In:
Brain Communications, Oxford University Press (OUP)
Abstract:
Approximately 5% of Alzheimer’s Disease patients develop symptoms before age 65 (EOAD), with either sporadic (sEOAD) or dominantly inherited (DIAD) presentations. Both sEOAD and DIAD are characterized by brain amyloid-beta accumulation, tau tangles, hypometabolism and neurodegeneration, but differences in topography and magnitude of these pathological changes are not fully elucidated. In this study, we directly compared patterns of amyloid-beta plaque deposition and glucose hypometabolism in sEOAD and DIAD individuals. Our analysis included 134 symptomatic sEOAD Amyloid-PET positive cases from the University of California, San Francisco, Alzheimer’s Disease Research Center (mean ± standard deviation age 59.7 ± 5.6 years), 89 symptomatic DIAD cases (age 45.8 ± 9.3 years) and 102 cognitively unimpaired non-mutation carriers from the Dominantly Inherited Alzheimer Network study (age 44.9 ± 9.2). Each group underwent clinical and cognitive examinations, 11C-labeled Pittsburgh compound B-PET (PIB-PET) and structural Magnetic Resonance Imaging. 18F-fluorodeoxyglucose-PET (FDG-PET) was also available for most participants. PET scans from both studies were uniformly processed to obtain Standardized Uptake Value Ratio (SUVR, PIB50-70 cerebellar gray reference, FDG30-60 pons reference) images. Statistical analyses included pairwise global and voxelwise group comparisons and group-independent component analyses. Analyses were performed also adjusting for covariates including age, sex, Mini-Mental State Examination, Apolipoprotein-ε4 status, and average composite cortical of Standardized Uptake Value Ratio. Compared to DIAD, sEOAD participants were older at age of onset (mean ± standard deviation, 54.8 ± 8.2 vs. 41.9 ± 8.2, Cohen’s d = 1.91), with more years of education (16.4 ± 2.8 vs. 13.5 ± 3.2, d = 1) and more likely to be Apolipoprotein-ε4 carriers (54.6% ε4 vs. 28.1%, Cramer’s V = 0.26), but similar Mini-Mental State Examination (20.6 ± 6.1 vs. 21.2 ± 7.4, d = 0.08). sEOAD had higher global cortical PIB-PET binding (mean ± standard deviation SUVR, 1.92 ± 0.29 vs. 1.58 ± 0.44, d = 0.96) and greater global cortical FDG-PET hypometabolism (mean ± standard deviation SUVR, 1.32 ± 0.1 vs. 1.39 ± 0.19, d = 0.48) compared to DIAD. Fully adjusted comparisons demonstrated relatively higher PIB-PET SUVR in the medial occipital, thalami, basal ganglia and medial/dorsal frontal regions in DIAD vs. sEOAD. sEOAD showed relatively greater FDG-PET hypometabolism in Alzheimer’s Disease signature temporoparietal regions and caudate nuclei, whereas DIAD showed relatively greater hypometabolism in frontal white matter and pericentral regions. Independent component analyses largely replicated these findings by highlighting common and unique PIB-PET and FDG-PET binding patterns. In summary, our findings suggest both common and distinct patterns of amyloid and glucose hypometabolismin in sporadic and dominantly inherited EOAD.
Type of Medium:
Online Resource
ISSN:
2632-1297
DOI:
10.1093/braincomms/fcae159
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2024
detail.hit.zdb_id:
3020013-1
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