Psychosocial stress has been shown to contribute to neurodegenerative changes and has been discussed as a pathogenic element in Alzheimer's disease (AD). However, studies investigating this aspect are rare. We performed a case-control study on 50 clinically diagnosed probable AD patients and 90 controls consisting of surgical patients. Interviews were performed by trained personnel, using a questionnaire, a semi-structured interview, and a psychosocial risk list protocol. Findings are presented as marginal and partial odds ratio from linear logistic regressions. Adapting to an active but unproductive working style as well as living with a dominant spouse is associated with significant risk for AD. Protective factors are high self-esteem and working in one's desired job. Our results indicate psychosocial factors as a possible agent in the latent development of AD and may shift the focus from more traditional risk factors to hitherto almost neglected psychosocial factors in a disease of still unknown etiology.