STRUCTURAL CORRELATES OF ALZHEIMER’S DISEASE AND AGING IN DOWN SYNDROME: AN MRI STUDY

Abstract

Down syndrome (DS) has been proposed as a genetic form of Alzheimer's Disease (AD). However, few studies had assessed the structural correlates of AD and aging in DS. Our objective was to evaluate the brain regions vulnerable to AD and aging in DS and the possible modulating effects of amyloid deposition. Subjects were recruited from the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI), a longitudinal cohort to study AD in DS. 68 subjects underwent a 3 Tesla structural MRI and a lumbar puncture (mean age: 41.32, 34.1% female). DS subjects were classified into a cognitive stable group (cs-DS, N=52) and an AD group (n=16). The AD group was subdivided into prodomal Alzheimer (p-DS, N=10) and AD dementia (d-DS, N=6) subgroups. CSF Aß1–42 levels were measured by ELISA. Subjects were classified as Aß+ or Aß- (cutoff <550pg/ml). Cortical thickness (CTh) and normalized hippocampal volume (HV) were obtained using Freesurfer v5.1. We computed the mean CTh in a well-known AD signature map (Dickerson 2009). We performed group comparissons and correlation analyses. We also performed an interaction analysis between age and CSF Aß1–42 to show the regions with an amyloid by age interaction on CTh. The AD group had extensive regions of cortical atrophy in posterior temporoparietal areas with a relative preservation of frontal areas when compared with s-DS. There was a significant gradient of atrophy in the AD signature and HV across groups (d-DS>p-DS>cs-DS). Aging negatively correlated CTh in cs-DS in regions of the frontal cortex. This correlation was also significant for HV but not for the AD signature. CSF Aß1–42 did not correlate with CTh and there were no differences in the Aß+ vs Aß- comparison in cs-DS. However, we found a significant interaction between CSF Aß1–42 levels and age on brain structure in posterior regions.