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. 2020 Apr 17;12(1):e12013.
doi: 10.1002/dad2.12013. eCollection 2020.

Down syndrome: Distribution of brain amyloid in mild cognitive impairment

David B Keator  1 , Michael J Phelan  2 , Lisa Taylor  1 , Eric Doran  3 , Sharon Krinsky-McHale  4 , Julie Price  5 , Erin E Ballard  1 , William C Kreisl  6 , Christy Hom  1 , Dana Nguyen  1 , Margaret Pulsifer  5 , Florence Lai  5 , Diana H Rosas  5 , Adam M Brickman  7 , Nicole Schupf  7 , Michael A Yassa  1   8 , Wayne Silverman  3 , Ira T Lott  3
Affiliations
Free PMC article

Down syndrome: Distribution of brain amyloid in mild cognitive impairment

David B Keator et al. Alzheimers Dement (Amst). .
Free PMC article

Abstract

Introduction: Down syndrome (DS) is associated with a higher risk of dementia. We hypothesize that amyloid beta (Aβ) in specific brain regions differentiates mild cognitive impairment in DS (MCI-DS) and test these hypotheses using cross-sectional and longitudinal data.

Methods: 18F-AV-45 (florbetapir) positron emission tomography (PET) data were collected to analyze amyloid burden in 58 participants clinically classified as cognitively stable (CS) or MCI-DS and 12 longitudinal CS participants.

Results: The study confirmed our hypotheses of increased amyloid in inferior parietal, lateral occipital, and superior frontal regions as the main effects differentiating MCI-DS from the CS groups. The largest annualized amyloid increases in longitudinal CS data were in the rostral middle frontal, superior frontal, superior/middle temporal, and posterior cingulate cortices.

Discussion: This study helps us to understand amyloid in the MCI-DS transitional state between cognitively stable aging and frank dementia in DS. The spatial distribution of Aβ may be a reliable indicator of MCI-DS in DS.

Keywords: ABC‐DS; ADDS; AV‐45; Alzheimer's disease; Down syndrome; MCI; PET; amyloid; dementia.

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Conflict of interest statement

The Co‐Principal Investigators of the ADDS component of the ABC‐DS program are Nicole Schupf, PhD, Doctor of Public Health (DrPh) (Columbia University), Ira Lott, MD, and Wayne Silverman, PhD (UC Irvine). Co‐Principal Investigators of the NiAD ABC‐DS component are Benjamin Handen, PhD and William Klunk, MD, PhD (University of Pittsburgh), and Bradley Christian, PhD (University of Wisconsin‐Madison)

Figures

FIGURE 1
FIGURE 1
Plots showing distributions of unadjusted marginal estimates for each region by diagnosis (left) and the adjusted data (right) after removing the linear associations with age, sex, acquisition site, and region of interest (ROI) volume, scaled to the mean/standard deviation of the CS group
FIGURE 2
FIGURE 2
Voxel‐based contrasts of the MCI‐DS versus CS groups showing effect sizes of increased amyloid load in MCI‐DS compared to CS. Areas of increase corresponding to a priori hypothesized regions are labeled with abbreviations: IPL = inferior parietal lobe; ITG = inferior temporal gyrus; LOC = lateral occipital cortex; LOF = lateral orbitofrontal; MTG = middle temporal gyrus; RMFG = rostral middle frontal gyrus; PCC = posterior cingulate cortex; SFG = superior frontal gyrus; STG = superior temporal gyrus
FIGURE 3
FIGURE 3
Distribution of standardized uptake value ratios (SUVRs) (T1/T0) by region of interest (ROI). Regions are ordered, smallest to largest, with respect to the median ratio. Bracket values mark the 10th and 90th percentiles of the sample, giving a near complete representation of the distribution of values. Values are plotted with a color scale based on the interval between scans. Red circles represent the median value
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