Background We investigated the association between white matter hyperintensity location and depressive symptoms in a memory-clinic population using lesion-symptom mapping. Methods We included 680 patients with vascular brain injury from the TRACE-VCI cohort (mean age +/- standard deviation: 67 +/- 8 years; 52% female): 168 patients with subjective cognitive decline, 164 with mild cognitive impairment and 348 with dementia. We assessed depressive symptoms using the Geriatric Depression Scale. We applied assumption-free voxel-based lesion-symptom mapping, adjusted for age, sex, total white matter hyperintensity volume and multiple testing. Next, we applied exploratory region-of-interest linear regression analyses of major white matter tracts, with additional adjustment for diagnosis. Results Voxel-based lesion-symptom mapping identified voxel clusters related to the Geriatric Depression Scale in the left corticospinal tract. Region-of-interest analyses showed no relation between white matter hyperintensity volume and the Geriatric Depression Scale, but revealed an interaction with diagnosis in the forceps minor, where larger regional white matter hyperintensity volume was associated with more depressive symptoms in subjective cognitive decline (beta = 0.26, p < 0.05), but not in mild cognitive impairment or dementia. Limitations We observed a lack of convergence of findings between voxel-based lesion-symptom mapping and region-of-interest analyses, which may have been due to small effect sizes and limited lesion coverage despite the large sample size. This warrants replication of our findings and further investigation in other cohorts. Conclusion This lesion-symptom mapping study in depressive symptoms indicates the corticospinal tract and forceps minor as strategic tracts in which white matter hyperintensity is associated with depressive symptoms in memory-clinic patients with vascular brain injury. The impact of white matter hyperintensity on depressive symptoms is modest, but it appears to depend on the location of white matter hyperintensity and disease severity.
Bibliographical noteAcknowledgements: The TRACE-VCI study is supported by Vidi
grant 91711384 and Vici Grant 918.16.616 from ZonMw, the Netherlands, Organisation for Health Research and Development, and
grant 2010T073 from the Dutch Heart Association to G. Biessels. Research of the VUmc Alzheimer Centre is part of the neurodegeneration research program of Amsterdam Neuroscience. The VUmc Alzheimer Centre is supported by Alzheimer Nederland and Stichting
VUmc Fonds. The clinical database structure was developed with
funding from Stichting Dioraphte. A. Leeuwis and A. Hooghiemstra
are appointed on a grant from The Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation (CVON 2012-06 Heart
Brain Connection). F. Barkhof is supported by the NIHR Biomedical
Research Centre at University College London Hospital.