Related Experiment Video
Updated: Jan 25, 2026
Brain Infarct Segmentation and Registration on MRI or CT for Lesion-symptom Mapping
Published on: September 25, 2019
Impact of white matter hyperintensity location on depressive symptoms in memory-clinic patients: a lesion–symptom
Anna E. Leeuwis1, Nick A. Weaver1, J. Matthijs Biesbroek1
1From the Alzheimer Centre Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands (Leeuwis, Hooghiemstra, Prins, Scheltens, van der Flier); the Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, the Netherlands (Weaver, Biesbroek, Exalto, Biessels); the Image Sciences Institute, University Medical Centre Utrecht, Utrecht, the Netherlands (Kuijf); the Department of Medical Humanities, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands (Hooghiemstra); the Institutes of Neurology and Healthcare Engineering, UCL, London, United Kingdom (Barkhof); the Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands (Barkhof); and the Department of Epidemiology & Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands (Flier).
Background:
We investigated the association between white matter hyperintensity location and depressive symptoms in a memoryclinic 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 assumptionfree 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 (β = 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.
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