title: Disrupted Intrinsic Networks Link Amyloid-β Pathology and Impaired Cognition in Prodromal Alzheimer's Disease.
abstract: Amyloid-β pathology (Aβ) and impaired cognition characterize Alzheimer's disease (AD); however, neural mechanisms that link Aβ-pathology with impaired cognition are incompletely understood. Large-scale intrinsic connectivity networks (ICNs) are potential candidates for this link: Aβ-pathology affects specific networks in early AD, these networks show disrupted connectivity, and they process specific cognitive functions impaired in AD, like memory or attention. We hypothesized that, in AD, regional changes of ICNs, which persist across rest- and cognitive task-states, might link Aβ-pathology with impaired cognition via impaired intrinsic connectivity. Pittsburgh compound B (PiB)-positron emission tomography reflecting in vivo Aβ-pathology, resting-state fMRI, task-fMRI, and cognitive testing were used in patients with prodromal AD and healthy controls. In patients, default mode network's (DMN) functional connectivity (FC) was reduced in the medial parietal cortex during rest relative to healthy controls, relatively increased in the same region during an attention-demanding task, and associated with patients' cognitive impairment. Local PiB-uptake correlated negatively with DMN connectivity. Importantly, corresponding results were found for the right lateral parietal region of an attentional network. Finally, structural equation modeling confirmed a direct influence of DMN resting-state FC on the association between Aβ-pathology and cognitive impairment. Data provide evidence that disrupted intrinsic network connectivity links Aβ-pathology with cognitive impairment in early AD.
authors.affiliation: Department of Neuroradiology TUM-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München (TUM), 81675 Munich, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Koch
authors.affiliation: Department of Neuroradiology TUM-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München (TUM), 81675 Munich, Germany Department of Experimental Psychology, Oxford University, Oxford OX1 3UD, UK.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Myers
authors.affiliation: Department of Neuroradiology TUM-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München (TUM), 81675 Munich, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Göttler
authors.affiliation: Department of Neuroradiology TUM-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München (TUM), 81675 Munich, Germany.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pasquini
authors.affiliation: Department of Psychiatry.
authors.forename: Timo
authors.initials: T
authors.lastname: Grimmer
authors.affiliation: Department of Nuclear Medicine TUM-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München (TUM), 81675 Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Förster
authors.affiliation: Department of Neuroradiology Department of Psychiatry TUM-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München (TUM), 81675 Munich, Germany.
authors.forename: Andrei
authors.initials: A
authors.lastname: Manoliu
authors.affiliation: Department of Neuroradiology TUM-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München (TUM), 81675 Munich, Germany Graduate School of Systemic Neurosciences (GSN), Ludwig-Maximilians-Universität, Biocenter, 82152 Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Neitzel
authors.affiliation: Department of Psychiatry.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurz
authors.affiliation: Department of Psychiatry.
authors.forename: Hans
authors.initials: H
authors.lastname: Förstl
authors.affiliation: Department of Neuroradiology Department of Nuclear Medicine TUM-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München (TUM), 81675 Munich, Germany.
authors.forename: Valentin
authors.initials: V
authors.lastname: Riedl
authors.affiliation: Department of Neuroradiology Department of Neurology TUM-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München (TUM), 81675 Munich, Germany.
authors.forename: Afra M
authors.initials: AM
authors.lastname: Wohlschläger
authors.affiliation: Klinik und Poliklinik für Nuklearmedizin,50937 Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
authors.affiliation: Department of Neuroradiology Department of Psychiatry Department of Nuclear Medicine TUM-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München (TUM), 81675 Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sorg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001288:Attention / Q000502:physiology; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000378:metabolism* / Q000523:psychology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D013844:Thiazoles
keywords: PiB-PET; amyloid plaques; impaired cognition; intrinsic connectivity networks; prodromal Alzheimer's disease; resting-state fMRI; task-fMRI