Martin Scherr1,2, Lorenzo Pasquini3, Gloria Benson4, Rachel Nuttall5,6,7, Martin Gruber8, Julia Neitzel7,8, Felix Brandl6,8, Christian Sorg2,6,8. 1. Department of Neurology, Paracelsus Medical University Salzburg, and Christian Doppler Medical Centre, Salzburg, Austria; Centre for Cognitive Neurosciences Salzburg, Salzburg, Austria. 2. Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, Munich, Germany. 3. Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA. 4. Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany. 5. Department of Psychology, University of Salzburg, Salzburg, Austria. 6. TUM Neuroimaging Center (TUM-NIC), Klinikum rechts der Isar, Technische Universität München, Munich, Germany. 7. General and Experimental Psychology, Department of Psychology, Ludwig-Maximilians-Universität München, Munich, Germany. 8. Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
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.
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.
Authors: Martin Scherr; Lukas Utz; Masoud Tahmasian; Lorenzo Pasquini; Michel J Grothe; Josef P Rauschecker; Timo Grimmer; Alexander Drzezga; Christian Sorg; Valentin Riedl Journal: Hum Brain Mapp Date: 2019-01-30 Impact factor: 5.038
Authors: Christian Sorg; Masoud Tahmasian; Somayeh Maleki Balajoo; Farzaneh Rahmani; Reza Khosrowabadi; Chun Meng; Simon B Eickhoff; Timo Grimmer; Mojtaba Zarei; Alexander Drzezga Journal: Eur J Nucl Med Mol Imaging Date: 2022-02-24 Impact factor: 10.057