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Scherr, Martin; Pasquini, Lorenzo; Benson, Gloria; Nuttall, Rachel; Gruber, Martin; Neitzel, Julia; Brandl, Felix; Sorg, Christian (2018): Decoupling of Local Metabolic Activity and Functional Connectivity Links to Amyloid in Alzheimer's Disease. In: Journal of Alzheimers Disease, Vol. 64, No. 2: pp. 405-415
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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.