correlations (p<.05) between age and cortical thickness in the precuneus, cingulate isthmus, parahippocampal gyrus, and fusiform. Further, regression analyses displayed significant (p <.05) negative correlations between co-localized PiB SUVR and cortical thickness in the precuneus, entorhinal cortex, and fusiform gyrus, and which remained significant in the precuneus and entorhinal cortex when correcting for age (Table 2). Similarly, significant (p <.05) negative correlations were present between global Aβ burden and cortical thickness in the precuneus, cingulate isthmus, posterior cingulate, and fusiform gyrus, with the correlation remaining significant in the precuneus after adjustment for age (Table 3). The robust association between age and amyloid accumulation precludes discrimination of the effects of normative age-related atrophy and Aβ deposition. However, when combined with our previously published longitudinal analysis of this cohort these results suggest that early Aβ aggregation has local and global deleterious effects on brain structure.