Occupational exposures and risk of dementia-related mortality in the prospective Netherlands Cohort Study

Occupational exposures and risk of dementia-related mortality in the prospective Netherlands Cohort Study

Koeman T, Schouten LJ, van den Brandt PA, Slottje P, Huss A, Peters S, Kromhout H, Vermeulen R. Occupational exposures and risk of dementia-related mortality in the prospective Netherlands Cohort Study. Am J Ind Med. 2015 May 5. doi: 10.1002/ajim.22462. [Epub ahead of print]

Abstract

BACKGROUND: Occupational exposures may be associated with non-vascular dementia.

METHODS: We analyzed the effects of occupational exposures to solvents, pesticides, metals, extremely low frequency magnetic fields (ELF-MF), electrical shocks, and diesel motor exhaust on non-vascular dementia related mortality in the Netherlands Cohort Study (NLCS). Exposures were assigned using job-exposure matrices. After 17.3 years of follow-up, 682 male and 870 female cases were available. Analyses were performed using Cox regression.

RESULTS: Occupational exposure to metals, chlorinated solvents and ELF-MF showed positive associations with non-vascular dementia among men, which seemed driven by metals (hazard ratio ever high vs. background exposure: 1.35 [0.98-1.86]). Pesticide exposure showed statistically significant, inverse associations with non-vascular dementia among men. We found no associations for shocks, aromatic solvents, and diesel motor exhaust.

CONCLUSIONS: Consistent positive associations were found between occupational exposure to metals and non-vascular dementia. The finding on pesticides is not supported in the overall literature. 

Excerpts

Correlation analyses between the different occupational exposures among men revealed two main exposure clusters (see Fig. 1). One cluster contained metal, solvent, ELF-MF, and electrical shock exposures. This cluster could be attributed to high exposure levels for subjects working in the metal industry. The other cluster, containing exposure to pesticides, insecticides, herbicides, fungicides, and diesel motor exhaust, could be attributed to high exposure levels among farmers. Correlations between occupational exposures among women were low (see Fig. S1).


We used a prospective study design to analyze the effects of selected occupational exposures on non-vascular dementia risk. We observed a consistent positive association in the ever/never and the cumulative exposure analyses between chlorinated solvents and metals and non-vascular dementia related mortality. The association with metal exposure was corroborated by the observation of an increased risk of non-vascular dementia among women with ever high exposure to metals. The robustness of the metal effect in the bivariate combined exposure models in men further indicates that the positive associations with ELF-MF and chlorinated solvents in the single occupational exposure analysis might be attributable to metals. Unexpectedly, exposure to pesticides showed a significant, negative association with non-vascular dementia related mortality in men, both in the ever/never analyses and in the cumulative exposure analyses, which were retained when combined exposures were considered.

Studies on the association between occupational exposure to ELF-MF and Alzheimer's disease have shown positive associations [Savitz et al., 1998a; Feychting et al., 2003; Håkansson et al., 2003; Roosli et al., 2007]. However, these associations have not been present in all studies [Savitz et al., 1998a; Sorahan and Kheifets, 2007], or were limited to specific subgroups [Park et al., 2005]. A meta-analysis showed an increased risk of Alzheimer's disease with higher levels of ELF-MF exposure, with case-control studies providing a stronger pooled association than cohort studies [Garcia et al., 2008]. In our cohort study we found an association between ever high occupational versus background ELF-MF exposure and non-vascular dementia related mortality in men, but not with cumulative, occupational ELF-MF exposure. Therefore, our study provides only limited support for a possible association between occupational ELF-MF exposure and non-vascular dementia.

Electric shocks have been proposed as an alternative explanation for the possible association between ELF-MF exposure and amyotrophic lateral sclerosis [Håkansson et al., 2003]. No such proposal has been made for Alzheimer's disease nor has an association between electrical shocks and dementia or Alzheimer's disease been addressed in prior publications. In our study we did find indications for an association between electrical shocks and non-vascular dementia mortality in women. However, because this association was only found among women and not among men, and the number of high exposed female cases was very low (approximately 1% of all female cases), we could not explore cumulative or combined exposures. Hence this observation should be interpreted with caution.


In conclusion, exposure to metals showed a consistent, positive association with non-vascular dementia among men and women.Occupational exposure to chlorinated solvents and to ELF-MF also showed associations with non-vascular dementia in men, but these associations seemed more likely attributable to exposure to metals with which they were highly correlated.

--
Joel M. Moskowitz, Ph.D., Director
Center for Family and Community Health
School of Public Health
University of California, Berkeley

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