Altered limbic functional connectivity in individuals with subjective cognitive decline: Converging and diverging findings across Chinese and German cohorts

Xueyan Jiang; Xiaochen Hu; Marcel Daamen; Xiaoqi Wang; Chunqiu Fan; Dix Meiberth; Annika Spottke; Sandra Roeske; Klaus Fliessbach; Eike Jakob Spruth; Slawek Altenstein; Andrea Lohse; Niels Hansen; Wenzel Glanz; Enise I Incesoy; Laura Dobisch; Daniel Janowitz; Boris-Stephan Rauchmann; Alfredo Ramirez; Ingo Kilimann; Matthias H Munk; Xiao Wang; Luisa-Sophie Schneider; Tatjana Gabelin; Nina Roy; Steffen Wolfsgruber; Luca Kleineidam; Stefan Hetzer; Peter Dechent; Michael Ewers; Klaus Scheffler; Holger Amthauer; Ralph Buchert; Markus Essler; Alexander Drzezga; Axel Rominger; Bernd J Krause; Matthias Reimold; Josef Priller; Anja Schneider; Jens Wiltfang; Katharina Buerger; Robert Perneczky; Stefan Teipel; Christoph Laske; Oliver Peters; Emrah Düzel; Michael Wagner; Jiehui Jiang; Frank Jessen; Henning Boecker; Ying Han

doi:10.1002/alz.13068

Altered limbic functional connectivity in individuals with subjective cognitive decline: Converging and diverging findings across Chinese and German cohorts

Alzheimers Dement. 2023 Nov;19(11):4922-4934. doi: 10.1002/alz.13068. Epub 2023 Apr 18.

Authors

Xueyan Jiang^{1

2

3}, Xiaochen Hu⁴, Marcel Daamen², Xiaoqi Wang¹, Chunqiu Fan¹, Dix Meiberth^{2

4}, Annika Spottke^{2

5}, Sandra Roeske², Klaus Fliessbach^{2

6}, Eike Jakob Spruth^{7

8}, Slawek Altenstein^{7

8}, Andrea Lohse⁸, Niels Hansen⁹, Wenzel Glanz¹⁰, Enise I Incesoy^{10

11

12}, Laura Dobisch¹⁰, Daniel Janowitz¹³, Boris-Stephan Rauchmann¹⁴, Alfredo Ramirez^{2

6

15

16

17}, Ingo Kilimann^{18

19}, Matthias H Munk^{20

21}, Xiao Wang²², Luisa-Sophie Schneider²², Tatjana Gabelin²², Nina Roy², Steffen Wolfsgruber^{2

6}, Luca Kleineidam^{2

6}, Stefan Hetzer²³, Peter Dechent²⁴, Michael Ewers²⁵, Klaus Scheffler²⁶, Holger Amthauer²⁷, Ralph Buchert^{27

