Authors: Scherr, Martin | Pasquini, Lorenzo | Benson, Gloria | Nuttall, Rachel | Gruber, Martin | Neitzel, Julia | Brandl, Felix | Sorg, Christian | for the Alzheimer’s Disease Neuroimaging Initiative
Article Type:
Research Article
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-β pathology (Aβ). Methods: Healthy adults (n =20) and Aβ+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 Aβ of the pDMN. Coupling between LMA and FC (rLA/FC ) was estimated by voxelwise correlation. Results: RLMA/FC decreased with disease severity (F =20.09, p <0.001). This decrease was specifically associated with pDMN Aβ (r =−0.273, p =0.029) but not global Aβ (r =−0.112, p =0.378) and with the impact of Aβ on FC (i.e., rAβ/FC, r =−0.339; p =0.006). In multiple regression models rLMA/FC was also associated with memory impairment, reduced cognitive speed and flexibility, outperforming global Aβ, pDMN Aβ, 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 Aβ and contributes to memory decline.
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Keywords: Alzheimer’s disease, amyloid-β, default mode network, functional connectivity, local metabolic activity
DOI: 10.3233/JAD-180022
Citation: Journal of Alzheimer's Disease,
vol. 64, no. 2, pp. 405-415, 2018
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