Cortical Amyloid Burden Relates to Basal Forebrain Volume in Subjective Cognitive Decline

Article type: Research Article

Authors: Daamen, Marcel^{a; *} | Scheef, Lukas^{a; b; c} | Li, Shumei^a | Grothe, Michel J.^d | Gaertner, Florian C.^e | Buchert, Ralph^{f; g} | Buerger, Katharina^{h; i} | Dobisch, Laura^j | Drzezga, Alexander^{a; k; l} | Essler, Markus^e | Ewers, Michael^m | Fliessbach, Klaus^{a; n} | Herrera Melendez, Ana Lucia^o | Hetzer, Stefan^p | Janowitz, Danielⁱ | Kilimann, Ingo^{q; r} | Krause, Bernd Joachim^s | Lange, Catharina^f | Laske, Christoph^{t; u} | Munk, Matthias H.^{t; v} | Peters, Oliver^{o; w} | Priller, Josef^{w; x; y; z} | Ramirez, Alfredo^{a; n; aa; ab; ac} | Reimold, Matthias^ad | Rominger, Axel^{ae; af} | Rostamzadeh, Ayda^ag | Roeske, Sandra^a | Roy, Nina^a | Scheffler, Klaus^ah | Schneider, Anja^{a; n} | Spottke, Annika^{a; ai} | Spruth, Eike Jakob^{w; x} | Teipel, Stefan J.^{q; r} | Wagner, Michael^{a; n} | Düzel, Emrah^{j; aj} | Jessen, Frank^{a; aa; ag} | Boecker, Henning^{a; b} | for the DELCODE Study Group

Affiliations: [a] German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany | [b] Department for Diagnostic and Interventional Radiology, University Hospital Bonn, Bonn, Germany | [c] RheinAhrCampus, University of Applied Sciences Koblenz, Remagen, Germany | [d] 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 | [e] Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany | [f] Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany | [g] Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, 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, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany | [l] Institute of Neuroscience and Medicine (INM-2), Molecular Organization of the Brain, Forschungszentrum Jülich, Jülich, Germany | [m] Institute for Clinical Radiology, Ludwig-Maximilians-University Munich, Munich, Germany | [n] Department of Neurodegenerative Disease and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany | [o] Institute of Psychiatry and Psychotherapy, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany | [p] Berlin Center of Advanced Neuroimaging, Charité –Universitätsmedizin Berlin, Berlin, Germany | [q] German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany | [r] Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany | [s] Department of Nuclear Medicine, Rostock University Medical Centre, Rostock, Germany | [t] German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany | [u] Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany | [v] Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany | [w] German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany | [x] Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany | [y] Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Munich, Germany | [z] University of Edinburgh and UK Dementia Research Institute, Edinburgh, UK | [aa] Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany | [ab] Department of Psychiatry and Psychotherapy, Division of Neurogenetics and Molecular Psychiatry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Medical Faculty, Cologne, Germany | [ac] Department of Psychiatry & Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, San Antonio, TX, USA | [ad] Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard-Karls-University, Tübingen, Germany | [ae] Department of Nuclear Medicine, Ludwig-Maximilian-University Munich, Munich, Germany | [af] Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland | [ag] Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany | [ah] Department for Biomedical Magnetic Resonance, University of Tübingen, Tübingen, Germany | [ai] Department of Neurology, University Hospital Bonn, Bonn, Germany | [aj] Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany

Correspondence: [*] Correspondence to: Dr. Marcel Daamen, Clinical Research/ PET Group, Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE) Bonn, Venusberg-Campus 1/99, Germany. Tel.: +49 228 43302 872; E-mail: [email protected].

Abstract: Background: Atrophy of cholinergic basal forebrain (BF) nuclei is a frequent finding in magnetic resonance imaging (MRI) volumetry studies that examined patients with prodromal or clinical Alzheimer’s disease (AD), but less clear for individuals in earlier stages of the clinical AD continuum. Objective: To examine BF volume reductions in subjective cognitive decline (SCD) participants with AD pathologic changes. Methods: The present study compared MRI-based BF volume measurements in age- and sex-matched samples of N = 24 amyloid-positive and N = 24 amyloid-negative SCD individuals, based on binary visual ratings of Florbetaben positron emission tomography (PET) measurements. Additionally, we assessed associations of BF volume with cortical amyloid burden, based on semiquantitative Centiloid (CL) analyses. Results: Group differences approached significance for BF total volume (p = 0.061) and the Ch4 subregion (p = 0.059) only, showing the expected relative volume reductions for the amyloid-positive subgroup. There were also significant inverse correlations between BF volumes and CL values, which again were most robust for BF total volume and the Ch4 subregion. Conclusions: The results are consistent with the hypothesis that amyloid-positive SCD individuals, which are considered to represent a transitional stage on the clinical AD continuum, already show incipient alterations of BF integrity. The negative association with a continuous measure of cortical amyloid burden also suggests that this may reflect an incremental process. Yet, further research is needed to evaluate whether BF changes already emerge at “grey zone” levels of amyloid accumulation, before amyloidosis is reliably detected by PET visual readings.

Keywords: Acetylcholine, Alzheimer’s disease, amyloid, atrophy, basal forebrain, cognitive decline

DOI: 10.3233/JAD-230141

Journal: Journal of Alzheimer's Disease, vol. 95, no. 3, pp. 1013-1028, 2023