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

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

doi:10.3233/JAD-180022

Klinik und Poliklinik für Psychiatrie und Psychotherapie (Prof. Priller)

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Document type:: Journal Article
Author(s):: Scherr, Martin; Pasquini, Lorenzo; Benson, Gloria; Nuttall, Rachel; Gruber, Martin; Neitzel, Julia; Brandl, Felix; Sorg, Christian
Title:: Decoupling of Local Metabolic Activity and Functional Connectivity Links to Amyloid in Alzheimer's Disease.
Abstract:: 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.We hypothesized progressive decoupling between LMA and FC in AD, which is linked to amyloid-? pathology (A?).Healthy adults (n=20) and A?+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? of the pDMN. Coupling between LMA and FC (rLA/FC) was estimated by voxelwise correlation.RLMA/FC decreased with disease severity (F=20.09, p<0.001). This decrease was specifically associated with pDMN A? (r=-0.273, p=0.029) but not global A? (r=-0.112, p=0.378) and with the impact of A? on FC (i.e., rA?/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 A?, pDMN A?, pDMN LMA, and pDMN FC, respectively.Results demonstrate increasing decoupling of LMA from its FC in AD. Data suggest that decoupling is driven by local A? and contributes to memory decline.
Journal title abbreviation:: J Alzheimers Dis
Year:: 2018
Journal volume:: 64
Journal issue:: 2
Pages contribution:: 405-415
Language:: eng
Fulltext / DOI:: doi:10.3233/JAD-180022
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/29843243
Print-ISSN:: 1387-2877
TUM Institution:: Fachgebiet Neuroradiologie (Prof. Zimmer); Klinik und Poliklinik für Psychiatrie und Psychotherapie
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