Spatially Distributed Amyloid-β Reduces Glucose Metabolism in Mild Cognitive Impairment
| Autor: | Alex P. Zijdenbos, Felix Carbonell, Barry J. Bedell |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty positron emission tomography Amyloid β Genotype glucose metabolism Apolipoprotein E4 Carbohydrate metabolism amyloid-β Older population 03 medical and health sciences 0302 clinical medicine Neuroimaging Fluorodeoxyglucose F18 Internal medicine medicine Humans Cognitive Dysfunction Cognitive impairment Aged Aged 80 and over Cerebral Cortex Amyloid beta-Peptides medicine.diagnostic_test business.industry General Neuroscience singular value decomposition General Medicine cross-correlation Aβ deposition Magnetic Resonance Imaging Psychiatry and Mental health Clinical Psychology 030104 developmental biology Endocrinology Glucose Positron emission tomography Positron-Emission Tomography Female Geriatrics and Gerontology business Alzheimer’s disease 030217 neurology & neurosurgery Alzheimer's Disease Neuroimaging Initiative Research Article |
| Zdroj: | Journal of Alzheimer's Disease |
| ISSN: | 1875-8908 |
| Popis: | Background: Several positron emission tomography (PET) studies have explored the relationship between amyloid-β (Aβ), glucose metabolism, and the APOE ɛ4 genotype. It has been reported that APOE ɛ4, and not aggregated Aβ, contributes to glucose hypometabolism in pre-clinical stages of Alzheimer’s disease (AD) pathology. Objective: We hypothesize that typical measurements of Aβ taken either from composite regions-of-interest with relatively high burden actually cover significant patterns of the relationship with glucose metabolism. In contrast, spatially weighted measures of Aβ are more related to glucose metabolism in cognitively normal (CN) aging and mild cognitive impairment (MCI). Methods: We have generated a score of amyloid burden based on a joint singular value decomposition (SVD) of the cross-correlation structure between glucose metabolism, as measured by [18F]2-fluoro-2-deoxyglucose (FDG) PET, and Aβ, as measured by [18F]florbetapir PET, from the Alzheimer’s Disease Neuroimaging Initiative study. This SVD-based score reveals cortical regions where a reduced glucose metabolism is maximally correlated with distributed patterns of Aβ. Results: From an older population of CN and MCI subjects, we found that the SVD-based Aβ score was significantly correlated with glucose metabolism in several cortical regions. Additionally, the corresponding Aβ network has hubs that contribute to distributed glucose hypometabolism, which, in turn, are not necessarily foci of Aβ deposition. Conclusions: Our approach uncovered hidden patterns of the glucose metabolism-Aβ relationship. We showed that the SVD-based Aβ score produces a stronger relationship with decreasing glucose metabolism than either APOE ɛ4 genotype or global measures of Aβ burden. |
| Databáze: | OpenAIRE |
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