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However, it is unclear what types of demands drive this effect and whether this effect is subject to a person's genetic risk. We investigated to what extent eight different types of mental demands at work together with the APOE e4 allele, a major risk gene for late\u2010onset Alzheimer's disease, affect cognitive functioning in late life.<\/jats:p><\/jats:sec>Methods\/Design<\/jats:title>The population\u2010based German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe, n = 2\u2009154) followed cognitively healthy individuals aged 75\u2009years and older in seven assessment waves. Cognitive functioning was assessed via the mini\u2010mental status examination.<\/jats:p><\/jats:sec>Results<\/jats:title>Mixed\u2010effects modeling (adjusted for education, gender, marital status, stroke, depression, and diabetes) indicated that participants who had an occupational history of working in jobs with high compared to low demands in \u201cLanguage & Knowledge\u201d, \u201cPattern detection\u201d, \u201cInformation processing\u201d, and \u201cService\u201d had a slower cognitive decline. APOE e4\u2010allele carriers had an accelerated cognitive decline, but this decline was significantly smaller if they had a medium compared to a low level of demands in contrast to non\u2010carriers.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Our longitudinal observations suggest that cognitive decline could be slowed by an intellectually enriched lifestyle even in risk gene carriers. 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