title: Midlife occupational cognitive requirements protect cognitive function in old age by increasing cognitive reserve
Creators: name: Kleineidam, Luca
name: Wolfsgruber, Steffen
name: Weyrauch, Anne-Sophie
name: Zulka, Linn E.
name: Forstmeier, Simon
name: Roeske, Sandra
name: Bussche, Hendrik van den
name: Kaduszkiewicz, Hanna
name: Wiese, Birgitt
name: Weyerer, Siegfried
name: Werle, Jochen
name: Fuchs, Angela
name: Pentzek, Michael
name: Brettschneider, Christian
name: König, Hans-Helmut
name: Weeg, Dagmar
name: Bickel, Horst
name: Luppa, Melanie
name: Rodriguez, Francisca S.
name: Freiesleben, Silka Dawn
name: Erdogan, Selin
name: Unterfeld, Chantal
name: Peters, Oliver
name: Spruth, Eike J.
name: Altenstein, Slawek
name: Lohse, Andrea
name: Priller, Josef
name: Fliessbach, Klaus
name: Kobeleva, Xenia
name: Schneider, Anja
name: Bartels, Claudia
name: Schott, Björn H.
name: Wiltfang, Jens
name: Maier, Franziska
name: Glanz, Wenzel
name: Incesoy, Enise I.
name: Butryn, Michaela
name: Düzel, Emrah
name: Buerger, Katharina
name: Janowitz, Daniel
name: Ewers, Michael
name: Rauchmann, Boris-Stephan
name: Perneczky, Robert
name: Kilimann, Ingo
name: Görß, Doreen
name: Teipel, Stefan
name: Laske, Christoph
name: Munk, Matthias H. J.
name: Spottke, Annika
name: Roy, Nina
name: Brosseron, Frederic
name: Heneka, Michael T.
name: Ramirez, Alfredo
name: Yakupov, Renat
name: Scherer, Martin
name: Maier, Wolfgang
name: Jessen, Frank
name: Riedel-Heller, Steffi G.
name: Wagner, Michael
Publisher: name: Frontiers Media S.A.
Year: 2024

description: 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.