Midlife occupational cognitive requirements protect cognitive function in old age by increasing cognitive reserve

Luca Kleineidam; Steffen Wolfsgruber; Anne-Sophie Weyrauch; Linn E Zulka; Simon Forstmeier; Sandra Roeske; Hendrik van den Bussche; Hanna Kaduszkiewicz; Birgitt Wiese; Siegfried Weyerer; Jochen Werle; Angela Fuchs; Michael Pentzek; Christian Brettschneider; Hans-Helmut König; Dagmar Weeg; Horst Bickel; Melanie Luppa; Francisca S Rodriguez; Silka Dawn Freiesleben; Selin Erdogan; Chantal Unterfeld; Oliver Peters; Eike J Spruth; Slawek Altenstein; Andrea Lohse; Josef Priller; Klaus Fliessbach; Xenia Kobeleva; Anja Schneider; Claudia Bartels; Björn H Schott; Jens Wiltfang; Franziska Maier; Wenzel Glanz; Enise I Incesoy; Michaela Butryn; Emrah Düzel; Katharina Buerger; Daniel Janowitz; Michael Ewers; Boris-Stephan Rauchmann; Robert Perneczky; Ingo Kilimann; Doreen Görß; Stefan Teipel; Christoph Laske; Matthias H J Munk; Annika Spottke; Nina Roy; Frederic Brosseron; Michael T Heneka; Alfredo Ramirez; Renat Yakupov; Martin Scherer; Wolfgang Maier; Frank Jessen; Steffi G Riedel-Heller; Michael Wagner

doi:10.3389/fpsyg.2022.957308

Midlife occupational cognitive requirements protect cognitive function in old age by increasing cognitive reserve

Front Psychol. 2022 Dec 8:13:957308. doi: 10.3389/fpsyg.2022.957308. eCollection 2022.

Authors

Luca Kleineidam^{1

2}, Steffen Wolfsgruber², Anne-Sophie Weyrauch¹, Linn E Zulka^{1

3}, Simon Forstmeier⁴, Sandra Roeske², Hendrik van den Bussche⁵, Hanna Kaduszkiewicz^{5

6}, Birgitt Wiese⁷, Siegfried Weyerer⁸, Jochen Werle⁸, Angela Fuchs⁹, Michael Pentzek⁹, Christian Brettschneider¹⁰, Hans-Helmut König¹⁰, Dagmar Weeg¹¹, Horst Bickel¹¹, Melanie Luppa¹², Francisca S Rodriguez^{2

