Amyloid and SCD jointly predict cognitive decline across Chinese and German cohorts

Author:

Shao Kai123,Hu Xiaochen23,Kleineidam Luca24,Stark Melina24,Altenstein Slawek56,Amthauer Holger7,Boecker Henning28,Buchert Ralph910,Buerger Katharina1112,Butryn Michaela1314,Cai Yanning15,Cai Yue16,Cosma Nicoleta Carmen17,Chen Guanqun18,Chen Zhigeng19,Daamen Marcel2,Drzezga Alexander22021,Düzel Emrah1314,Essler Markus22,Ewers Michael1112,Fliessbach Klaus24,Gaertner Florian C.22,Glanz Wenzel1314,Guo Tengfei16,Hansen Niels23,He Beiqi24,Janowitz Daniel12,Kilimann Ingo2526,Krause Bernd J.27,Lan Guoyu1628,Lange Catharina7,Laske Christoph2930,Li Yuxia31,Li Ruixian1,Liu Lin1628,Lu Jie19,Meng Fansheng32,Munk Matthias H.2933,Peters Oliver517,Perneczky Robert11343536,Priller Josef563738,Ramirez Alfredo24394041,Rauchmann Boris‐Stephan344243,Reimold Matthias44,Rominger Axel4546,Rostamzadeh Ayda3,Roy‐Kluth Nina2,Schneider Anja24,Spottke Annika247,Spruth Eike Jakob56,Sun Pan1628,Teipel Stefan2526,Wang Xiao17,Wei Min1,Wei Yongzhe1,Wiltfang Jens234849,Yan Shaozhen1920,Yang Jie1,Yu Xianfeng1,Zhang Mingkai1,Zhang Liang24,Wagner Michael24,Jessen Frank2339,Han Ying116505152,Kuhn Elizabeth24ORCID,

Affiliation:

1. Department of Neurology XuanWu Hospital of Capital Medical University Beijing China

2. German Center for Neurodegenerative Diseases (DZNE) Bonn Germany

3. Department of Psychiatry Medical Faculty University of Cologne Cologne Germany

4. Department of Old Age Psychiatry and Cognitive Disorders University of Bonn Medical Center Bonn Germany

5. German Center for Neurodegenerative Diseases (DZNE) Berlin Germany

6. Department of Psychiatry and Psychotherapy Charité Berlin Germany

7. Department of Nuclear Medicine Charité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, and Humboldt‐Universität zu Berlin Berlin Germany

8. Clinical Functional Imaging Group, Department of Diagnostic and Interventional Radiology University Hospital Bonn Bonn Germany

9. Department of Nuclear Medicine Charité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, and Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin Germany

10. Department of Diagnostic and Interventional Radiology and Nuclear Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany

11. German Center for Neurodegenerative Diseases (DZNE, Munich) Munich Germany

12. Institute for Stroke and Dementia Research (ISD) University Hospital, LMU Munich Munich Germany

13. German Center for Neurodegenerative Diseases (DZNE) Magdeburg Germany

14. Institute of Cognitive Neurology and Dementia Research (IKND) Otto‐von‐Guericke University Magdeburg Germany

15. Department of clinical biobank XuanWu Hospital of Capital Medical University Beijing China

16. Institute of Biomedical Engineering Shenzhen Bay Laboratory Shenzhen China

17. Department of Psychiatry and Psychotherapy Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu Berlin Berlin Germany

18. Department of Neurology Beijing ChaoYang Hospital of Capital Medical University Beijing China

19. Department of Radiology and Nuclear Medicine XuanWu Hospital of Capital Medical University Beijing China

20. Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne University of Cologne Cologne Germany

21. Institute of Neuroscience and Medicine (INM‐2) Molecular Organization of the Brain, Forschungszentrum Jülich Jülich Germany

22. Department of Nuclear Medicine University Hospital Bonn Bonn Germany

23. Department of Psychiatry and Psychotherapy, University Medical Center Goettingen University of Goettingen Goettingen Germany

24. School of Information and Communication Engineering Hainan University Haikou China

25. German Center for Neurodegenerative Diseases (DZNE) Rostock Germany

26. Department of Psychosomatic Medicine Rostock University Medical Center Rostock Germany

27. Department of Nuclear Medicine Rostock University Medical Centre Rostock Germany

28. Tsinghua Shenzhen International Graduate School (SIGS) Tsinghua University Shenzhen China

29. German Center for Neurodegenerative Diseases (DZNE) Tübingen Germany

30. Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy University of Tübingen Tübingen Germany

31. Department of Neurology Tangshan Central Hospital Tanshan China

32. Medical Imaging Department of Hainan Cancer Hospital Haikou China

33. Department of Psychiatry and Psychotherapy University of Tübingen Tübingen Germany

34. Department of Psychiatry and Psychotherapy University Hospital, LMU Munich Munich Germany

35. Munich Cluster for Systems Neurology (SyNergy) Munich Munich Germany

36. Ageing Epidemiology Research Unit (AGE), School of Public Health Imperial College London London UK

37. University of Edinburgh and UK DRI Edinburgh UK

38. School of Medicine, Department of Psychiatry and Psychotherapy Technical University of Munich Munich Germany

39. Excellence Cluster on Cellular Stress Responses in Aging‐Associated Diseases (CECAD) University of Cologne Köln Germany

40. Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne University of Cologne Köln Germany

41. Department of Psychiatry & Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases San Antonio Texas USA

42. Sheffield Institute for Translational Neuroscience (SITraN) University of Sheffield Sheffield UK

43. Department of Neuroradiology University Hospital LMU Munich Germany

44. Department of Nuclear Medicine and Clinical Molecular Imaging Eberhard‐Karls‐University Tuebingen Germany

45. Department of Nuclear Medicine Ludwig‐Maximilian‐University Munich Munich Germany

46. Department of Nuclear Medicine, Inselspital, Bern University Hospital University of Bern Bern Switzerland

47. Department of Neurology University of Bonn Bonn Germany

48. German Center for Neurodegenerative Diseases (DZNE) Goettingen Germany

49. Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences University of Aveiro Aveiro Portugal

50. School of Biomedical Engineering Hainan University Haikou China

51. Center of Alzheimer's Disease Beijing Institute for Brain Disorders Beijing China

52. National Clinical Research Center for Geriatric Disorders Beijing China

Abstract

AbstractINTRODUCTIONSubjective cognitive decline (SCD) in amyloid‐positive (Aβ+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies.METHODSEight hundred twenty‐one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers. Global cognitive change was analyzed using linear mixed‐effects models.RESULTSIn the combined and stratified cohorts, Aβ+ participants with SCD showed steeper cognitive decline or diminished practice effects compared with NC or Aβ− participants with SCD. These findings were confirmed using different operationalizations of SCD and amyloid positivity, and across different SCD recruitment settings.DISCUSSIONAβ+ individuals with SCD in German and Chinese populations showed greater global cognitive decline and could be targeted for interventional trials.Highlights SCD in amyloid‐positive (Aβ+) participants predicts a steeper cognitive decline. This finding does not rely on specific SCD or amyloid operationalization. This finding is not specific to SCD patients recruited from memory clinics. This finding is valid in both German and Chinese populations. Aβ+ older adults with SCD could be a target population for interventional trials.

Funder

National Natural Science Foundation of China

Deutsches Zentrum für Neurodegenerative Erkrankungen

China Scholarship Council

Publisher

Wiley

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