Midlife occupational cognitive requirements protect cognitive function in old age by increasing cognitive reserve
Authors: Kleineidam Luca , Wolfsgruber Steffen , Weyrauch Anne-Sophie , Zulka Linn E. , Forstmeier Simon , Roeske Sandra , van den Bussche Hendrik , Kaduszkiewicz Hanna , Wiese Birgitt , Weyerer Siegfried , Werle Jochen , Fuchs Angela , Pentzek Michael , Brettschneider Christian , König Hans-Helmut , Weeg Dagmar , Bickel Horst , Luppa Melanie , Rodriguez Francisca S. , Freiesleben Silka Dawn , Erdogan Selin , Unterfeld Chantal , Peters Oliver , Spruth Eike J. , Altenstein Slawek , Lohse Andrea , Priller Josef , Fliessbach Klaus , Kobeleva Xenia , Schneider Anja , Bartels Claudia , Schott Björn H. , Wiltfang Jens , Maier Franziska , Glanz Wenzel , Incesoy Enise I. , Butryn Michaela , Düzel Emrah , Buerger Katharina , Janowitz Daniel , Ewers Michael , Rauchmann Boris-Stephan , Perneczky Robert , Kilimann Ingo , Görß Doreen , Teipel Stefan , Laske Christoph , Munk Matthias H. J. , Spottke Annika , Roy Nina , Brosseron Frederic , Heneka Michael T. , Ramirez Alfredo , Yakupov Renat , Scherer Martin , Maier Wolfgang , Jessen Frank , Riedel-Heller Steffi G. , Wagner Michael 
Published: December 2022

IntroductionSeveral 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.MethodsWe 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).ResultsRegarding (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.DiscussionOur 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.