Decoupling of Local Metabolic Activity and Functional Connectivity Links to Amyloid in Alzheimer's Disease

作者：Scherr Martin; Pasquini Lorenzo; Benson Gloria; Nuttall Rachel; Gruber Martin; Neitzel Julia; Brandl Felix; Sorg Christian

来源：Journal of Alzheimer's Disease, 2018, 64(2): 405-415.

DOI：10.3233/JAD-180022

• Alzheimer's disease
• amyloid-beta
• default mode network
• functional connectivity
• local metabolic activity

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.

• 出版日期2018