1. Alzheimer-Like Pattern of Hypometabolism Emerges with Elevated Amyloid-β Burden in Down Syndrome.
- Author
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Lao PJ, Handen BL, Betthauser TJ, Mihaila I, Hartley SL, Cohen AD, Tudorascu DL, Bulova PD, Lopresti BJ, Tumuluru RV, Murali D, Mathis CA, Barnhart TE, Stone CK, Price JC, Devenny DA, Johnson SC, Klunk WE, and Christian BT
- Subjects
- Adult, Alzheimer Disease metabolism, Alzheimer Disease physiopathology, Down Syndrome metabolism, Down Syndrome physiopathology, Female, Fluorodeoxyglucose F18, Humans, Linear Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Positron-Emission Tomography, Radiopharmaceuticals, United States, Alzheimer Disease complications, Amyloid beta-Peptides metabolism, Down Syndrome complications, Gray Matter diagnostic imaging
- Abstract
Background: The Down syndrome (DS) population is genetically predisposed to amyloid-β protein precursor overproduction and Alzheimer's disease (AD)., Objective: The temporal ordering and spatial association between amyloid-β, glucose metabolism, and gray matter (GM) volume in the DS population can provide insight into those associations in the more common sporadic AD., Methods: Twenty-four adults (13 male, 11 female; 39±7 years) with DS underwent [11C]PiB, [18F]FDG, and volumetric MRI scans. Voxel-wise associations between PiB SUVR, FDG SUVR, and GM volume were investigated, with and without individual adjustments for variables of interest., Results: Positive associations of PiB and age were widespread throughout the neocortex and striatum. Negative associations of FDG and age (frontal, parietal, and temporal cortex) and of GM volume and age (frontal and insular cortex) were observed. PiB and FDG were negatively associated in parietal cortex, after adjustment for GM volume., Conclusions: In adults with DS, early amyloid-β accumulation in the striatum is divergent from sporadic AD; however, despite the early striatal amyloid-β, glucose hypometabolism was confined to the typical AD-associated regions, which occurs similarly in autosomal dominant AD. Importantly, the glucose hypometabolism was not explained solely by increased partial volume effect due to GM volume reductions.
- Published
- 2018
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