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

Kai Shao^{1

2

3}, Xiaochen Hu^{2

3}, Luca Kleineidam^{2

4}, Melina Stark^{2

4}, Slawek Altenstein^{5

6}, Holger Amthauer⁷, Henning Boecker^{2

8}, Ralph Buchert^{9

10}, Katharina Buerger^{11

12}, Michaela Butryn^{13

14}, Yanning Cai¹⁵, Yue Cai¹⁶, Nicoleta Carmen Cosma¹⁷, Guanqun Chen¹⁸, Zhigeng Chen¹⁹, Marcel Daamen², Alexander Drzezga^{2

20

21}, Emrah Düzel^{13

14}, Markus Essler²², Michael Ewers^{11

12}, Klaus Fliessbach^{2

4}, Florian C Gaertner²², Wenzel Glanz^{13

14}, Tengfei Guo¹⁶, Niels Hansen²³, Beiqi He²⁴, Daniel Janowitz¹², Ingo Kilimann^{25

26}, Bernd J Krause²⁷, Guoyu Lan^{16

28}, Catharina Lange⁷, Christoph Laske^{29

30}, Yuxia Li³¹, Ruixian Li¹, Lin Liu^{16

28}, Jie Lu¹⁹, Fansheng Meng³², Matthias H Munk^{29

33}, Oliver Peters^{5

17}, Robert Perneczky^{11

34

35

36}, Josef Priller^{5

6

37

38}, Alfredo Ramirez^{2

4

39

40

41}, Boris-Stephan Rauchmann^{34

42

43}, Matthias Reimold⁴⁴, Axel Rominger^{45

46}, Ayda Rostamzadeh³, Nina Roy-Kluth², Anja Schneider^{2

4}, Annika Spottke^{2

47}, Eike Jakob Spruth^{5

6}, Pan Sun^{16

28}, Stefan Teipel^{25

26}, Xiao Wang¹⁷, Min Wei¹, Yongzhe Wei¹, Jens Wiltfang^{23

48

49}, Shaozhen Yan^{19

20}, Jie Yang¹, Xianfeng Yu¹, Mingkai Zhang¹, Liang Zhang²⁴; DELCODE study group, SILCODE study group; Michael Wagner^{2

4}, Frank Jessen^{2

3

39}, Ying Han^{1

16

50

51

52

53}, Elizabeth Kuhn^{2

4}

Affiliations

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.
⁵³ The Central Hospital of Karamay, Xinjiang, China.

PMID: 39072956
PMCID: PMC11497667
DOI: 10.1002/alz.14119

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

Kai Shao et al. Alzheimers Dement. 2024 Sep.

. 2024 Sep;20(9):5926-5939.

doi: 10.1002/alz.14119. Epub 2024 Jul 27.

Authors

Affiliations

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.
⁵³ The Central Hospital of Karamay, Xinjiang, China.

PMID: 39072956
PMCID: PMC11497667
DOI: 10.1002/alz.14119

Abstract

Introduction: Subjective 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.

Methods: Eight 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.

Results: In 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.

Discussion: Aβ+ 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.

Keywords: PET; Stage 2 Alzheimer's disease; amyloid pathology; cognitive decline; cross‐cultural study; longitudinal design; plasma Aβ42/40 ratio; subjective cognitive decline.

PubMed Disclaimer

Conflict of interest statement

The authors declare no relevant competing interests. Author disclosures are available in the supporting information.

Figures

**FIGURE 1**
Longitudinal cognitive performance according to baseline categorical SCD definition combined with baseline amyloid status. Plots are derived from linear mixed‐effects models looking at (A) the two‐way interaction between time and group (Model 1) and (B) the three‐way interaction between time, group, and cohort (Model 2), with cognitive measures (z‐composite score in SILCODE or PACC5 score in DELCODE) as outcome. Aβ, amyloid beta; CLoCODE, Cross–Cultural Longitudinal Study on Cognitive Decline; DELCODE, DZNE‐Longitudinal Cognitive Impairment and Dementia Study; Est, estimate; PACC5, Preclinical Alzheimer's Cognitive Composite; SE, standard error; SILCODE, Sino Longitudinal Study on Cognitive Decline.

**FIGURE 2**
Longitudinal cognitive performance according to baseline Ecog levels and amyloid status. Plots are derived from linear mixed‐effects models looking at (A) the three‐way interaction among time, Ecog, and amyloid status (Model 3) and (B) the four‐way interaction among time, Ecog, amyloid status, and cohort (Model 4), with cognitive measure (z‐composite score in SILCODE or PACC5 score in DELCODE) as outcome. For visualization purposes, Ecog levels are divided here into quartiles with lower, median, and upper modelized as separate lines (the lower quartile is 1.08, the median is 1.25, the upper quartile is 1.58). Aβ, amyloid beta; CLoCODE, Cross–Cultural Longitudinal Study on Cognitive Decline; DELCODE, DZNE‐Longitudinal Cognitive Impairment and Dementia Study; Ecog, self‐reported 12‐item short form of Everyday Cognition questionnaire; Est, estimate; PACC5, Preclinical Alzheimer's Cognitive Composite; SE, standard error; SILCODE, Sino Longitudinal Study on Cognitive Decline.

**FIGURE 3**
Longitudinal cognitive performances according to recruitment setting combined with amyloid status in SILCODE. Plots are derived from linear mixed‐effects models (Model 5) looking at two‐way interaction between time and six groups based on the combination of recruitment setting (ie, NC, SCDcom, SCDclin) and baseline amyloid status (derived from PET and plasma data combined). Aβ, amyloid beta; Est, estimate; NC, normal control; SCD, subjective cognitive decline; SCDcom, SCD recruited from community; SCDclin, SCD recruited from memory clinic; SE, standard error; SILCODE, Sino Longitudinal Study on Cognitive Decline.

See this image and copyright information in PMC

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

Affiliations

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

Authors

Affiliations

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Conflict of interest statement

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