Abnormal Regional and Global Connectivity Measures in Subjective Cognitive Decline Depending on Cerebral Amyloid Status

Article type: Research Article

Authors: Li, Shumei^{a; 1} | Daamen, Marcel^{a; 1} | Scheef, Lukas^{a; b} | Gaertner, Florian C.^c | Buchert, Ralph^{d; e} | Buchmann, Martina^{f; g} | Buerger, Katharina^{h; i} | Catak, Cihanⁱ | Dobisch, Laura^j | Drzezga, Alexander^k | Ertl-Wagner, Birgit^{l; m} | Essler, Markus^c | Fliessbach, Klaus^{a; o} | Haynes, John Dylan^p | Incesoy, Enise Irem^{q; r} | Kilimann, Ingo^{s; t} | Krause, Bernd J.^u | Lange, Catharina^d | Laske, Christoph^{f; g} | Priller, Josef^{q; v} | Ramirez, Alfredo^{o; w} | Reimold, Matthias^x | Rominger, Axel^{y; z} | Roy, Nina^a | Scheffler, Klaus^aa | Maurer, Angelika^{a; b} | Schneider, Anja^{a; o} | Spottke, Annika^{a; ab} | Spruth, Eike Jakob^{q; v} | Teipel, Stefan J.^{s; t} | Tscheuschler, Maike^ac | Wagner, Michael^{a; o} | Wolfsgruber, Steffen^{a; o} | Düzel, Emrah^{j; ad} | Jessen, Frank^{a; ac; ae} | Peters, Oliver^{q; r} | Boecker, Henning^{a; b; *} | the DELCODE Study Group

Affiliations: [a] German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany | [b] Department of Radiology, University Hospital Bonn, Bonn, Germany | [c] Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany | [d] Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany | [e] Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany | [f] German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany | [g] Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany | [h] German Center for Neurodegenerative Diseases (DZNE), Munich, Germany | [i] Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilian University Munich, Munich, Germany | [j] German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany | [k] Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany | [l] Institute for Clinical Radiology, Ludwig-Maximilian University Munich, Munich, Germany | [m] Department of Medical Imaging, University of Toronto, Toronto, Canada | [o] Department of Neurodegeneration and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany | [p] Bernstein Center for Computational Neuroscience, Charité - Universitätsmedizin, Berlin, Germany | [q] German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany | [r] Charité –Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Psychiatry and Psychotherapy, Berlin, Germany | [s] German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald | [t] Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany | [u] Department of Nuclear Medicine, Rostock University Medical Centre, Rostock, Germany | [v] Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin, Berlin, Germany | [w] Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany | [x] Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard-Karls-University Tuebingen, Tuebingen, Germany | [y] Department of Nuclear Medicine, University Hospital, Ludwig-Maximilian University Munich, Munich, Germany | [z] Department of Nuclear Medicine, Bern University Hospital, Bern, Switzerland | [aa] Department for Biomedical Magnetic Resonance, University of Tuebingen, Tuebingen, Germany | [ab] Department of Neurology, University Hospital Bonn, Bonn, Germany | [ac] Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany | [ad] Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany | [ae] Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany

Correspondence: [*] Correspondence to: Prof. Henning Boecker, Functional Neuroimaging Group, Department of Radiology, University Hospital Bonn, Venusberg-Campus 1 - Building 07, D-53127 Bonn, Germany.Tel.: +49 228 287 15980; Fax: +49 228 287 14457; E-mail: henning.boecker@ukbonn.de.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Amyloid-β accumulation was found to alter precuneus-based functional connectivity (FC) in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia, but its impact is less clear in subjective cognitive decline (SCD), which in combination with AD pathologic change is theorized to correspond to stage 2 of the Alzheimer’s continuum in the 2018 NIA-AA research framework. Objective:This study addresses how amyloid pathology relates to resting-state fMRI FC in SCD, especially focusing on the precuneus. Methods:From the DELCODE cohort, two groups of 24 age- and gender-matched amyloid-positive (SCDAβ+) and amyloidnegative SCD (SCDβ−) patients were selected according to visual [18F]-Florbetaben (FBB) PET readings, and studied with resting-state fMRI. Local (regional homogeneity [ReHo], fractional amplitude of low-frequency fluctuations [fALFF]) and global (degree centrality [DC], precuneus seed-based FC) measures were compared between groups. Follow-up correlation analyses probed relationships of group differences with global and precuneal amyloid load, as measured by FBB standard uptake value ratios (SUVR=⫖FBB). Results:ReHo was significantly higher (voxel-wise p < 0.01, cluster-level p < 0.05) in the bilateral precuneus for SCDAβ+patients, whereas fALFF was not altered between groups. Relatively higher precuneus-based FC with occipital areas (but no altered DC) was observed in SCDAβ+ patients. In this latter cluster, precuneus-occipital FC correlated positively with global (SCDAβ+) and precuneus SUVRFBB (both groups). Conclusion:While partial confounding influences due to a higher APOE ε4 carrier ratio among SCDAβ+ patients cannot be excluded, exploratory results indicate functional alterations in the precuneus hub region that were related to amyloid-β load, highlighting incipient pathology in stage 2 of the AD continuum.

Keywords: Alzheimer’s disease, amyloid, functional magnetic resonance imaging, occipital cortex, PET, precuneus, prodromal symptoms, subjective cognitive decline

DOI: 10.3233/JAD-200472

Journal: Journal of Alzheimer's Disease, vol. 79, no. 2, pp. 493-509, 2021