Single-value brain activity scores reflect both severity and risk across the Alzheimer's continuum

Joram Soch; Anni Richter; Jasmin M Kizilirmak; Hartmut Schütze; Gabriel Ziegler; Slawek Altenstein; Frederic Brosseron; Peter Dechent; Klaus Fliessbach; Silka Dawn Freiesleben; Wenzel Glanz; Daria Gref; Michael T Heneka; Stefan Hetzer; Enise I Incesoy; Ingo Kilimann; Okka Kimmich; Luca Kleineidam; Elizabeth Kuhn; Christoph Laske; Andrea Lohse; Falk Lüsebrink; Matthias H Munk; Oliver Peters; Lukas Preis; Josef Priller; Alfredo Ramirez; Sandra Roeske; Ayda Rostamzadeh; Nina Roy-Kluth; Klaus Scheffler; Matthias Schmid; Anja Schneider; Annika Spottke; Eike Jakob Spruth; Stefan Teipel; Jens Wiltfang; Frank Jessen; Michael Wagner; Emrah Düzel; Björn H Schott

doi:10.1093/brain/awae149

Single-value brain activity scores reflect both severity and risk across the Alzheimer's continuum

Brain. 2024 May 14:awae149. doi: 10.1093/brain/awae149. Online ahead of print.

Authors

Joram Soch^{1

2

3}, Anni Richter^{4

5

6}, Jasmin M Kizilirmak^{1

7}, Hartmut Schütze^{8

9}, Gabriel Ziegler^{8

9}, Slawek Altenstein^{10

11}, Frederic Brosseron¹², Peter Dechent¹³, Klaus Fliessbach^{12

14}, Silka Dawn Freiesleben^{10

11}, Wenzel Glanz⁸, Daria Gref¹¹, Michael T Heneka¹⁵, Stefan Hetzer¹⁶, Enise I Incesoy^{8

9

17}, Ingo Kilimann^{18

19}, Okka Kimmich¹², Luca Kleineidam^{12

14}, Elizabeth Kuhn¹², Christoph Laske^{20

21}, Andrea Lohse¹¹, Falk Lüsebrink⁸, Matthias H Munk^{20

22}, Oliver Peters^{10

11}, Lukas Preis¹¹, Josef Priller^{10

11

23

24}, Alfredo Ramirez^{12

14

25

26

27}, Sandra Roeske¹², Ayda Rostamzadeh²⁸, Nina Roy-Kluth¹², Klaus Scheffler²⁹, Matthias Schmid^{12

30}, Anja Schneider^{12

14}, Annika Spottke^{12

31}, Eike Jakob Spruth^{10

11}, Stefan Teipel^{18

19}, Jens Wiltfang^{1

32

33}, Frank Jessen^{12

25

28}, Michael Wagner^{12

14}, Emrah Düzel^{8

9}, Björn H Schott^{1

4

32

34}

Affiliations

¹ German Center for Neurodegenerative Diseases (DZNE), 37075 Göttingen, Germany.
² Bernstein Center for Computational Neuroscience (BCCN), 10117 Berlin, Germany.
³ Max Planck Institute for Human Cognitive and Brain Sciences (MPI CBS), Leipzig, Germany.
⁴ Leibniz Institute for Neurobiology (LIN), 39118 Magdeburg, Germany.
⁵ German Center for Mental Health (DZPG), partner site Halle-Jena-Magdeburg, 39120 Magdeburg, Germany.
⁶ Center for Intervention and Research on adaptive and maladaptive brain Circuits underlying mental health (C-I-R-C), Halle-Jena-Magdeburg, 39120 Magdeburg, Germany.
⁷ German Center for Higher Education Research and Science Studies (DZHW), 30159 Hannover, Germany.
⁸ German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany.
⁹ Institute of Cognitive Neurology and Dementia Research (IKND), Otto von Guericke University, 39120 Magdeburg, Germany.
¹⁰ German Center for Neurodegenerative Diseases (DZNE), 10117 Berlin, Germany.
¹¹ Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
¹² German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
¹³ MR-Research in Neurosciences, Department of Cognitive Neurology, Georg August University, 37075 Göttingen, Germany.
¹⁴ Department of Neurodegenerative Disease and Geriatric Psychiatry, University of Bonn Medical Center, Venusberg-Campus 1, 53127 Bonn, Germany.
¹⁵ Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4367 Belvaux, Luxembourg.
¹⁶ Berlin Center for Advanced Neuroimaging, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
¹⁷ Department for Psychiatry and Psychotherapy, University Clinic Magdeburg, 39120 Magdeburg, Germany.
¹⁸ German Center for Neurodegenerative Diseases (DZNE), 18147 Rostock, Germany.
¹⁹ Department of Psychosomatic Medicine, Rostock University Medical Center, 18147 Rostock, Germany.
²⁰ German Center for Neurodegenerative Diseases (DZNE), 72076 Tübingen, Germany.
²¹ Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, 72076 Tübingen, Germany.
²² Department of Psychiatry and Psychotherapy, University of Tübingen, 72076 Tübingen, Germany.
²³ School of Medicine, Department of Psychiatry and Psychotherapy, Technical University of Munich, 81675 Munich, Germany.
²⁴ University of Edinburgh and UK DRI, Edinburgh EH16 4SB, UK.
²⁵ Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Köln, Germany.
²⁶ Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50924 Cologne, Germany.
²⁷ Department of Psychiatry & Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, TX 78229, USA.
²⁸ Department of Psychiatry, University of Cologne, Medical Faculty, 50924 Cologne, Germany.
²⁹ Department for Biomedical Magnetic Resonance, University of Tübingen, 72076 Tübingen, Germany.
³⁰ Institute for Medical Biometry, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
³¹ Department of Neurology, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
³² Department of Psychiatry and Psychotherapy, University Medical Center, 37075 Göttingen, Germany.
³³ Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal.
³⁴ Center for Behavioral Brain Sciences (CBBS), 39106 Magdeburg, Germany.

PMID: 38743817
DOI: 10.1093/brain/awae149

Abstract

Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional magnetic resonance imaging (fMRI) activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive aging. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer's disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD). To this end, we analyzed subsequent memory fMRI data from individuals with SCD, MCI, and AD dementia as well as healthy controls (HC) and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-center DELCODE study (N = 468). Based on the individual participants' whole-brain fMRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity, and ApoE genotype. Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to HC, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aβ-positive and Aβ-negative individuals in SCD and AD-rel, and between ApoE ε4 carriers and non-carriers in AD-rel. Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients.

Keywords: Alzheimer’s disease; dementia risk; fMRI scores; mild cognitive impairment; novelty processing; subsequent memory.