Abstract
Background: Both ongoing local metabolic activity (LMA) and corresponding functional connectivity (FC) with remote brain regions are progressively impaired in Alzheimer's disease (AD), particularly in the posterior default mode network (pDMN);however, it is unknown how these impairments interact. It is well known that decreasing mean synaptic activity of a region, i.e., decreasing LMA, reduces the region's sensitivity to afferent input from other regions, i.e., FC. Objective: We hypothesized progressive decoupling between LMA and FC in AD, which is linked to amyloid-beta pathology (A beta). Methods: Healthy adults (n = 20) and A beta+patients without memory impairment (n = 9), early MCI (n = 21), late MCI (n = 18) and AD(n = 22) were assessed by resting-state fMRI, FDG-PET, and AV-45-PET to measure FC, LMA, and A beta of the pDMN. Coupling between LMA and FC (r(LA/FC)) was estimated by voxelwise correlation. Results: R-LMA/FC decreased with disease severity (F = 20.09, p < 0.001). This decreasewas specifically associated with pDMN A beta (r = -0.273, p = 0.029) but not global A beta (r = -0.112, p = 0.378) and with the impact of A beta on FC (i.e., r(A beta/FC), r = -0.339;p = 0.006). In multiple regression models r(LMA/FC) was also associated with memory impairment, reduced cognitive speed and flexibility, outperforming global A beta, pDMN A beta, pDMN LMA, and pDMN FC, respectively. Conclusion: Results demonstrate increasing decoupling of LMA from its FC in AD. Data suggest that decoupling is driven by local A beta and contributes to memory decline.
| Item Type: | Journal article |
|---|---|
| Faculties: | Psychology and Education Science > Department Psychology |
| Subjects: | 100 Philosophy and Psychology > 150 Psychology |
| ISSN: | 1387-2877 |
| Language: | English |
| Item ID: | 66114 |
| Date Deposited: | 19. Jul 2019 12:19 |
| Last Modified: | 04. Nov 2020 13:46 |
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