RT Journal Article
SR Electronic
T1 Amyloid accumulation, glucose hypometabolism, and gray matter atrophy in Down syndrome
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 557
OP 557
VO 58
IS supplement 1
A1 Lao, Patrick
A1 Handen, Ben
A1 Betthauser, Tobey
A1 Price, Julie
A1 Klunk, William
A1 Bulova, Peter
A1 Hartley, Sigan
A1 Hardison, Reginah
A1 Tumuluru, Rameshwari
A1 Murali, Dhanabalan
A1 Mathis, Chester
A1 Cohen, Annie
A1 Barnhart, Todd
A1 Tudorascu, Dana
A1 Devenny, Darlynne
A1 Johnson, Sterling
A1 Christian, Bradley
YR 2017
UL http://jnm.snmjournals.org/content/58/supplement_1/557.abstract
AB 557Objectives: Amyloid-β plaques, cerebral hypometabolism, and gray matter (GM) atrophy are common biomarkers for Alzheimer’s disease (AD) pathology. The aim of this work was to use functional and structural imaging to provide insight into the association between these AD biomarkers in the Down syndrome (DS) population, which is genetically predisposed to early amyloid-β accumulation and AD.Methods: Twenty-three non-demented adults (12M,11F; 38.6±7.0yrs) with DS underwent [11C]PiB scan and a subsequent [18F]FDG scan (124.7±102.6 days after), as well as T1 and T2 MRIs at each visit. Parametric standard uptake value ratios (SUVRs) were calculated for PiB (50-70 min) and FDG (40-60 min) using cerebellar gray matter as the reference region. Parametric GM volume images were estimated from a multispectral tissue-type segmentation (Matlab2015, SPM12). Parametric images were spatially normalized using a study-specific PET template and analyzed in MNI space. Biological parametric mapping (BPM; MATLAB2011a, SPM5) was used to investigate associations between PiB and FDG SUVR images, as well as GM volume images. Common covariates, including age, sex, cognitive function, and APOE4 allele, were investigated in SPM12 (cluster size >1000 voxels, αuncorrected=0.001).Results: PiB and FDG SUVR were negatively associated in the precuneus and left parietal cortex, while PiB or FDG SUVR were not associated with GM volume. BPM results did not survive correction for age, but survived separate correction for sex, cognitive function, and APOE4 in this non-demented cohort of adults with DS. SPM analysis showed a positive association between PiB SUVR and age in the anterior cingulate, frontal cortex, parietal cortex, precuneus, striatum, and temporal cortex. FDG SUVR was negatively associated with age in the precuneus, right parietal and temporal cortex, and right thalamus. GM was negatively associated with age in the frontal cortex.Conclusion: Imaging in the non-demented DS population demonstrates AD-like neuropathology, such as early amyloid accumulation and glucose hypometabolism. While, the amyloid accumulation and glucose hypometabolism were correlated in regions consistent with AD, the GM atrophy occurred in frontal cortex, which is typically spared until later in the AD process. Therefore, the GM atrophy beginning in the frontal cortex may reflect the DS phenotype. Research Support: R01 AG031110, U54 HD090256, U01 AG051406