Part II | Vascular risk factors for depression and apathy 127 7 Although, all in all, we can safely conclude that there is a dose-response relationship between CSVD and apathy in a diversity of populations, these results could do with replication. And particularly the association between the total CSVD burden and the severity of apathy needs further looking into, since this might be a more accurate biomarker for underlying network disruption. Temporality Prospective studies supporting an association between CSVD at baseline and apathy at follow-up, or between CSVD progression and changes in apathy scores over time, add credibility to a causal relationship. Neuroimaging studies assessing frontal subcortical atrophy or WMH within 24 hours of a stroke found an association with apathy at 3 to 6 months of follow-up 55 37 56, barring a small scale study 36. A study in which neuroimaging was conducted 3 months post-stroke and apathy assessed the next year also found no evidence of an association 39. A study comparing baseline WMH volumes and apathy severity scores after 5 years in otherwise healthy individuals also found no evidence linking baseline WMH values to changes in apathy 57. A study aiming to compare the differences in the course of neuropsychiatric symptoms between patients with Alzheimer´s disease and vascular dementia patients with WMH and lacunar infarcts on neuroimaging, found a higher level of apathy and a significant increase in apathy in the latter group, which was not related to cognitive decline 58. The baseline WMH volumes of depressed patients receiving electric convulsive treatment (ECT) did not predict apathy post ECT but remaining depressive symptomatology and apathy at baseline did 32. All in all, the temporal relationship between CSVD and apathy has some empirical support but this is thus far limited to stroke patients. Of note is that all these studies looked at the association between baseline WMH and apathy at follow-up. Studies investigating the progression of CSVD or WMH over time and its relation to changes in apathy were still lacking. Consistency Are the reported associations between (markers of) CSVD and apathy consistent across a diversity of populations and contexts? Mostly, the evidence was obtained in healthy (older) adults and individuals with cognitive deficits and/or stroke 7 30. The few studies that specifically studied the WMH-apathy association in individuals with Parkinson’s disease showed that apathy was predicted by WMH integrity 59 and that apathy severity was associated with WMH severity 60. In depression, or after depression, findings are inconsistent. No association was found in older adults stills showing apathy following ECT for depression 32, but in depressed age peers who showed remaining symptoms of apathy after treatment with citalopram an association was found with white matter (and anterior cingulate) volumes 31, while WMH correlated with apathy in older adults with severe late-onset depression 33, but not in those with severe early-onset depression. Possible explanations for these inconsistencies will be discussed in the Specificity section.
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