Part 1 | Vascular risk factors for depression and apathy 71 4 three-way interaction between gender, neuroticism and vascular disease, supported our stratification for gender in subsequent analyses on the combined effects of vascular disease and neuroticism. In women, no relationship could be detected between vascular disease and CRDS, in contrast to men. This gender-difference in the effect of vascular disease might be explained by the fact that in women the same stage of vascular disease is present at a later age (10-15 years) than in men 41. Furthermore, vascular diseases in women have a different presentation and are not as well detected as in men 25. However, these explanations should be interpreted cautiously because there was a small number of depressed women with both vascular disease and a low level of neuroticism in this study. In elderly men we found a negative interaction between vascular disease and neuroticism. A high level of vascular disease did reduce rather than raise the depressogenic potential of neuroticism in this large epidemiological study. This adds credibility to similar results from a small case-control design in a mixed gender population 22. This negative interaction effect between neuroticism and vascular disease clearly differs from the positive interaction effects between neuroticism and life events 18 or disability 19 which led to raise the levels of depressive symptoms. How could we explain the negative interaction effect between neuroticism and cardiac disease in men? There is the possibility of a ceiling effect at the highest levels of both neuroticism and cardiac disease, suggesting that some pathways in which vascular disease leads to depressive symptoms are shared with pathways of neuroticism. Common pathways could be inflammatory processes 42 43 44 and (associated) hypothalamic-pituitaryadrenal axis functioning 45 46 47. Our results suggest that, in men, the biological changes that occur in the brain because of vascular disease override some of the independent pathways of neuroticism to depressive symptoms. A similar mechanism was seen by Archer et al. (2007) 48: in their study the presence of Alzheimer’s disease attenuated the association between neuroticism and depression. Several studies have shown that vascular disease is associated with apathy 49 50. We speculate that the presence of apathy might temper the effect of neuroticism by reducing attention or reducing responsiveness to stress. This would be an interesting topic for future research. Limitations There are some limitations to these results. First, the direction of relationships could not be established because of the cross-sectional design of this study. Secondly, self-report measurements were used. And although the CES-D is a well-validated measurement for the detection of depressive symptoms in the elderly, its specificity for major depression is less than 100% (namely 88%, following Beekman et al. 1997) 28. However, subsyndromal depressive states form a continuum with major depression, also with regard to the relationship with neuroticism 51 18. Self-reported vascular disease has been compared with physician reports in a number of studies. Very good concordance has been found for self- reported and physician reported diabetes mellitus, good concordance for hypertension
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