Research Paper Volume 12, Issue 4 pp 3730—3746

The role of Apolipoprotein E epsilon4 in the association between psychosocial working conditions and dementia

Kuan-Yu Pan1, , Weili Xu1, , Francesca Mangialasche1,2, , Giulia Grande1, , Laura Fratiglioni1,3, , Hui-Xin Wang1,4, ,

  • 1 Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm 171 65, Sweden
  • 2 Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Solna 171 64, Sweden
  • 3 Stockholm Gerontology Research Center, Stockholm 113 30, Sweden
  • 4 Stress Research Institute, Stockholm University, Stockholm 114 19, Sweden

Received: October 18, 2019       Accepted: February 4, 2020       Published: February 20, 2020
How to Cite

Copyright © 2020 Pan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


In this population-based prospective study, we examined the association of job demand-control combinations with dementia, and explored the roles of Apolipoprotein E epsilon4 (APOE ɛ4) and work duration in this association. A total of 2,579 dementia-free individuals aged 60+ years from Sweden were followed over 12 years. Dementia diagnosis was made by physicians. Lifelong occupational experience was collected, and job demands and control were assessed using a psychosocial job-exposure matrix. Data were analyzed using multivariate Cox proportional hazard models. During the follow-up, 282 people developed dementia. Passive jobs (low control/low demands) were related to a higher risk of dementia compared with active jobs (high control/high demands) among the younger-old (aged ≤72 years), but not among the older-old (aged ≥78 years). Among the younger-old, compared to those with no passive job experience, those with 11+ years in passive jobs had a higher dementia risk. The joint-effect analyses showed that APOE ɛ4 carriers with passive jobs had an even higher risk of dementia compared to APOE ɛ4 non-carriers with active jobs. These findings suggest that passive jobs are related to a higher dementia risk among the younger-old. APOE ɛ4 and long work duration may amplify the impact of passive jobs on dementia.


APOE ɛ4: Apolipoprotein E epsilon4; CVD: Cardiovascular disease; KP: Kungsholmen Project; MMSE: Mini-Mental State Examination; SES: Socioeconomic Status; SNAC-K: Swedish National Study on Aging and Care-Kungsholmen.