Vascular risk factors for depression and apathy | Part II 134 The main limitation of this choice -the other side of the coin- is that in narrative review literature searches are not performed twice, the included studies are not as thoroughly weighed on quality by two authors as they would be in a structured review and data are not pooled as in a meta-analysis. Furthermore, we limited the sources of information to published articles, it would have been interesting to gather expert opinions, for instance by means of the Delphi method. Another limitation comes with applying the Bradford-Hill criteria to the CSVD-apathy association: there are no experimental data, only observational data 88 to support a causality claim. Conclusion Consistent pathophysiological evidence linking CSVD and apathy makes it plausible that CSVD can cause apathy. This causal relationship is supported by the evidence on the strength and biological gradient of the CSVD-apathy associations obtained in a diversity of populations, although the evidence for a temporal relationship is still weak. Given that there are often other factors in patients with CSVD that may cause or contribute to apathy, the specificity of the causal relationship can be said to be low. It is premature to speak of vascular apathy as if referring to a distinct clinical apathy syndrome, since differentiation between apathy syndromes on the basis of clinical features is unfeasible, while in-depth knowledge about differences in the prognosis and efficacy of dedicated treatment for apathy caused by CSVD and other apathy syndromes is lacking.
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