28}, Markus Essler²⁹, Alexander Drzezga^{2

30

31}, Axel Rominger^{32

33}, Bernd J Krause³⁴, Matthias Reimold³⁵, Josef Priller^{7

8

36

37}, Anja Schneider^{2

6}, Jens Wiltfang^{9

38

39}, Katharina Buerger^{13

25}, Robert Perneczky^{14

25

40

41}, Stefan Teipel^{18

19}, Christoph Laske^{20

42}, Oliver Peters^{7

22}, Emrah Düzel^{10

11}, Michael Wagner^{2

6}, Jiehui Jiang⁴³, Frank Jessen^{2

4

15}, Henning Boecker^{2

44}, Ying Han^{1

3

45

46}

Affiliations

¹ Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
² German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
³ Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou, China.
⁴ Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany.
⁵ Department of Neurology, University of Bonn, Bonn, Germany.
⁶ University of Bonn Medical Center, Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry, Bonn, Germany.
⁷ German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
⁸ Department of Psychiatry and Psychotherapy, Charité, Berlin, Germany.
⁹ Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen, Germany.
¹⁰ German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
¹¹ Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany.
¹² Department for Psychiatry and Psychotherapy, University Clinic Magdeburg, Magdeburg, Germany.
¹³ Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
¹⁴ Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
¹⁵ Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
¹⁶ Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.
¹⁷ Department of Psychiatry & Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, Texas, USA.
¹⁸ German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
¹⁹ Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany.
²⁰ German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany.
²¹ Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany.
²² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin-Institute of Psychiatry and Psychotherapy, Berlin, Germany.
²³ Berlin Center for Advanced Neuroimaging, Charité - Universitätsmedizin Berlin, Berlin, Germany.
²⁴ MR-Research in Neurosciences, Department of Cognitive Neurology, Georg-August-University Goettingen, Goettingen, Germany.
²⁵ German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
²⁶ Department for Biomedical Magnetic Resonance, University of Tuebingen, Tuebingen, Germany.
²⁷ Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
²⁸ Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
²⁹ Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.
³⁰ Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Germany.
³¹ Institute of Neuroscience and Medicine (INM-2), Molecular Organization of the Brain, Forschungszentrum Jülich, Germany.
³² Department of Nuclear Medicine, Ludwig-Maximilian-University Munich, Munich, Germany.
³³ Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
³⁴ Department of Nuclear Medicine, Rostock University Medical Centre, Rostock, Germany.
³⁵ Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard-Karls-University, Tuebingen, Germany.
³⁶ School of Medicine, Technical University of Munich, Department of Psychiatry and Psychotherapy, Munich, Germany.
³⁷ University of Edinburgh and UK DRI, Edinburgh, UK.
³⁸ German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany.
³⁹ Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.
⁴⁰ Munich Cluster for Systems Neurology (SyNergy) Munich, Munich, Germany.
⁴¹ Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College London, London, UK.
⁴² Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany.
⁴³ Institute of Biomedical Engineering, Shanghai University, Shanghai, China.
⁴⁴ Clinical Functional Imaging Group, Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Bonn, Germany.
⁴⁵ Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China.
⁴⁶ National Clinical Research Center for Geriatric Disorders, Beijing, China.

PMID: 37070734
DOI: 10.1002/alz.13068

Abstract

Introduction: It remains unclear whether functional brain networks are consistently altered in individuals with subjective cognitive decline (SCD) of diverse ethnic and cultural backgrounds and whether the network alterations are associated with an amyloid burden.

Methods: Cross-sectional resting-state functional magnetic resonance imaging connectivity (FC) and amyloid-positron emission tomography (PET) data from the Chinese Sino Longitudinal Study on Cognitive Decline and German DZNE Longitudinal Cognitive Impairment and Dementia cohorts were analyzed.

Results: Limbic FC, particularly hippocampal connectivity with right insula, was consistently higher in SCD than in controls, and correlated with SCD-plus features. Smaller SCD subcohorts with PET showed inconsistent amyloid positivity rates and FC-amyloid associations across cohorts.

Discussion: Our results suggest an early adaptation of the limbic network in SCD, which may reflect increased awareness of cognitive decline, irrespective of amyloid pathology. Different amyloid positivity rates may indicate a heterogeneous underlying etiology in Eastern and Western SCD cohorts when applying current research criteria. Future studies should identify culture-specific features to enrich preclinical Alzheimer's disease in non-Western populations.

Highlights: Common limbic hyperconnectivity across Chinese and German subjective cognitive decline (SCD) cohorts was observed. Limbic hyperconnectivity may reflect awareness of cognition, irrespective of amyloid load. Further cross-cultural harmonization of SCD regarding Alzheimer's disease pathology is required.

Keywords: Centiloid; amyloid deposition; cross-cultural harmonization; functional connectivity; hippocampus; insula; subjective cognitive decline.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / pathology
Amyloid beta-Peptides / metabolism
Brain / pathology
Cognitive Dysfunction*
Cross-Sectional Studies
East Asian People
European People
Humans
Magnetic Resonance Imaging
Positron-Emission Tomography

Altered limbic functional connectivity in individuals with subjective cognitive decline: Converging and diverging findings across Chinese and German cohorts

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