NeuroImage: Clinical (Jan 2020)
Multimodal MRI analysis of basal forebrain structure and function across the Alzheimer’s disease spectrum
- Meret Herdick,
- Martin Dyrba,
- Hans-Christian J. Fritz,
- Slawek Altenstein,
- Tommaso Ballarini,
- Frederic Brosseron,
- Katharina Buerger,
- Arda Can Cetindag,
- Peter Dechent,
- Laura Dobisch,
- Emrah Duezel,
- Birgit Ertl-Wagner,
- Klaus Fliessbach,
- Silka Dawn Freiesleben,
- Ingo Frommann,
- Wenzel Glanz,
- John Dylan Haynes,
- Michael T. Heneka,
- Daniel Janowitz,
- Ingo Kilimann,
- Christoph Laske,
- Coraline D. Metzger,
- Matthias H. Munk,
- Oliver Peters,
- Josef Priller,
- Nina Roy,
- Klaus Scheffler,
- Anja Schneider,
- Annika Spottke,
- Eike Jakob Spruth,
- Maike Tscheuschler,
- Ruth Vukovich,
- Jens Wiltfang,
- Frank Jessen,
- Stefan Teipel,
- Michel J. Grothe
Affiliations
- Meret Herdick
- German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
- Martin Dyrba
- German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany
- Hans-Christian J. Fritz
- German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
- Slawek Altenstein
- German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité, Charitéplatz 1, 10117 Berlin, Germany
- Tommaso Ballarini
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Frederic Brosseron
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Katharina Buerger
- German Center for Neurodegenerative Diseases (DZNE, Munich), Feodor-Lynen-Strasse 17, 81377 Munich, Germany; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Feodor-Lynen-Strasse 17, 81377 Munich, Germany
- Arda Can Cetindag
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Psychiatry and Psychotherapy, Hindenburgdamm 30, 12203 Berlin, Germany
- Peter Dechent
- MR-Research in Neurology and Psychiatry, Georg-August-University Göttingen, Germany
- Laura Dobisch
- German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
- Emrah Duezel
- German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
- Birgit Ertl-Wagner
- Institute for Clinical Radiology, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany
- Klaus Fliessbach
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Silka Dawn Freiesleben
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Psychiatry and Psychotherapy, Hindenburgdamm 30, 12203 Berlin, Germany
- Ingo Frommann
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Wenzel Glanz
- German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
- John Dylan Haynes
- Bernstein Center for Computational Neuroscience, Charité — Universitätsmedizin, Berlin, Germany
- Michael T. Heneka
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Daniel Janowitz
- Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Feodor-Lynen-Strasse 17, 81377 Munich, Germany
- Ingo Kilimann
- German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
- Christoph Laske
- German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
- Coraline D. Metzger
- German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany; Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg, Germany
- Matthias H. Munk
- German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
- Oliver Peters
- German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Psychiatry and Psychotherapy, Hindenburgdamm 30, 12203 Berlin, Germany
- Josef Priller
- German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité, Charitéplatz 1, 10117 Berlin, Germany
- Nina Roy
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Klaus Scheffler
- Department for Biomedical Magnetic Resonance, University of Tübingen, 72076 Tübingen, Germany
- Anja Schneider
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Annika Spottke
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Department of Neurology, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
- Eike Jakob Spruth
- German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité, Charitéplatz 1, 10117 Berlin, Germany
- Maike Tscheuschler
- Department of Psychiatry, University of Cologne, Medical Faculty, Kerpener Strasse 62, 50924 Cologne, Germany
- Ruth Vukovich
- Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Von-Siebold-Str. 5, 37075 Goettingen, Germany
- Jens Wiltfang
- Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Von-Siebold-Str. 5, 37075 Goettingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany; Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
- Frank Jessen
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Department of Psychiatry, University of Cologne, Medical Faculty, Kerpener Strasse 62, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931Köln, Germany
- Stefan Teipel
- German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany; Corresponding authors at: DZNE German Center for Neurodegenerative Diseases, Rostock, c/o Zentrum für Nervenheilkunde, Gehlsheimer Str. 20, D-18147 Rostock, Germany.
- Michel J. Grothe
- German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain; Corresponding authors at: DZNE German Center for Neurodegenerative Diseases, Rostock, c/o Zentrum für Nervenheilkunde, Gehlsheimer Str. 20, D-18147 Rostock, Germany.
- Journal volume & issue
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Vol. 28
p. 102495
Abstract
Background: Dysfunction of the cholinergic basal forebrain (cBF) is associated with cognitive decline in Alzheimer’s disease (AD). Multimodal MRI allows for the investigation of cBF changes in-vivo. In this study we assessed alterations in cBF functional connectivity (FC), mean diffusivity (MD), and volume across the spectrum of AD. We further assessed effects of amyloid pathology on these changes. Methods: Participants included healthy controls, and subjects with subjective cognitive decline (SCD), mild cognitive impairment (MCI), or AD dementia (ADD) from the multicenter DELCODE study. Resting-state functional MRI (rs-fMRI) and structural MRI data was available for 477 subjects, and a subset of 243 subjects also had DTI data available. Differences between diagnostic groups were investigated using seed-based FC, volumetric, and MD analyses of functionally defined anterior (a-cBF) and posterior (p-cBF) subdivisions of a cytoarchitectonic cBF region-of-interest. In complementary analyses groups were stratified according to amyloid status based on CSF Aβ42/40 biomarker data, which was available in a subset of participants. Results: a-cBF and p-cBF subdivisions showed regional FC profiles that were highly consistent with previously reported patterns, but there were only minimal differences between diagnostic groups. Compared to controls, cBF volumes and MD were significantly different in MCI and ADD but not in SCD. The Aβ42/40 stratified analyses largely matched these results. Conclusions: We reproduced subregion-specific FC profiles of the cBF in a clinical sample spanning the AD spectrum. At least in this multicentric cohort study, cBF-FC did not show marked changes along the AD spectrum, and multimodal MRI did not provide more sensitive measures of AD-related cBF changes compared to volumetry.
