Brain-predicted age in Down syndrome is associated with beta amyloid deposition and cognitive decline

James H Cole,Tiina Annus,Liam R Wilson,Ridhaa Remtulla,Young T Hong,Tim D Fryer,Julio Acosta-Cabronero,Arturo Cardenas-Blanco,Robert Smith,David K Menon,Shahid H Zaman,Peter J Nestor,Anthony J Holland

doi:10.1016/j.neurobiolaging.2017.04.006

Abstract

Individuals with Down syndrome (DS) are more likely to experience earlier onset of multiple facets of physiological aging. This includes brain atrophy, beta amyloid deposition, cognitive decline, and Alzheimer's disease—factors indicative of brain aging. Here, we employed a machine learning approach, using structural neuroimaging data to predict age (i.e., brain-predicted age) in people with DS (N = 46) and typically developing controls (N = 30). Chronological age was then subtracted from brain-predicted age to generate a brain-predicted age difference (brain-PAD) score. DS participants also underwent [11C]-PiB positron emission tomography (PET) scans to index the levels of cerebral beta amyloid deposition, and cognitive assessment. Mean brain-PAD in DS participants' was +2.49 years, significantly greater than controls (p < 0.001). The variability in brain-PAD was associated with the presence and the magnitude of PiB-binding and levels of cognitive performance. Our study indicates that DS is associated with premature structural brain aging, and that age-related alterations in brain structure are associated with individual differences in the rate of beta amyloid deposition and cognitive impairment.

Highlights

Down syndrome (DS), the result of trisomy 21, results in intellectual disability and a set of characteristic physiological and behavioral traits
We considered whether levels of beta amyloid deposition, cognitive decline, and the manifestation of dementia relate to the levels of “age-like” changes to brain structure in DS
DS participants were trending toward being younger (Table 1, p 1⁄4 0.08), while the ratio of males to females was similar between groups (p 1⁄4 0.96)

Summary

Introduction

Down syndrome (DS), the result of trisomy 21, results in intellectual disability and a set of characteristic physiological and behavioral traits. Postmortem and in vivo studies show increased cerebral beta amyloid deposition, neurofibrillary tau tangles, brain atrophy, and white matter lesions in DS (Annus et al, 2016; Head et al, 2016; Lao et al, 2016; Mann and Esiri, 1989; Nelson et al, 2011; Roth et al, 1996; Wisniewski et al, 1985) All these changes have been associated with the typically aging brain, albeit at an older age (Braskie et al, 2010; Fjell et al, 2009; Jack et al, 2014; Rodrigue et al, 2012; Wardlaw et al, 2013).

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