12}, Silka Dawn Freiesleben^{13

14

15}, Selin Erdogan^{13

14

15}, Chantal Unterfeld^{13

16}, Oliver Peters^{13

14

15}, Eike J Spruth^{13

17}, Slawek Altenstein^{13

17}, Andrea Lohse¹⁷, Josef Priller^{11

13

17

18}, Klaus Fliessbach^{1

2}, Xenia Kobeleva², Anja Schneider^{1

2}, Claudia Bartels¹⁹, Björn H Schott^{19

20

21}, Jens Wiltfang^{19

20

22}, Franziska Maier²³, Wenzel Glanz²⁴, Enise I Incesoy^{24

25}, Michaela Butryn²⁴, Emrah Düzel^{24

25}, Katharina Buerger^{26

27}, Daniel Janowitz²⁷, Michael Ewers^{26

27}, Boris-Stephan Rauchmann²⁸, Robert Perneczky^{26

28

29

30

31}, Ingo Kilimann^{32

33}, Doreen Görß³³, Stefan Teipel^{32

33}, Christoph Laske^{34

35}, Matthias H J Munk^{34

36}, Annika Spottke^{2

37}, Nina Roy², Frederic Brosseron², Michael T Heneka^{1

2}, Alfredo Ramirez^{1

2

38

39

40}, Renat Yakupov²⁴, Martin Scherer⁵, Wolfgang Maier¹, Frank Jessen^{2

23

38}, Steffi G Riedel-Heller¹², Michael Wagner^{1

2}

Affiliations

¹ Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
² German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
³ Department of Psychology and Centre for Ageing and Health (AgeCap), University of Gothenburg, Gothenburg, Sweden.
⁴ Developmental Psychology and Clinical Psychology of the Lifespan, University of Siegen, Siegen, Germany.
⁵ Department of Primary Medical Care, Center for Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁶ Medical Faculty, Institute of General Practice, University of Kiel, Kiel, Germany.
⁷ Center for Information Management, Hannover Medical School, Hanover, Germany.
⁸ Medical Faculty, Central Institute of Mental Health, Mannheim/Heidelberg University, Heidelberg, Germany.
⁹ Medical Faculty, Centre for Health and Society (CHS), Institute of General Practice (ifam), Heinrich Heine University, Düsseldorf, Germany.
¹⁰ Department of Health Economics and Health Services Research, Hamburg Center for Health Economics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Munich, Germany.
¹² Medical Faculty, Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Leipzig, Germany.
¹³ German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
¹⁴ Department of Psychiatry, Campus Berlin-Buch, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), Berlin, Germany.
¹⁵ Memory Clinic and Dementia Prevention Center, Experimental and Clinical Research Center (ECRC), Berlin, Germany.
¹⁶ Department of Psychiatry, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), Berlin, Germany.
¹⁷ Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹⁸ University of Edinburgh and UK DRI, Edinburgh, United Kingdom.
¹⁹ Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen, Germany.
²⁰ German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany.
²¹ Leibniz Institute for Neurobiology, Magdeburg, Germany.
²² Department of Medical Sciences, Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal.
²³ Department of Psychiatry, Medical Faculty, University of Cologne, Cologne, Germany.
²⁴ German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
²⁵ Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany.
²⁶ German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
²⁷ Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
²⁸ Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
²⁹ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
³⁰ Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College London, London, United Kingdom.
³¹ Sheeld Institute for Translational Neuroscience (SITraN), University of Sheeld, Sheeld, United Kingdom.
³² German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
³³ Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany.
³⁴ German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
³⁵ Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
³⁶ Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany.
³⁷ Department of Neurology, University of Bonn, Bonn, Germany.
³⁸ Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
³⁹ Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
⁴⁰ Department of Psychiatry and Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, TX, United States.

Abstract

Introduction: Several lifestyle factors promote protection against Alzheimer's disease (AD) throughout a person's lifespan. Although such protective effects have been described for occupational cognitive requirements (OCR) in midlife, it is currently unknown whether they are conveyed by brain maintenance (BM), brain reserve (BR), or cognitive reserve (CR) or a combination of them.

Methods: We systematically derived hypotheses for these resilience concepts and tested them in the population-based AgeCoDe cohort and memory clinic-based AD high-risk DELCODE study. The OCR score (OCRS) was measured using job activities based on the O*NET occupational classification system. Four sets of analyses were conducted: (1) the interaction of OCR and APOE-ε4 with regard to cognitive decline (N = 2,369, AgeCoDe), (2) association with differentially shaped retrospective trajectories before the onset of dementia of the Alzheimer's type (DAT; N = 474, AgeCoDe), (3) cross-sectional interaction of the OCR and cerebrospinal fluid (CSF) AD biomarkers and brain structural measures regarding memory function (N = 873, DELCODE), and (4) cross-sectional and longitudinal association of OCR with CSF AD biomarkers and brain structural measures (N = 873, DELCODE).

Results: Regarding (1), higher OCRS was associated with a reduced association of APOE-ε4 with cognitive decline (mean follow-up = 6.03 years), consistent with CR and BR. Regarding (2), high OCRS was associated with a later onset but subsequently stronger cognitive decline in individuals converting to DAT, consistent with CR. Regarding (3), higher OCRS was associated with a weaker association of the CSF Aβ42/40 ratio and hippocampal volume with memory function, consistent with CR. Regarding (4), OCR was not associated with the levels or changes in CSF AD biomarkers (mean follow-up = 2.61 years). We found a cross-sectional, age-independent association of OCRS with some MRI markers, but no association with 1-year-change. OCR was not associated with the intracranial volume. These results are not completely consistent with those of BR or BM.

Discussion: Our results support the link between OCR and CR. Promoting and seeking complex and stimulating work conditions in midlife could therefore contribute to increased resistance to pathologies in old age and might complement prevention measures aimed at reducing pathology.

Keywords: Alzheimer's disease; brain maintenance; brain reserve; cognitive reserve; mid-life cognitive demands; occupation.

Copyright © 2022 Kleineidam, Wolfsgruber, Weyrauch, Zulka, Forstmeier, Roeske, van den Bussche, Kaduszkiewicz, Wiese, Weyerer, Werle, Fuchs, Pentzek, Brettschneider, König, Weeg, Bickel, Luppa, Rodriguez, Freiesleben, Erdogan, Unterfeld, Peters, Spruth, Altenstein, Lohse, Priller, Fliessbach, Kobeleva, Schneider, Bartels, Schott, Wiltfang, Maier, Glanz, Incesoy, Butryn, Düzel, Buerger, Janowitz, Ewers, Rauchmann, Perneczky, Kilimann, Görß, Teipel, Laske, Munk, Spottke, Roy, Brosseron, Heneka, Ramirez, Yakupov, Scherer, Maier, Jessen, Riedel-Heller and Wagner.