Journal Article

DZNE-2020-07300

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Effective connectivity in the default mode network is distinctively disrupted in Alzheimer's disease-A simultaneous resting-state FDG-PET/fMRI study.

Scherr, M. ; Utz, L. ; Tahmasian, M. ; Pasquini, L. ; Grothe, M. J.DZNE* ; Rauschecker, J. P. ; Grimmer, T. ; Drzezga, A. ; Sorg, C. ; Riedl, V. (Corresponding author)

2021
Wiley-Liss New York, NY

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Please use a persistent id in citations: doi:10.1002/hbm.24517

Abstract: A prominent finding of postmortem and molecular imaging studies on Alzheimer's disease (AD) is the accumulation of neuropathological proteins in brain regions of the default mode network (DMN). Molecular models suggest that the progression of disease proteins depends on the directionality of signaling pathways. At network level, effective connectivity (EC) reflects directionality of signaling pathways. We hypothesized a specific pattern of EC in the DMN of patients with AD, related to cognitive impairment. Metabolic connectivity mapping is a novel measure of EC identifying regions of signaling input based on neuroenergetics. We simultaneously acquired resting-state functional MRI and FDG-PET data from patients with early AD (n = 35) and healthy subjects (n = 18) on an integrated PET/MR scanner. We identified two distinct subnetworks of EC in the DMN of healthy subjects: an anterior part with bidirectional EC between hippocampus and medial prefrontal cortex and a posterior part with predominant input into medial parietal cortex. Patients had reduced input into the medial parietal system and absent input from hippocampus into medial prefrontal cortex (p < 0.05, corrected). In a multiple linear regression with unimodal imaging and EC measures (F4,25 = 5.63, p = 0.002, r2 = 0.47), we found that EC (β = 0.45, p = 0.012) was stronger associated with cognitive deficits in patients than any of the PET and fMRI measures alone. Our approach indicates specific disruptions of EC in the DMN of patients with AD and might be suitable to test molecular theories about downstream and upstream spreading of neuropathology in AD.

Keyword(s): Aged (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Alzheimer Disease: physiopathology (MeSH) ; Cerebral Cortex: diagnostic imaging (MeSH) ; Cerebral Cortex: metabolism (MeSH) ; Cerebral Cortex: physiopathology (MeSH) ; Connectome: methods (MeSH) ; Default Mode Network: diagnostic imaging (MeSH) ; Default Mode Network: metabolism (MeSH) ; Default Mode Network: physiopathology (MeSH) ; Humans (MeSH) ; Magnetic Resonance Imaging: methods (MeSH) ; Multimodal Imaging: methods (MeSH) ; Positron-Emission Tomography: methods (MeSH)

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Contributing Institute(s):

1. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2019

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Database coverage:
; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

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