Vascular risk factors for depression and apathy | Part II 150 attention in depression research, but we make a plea for paying a greater focus on apathy and the motivational symptoms of depression. We accordingly suggest including apathy as a separate outcome measure in intervention studies of depression, to gain more knowledge about which treatment reduces the risk of apathy in remitted depression. Such studies should preferably look at depression across the lifespan to enable researchers to chart the similarities and differences in the symptoms and prognosis of apathy in early- and late-life depression and in early- and late-onset depression. Another important consideration for future research the findings discussed in this thesis highlight is the complex interactions of the risk-factors for late-life depression, and the ceiling effects that can occur when more than one risk-factor is present. Each risk-factor alone contributes a certain amount to the risk of becoming depressed, but when by an accumulation of risks, the threshold effect is reached, the contribution of each individual factor might not be fully accounted for. Especially in severely symptomatic populations ceiling effect may often obscure clinical research findings 21. Although in the (near) future we may get more grip on individual risk-factors and their relative contributions and interactions by advances in statistics and big-data analyses, at this point our capabilities in predicting late-life depression in the individual are still limited. We are, however, able to identify the most determining risk-factors for late life-depression in well-defined populations, which information is particularly relevant for the development and implementation of dedicated prevention trials. If populations with a high vascular risk would profit from different depression-prevention methods than populations with a high risk because of high neuroticism is yet unknown. More differentiation not only in treatment options for depression, but also in prevention methods could pave the way to better outcomes. As to the CSVD-apathy relationship, there are still important gaps in our knowledge, where particularly prospective designs in which the progress of CSVD is studied in relation to the course of apathy over time are lacking. Moreover, in addition to depression and cognition, we recommend to include apathy as an outcome measure of brain health in intervention trials in patients with CSVD. Considerations for clinical practice What lessons can physicians learn from the research reported in this thesis? The first ´take-home message’ is that the relationship between cerebrovascular disease and latelife depression is bi-directional. The clinician is recommended to pay attention to the presence of vascular risks and vascular disease in older people going through a depression, but to likewise check for the presence of depression in older patients diagnosed with cerebrovascular disease. However, the clinical implication of these findings is as yet limited since the treatment of cerebrovascular disease in people coping with late-life depression does not differ from the general treatment of cerebrovascular disease, which also holds for the treatment of depression resulting from cerebrovascular disease. We also point to the risk of tunnel-vision when cerebrovascular disease is present. Cerebrovascular
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