Three types of white matter hyperintensities have different effects on depression and cognitive function in patients with CADASIL

Background White matter hyperintensities (WMH) according to the distance to the ventricle have been associated with different clinical, histopathological, and etiological correlates, which may provide the clues for understanding pathophysiology of many geriatric syndromes associated with WMH. The purpose of this study was to investigate the effects of WMH on depression and cognitive function in patients with CADASIL according to the locations of WMH. Method 84 subjects with CADASIL, aged 34–86 years, participated in this study. They underwent comprehensive clinical evaluation, including 3T MRI and genotyping of NOTCH3. With new subclassification of WMH (Kim, 2008), WMH were subclassified into juxtaventricular WMH (JVWMH), periventricular WMH (PVWMH), and deep WMH (DWMH) according to the distance to the ventricle. Lesions were segmented by the lesion prediction algorithm (Schmidt, 2017, Chapter 6.1) as implemented in the LST toolbox version 3.0.0 (www.statistical‐modelling.de/lst.html) for SPM. WMH volume was corrected as a ratio of the WMH volume to total intracranial volume. Result Using linear regression model after controlling for age, only JVWMH volume was associated with the scores of geriatric depression scale (GDS) (p=0.027) and CES‐D (p=0.041) among 3 types of WMH. There were no association trends between DWMH volume and scores of GDS (p=0.641) and CES‐D (p=0.427). After controlling age, education and sex, JVMMH volume was associated with poor performances in Categorical Verbal Fluency Test (cVFT) (P=0.013), 15‐item Boston Naming Test (sBNT) (P=0.020), Word List Memory Test (WLMT) (P=0.006), Word List Recall Test (WLRT) (P=0.010), Constructional Recall Test (CRT) (P=0.012), and Trail Making Test A and B (TMT‐A and TMT‐B) (p=0.003, p=0.004). PVWMH volume was associated with poor performances with in cVFT (P=0.027) and WLMT (P=0.031). DWMH volume had no associations with the scores of CERAD neuropsychological tests. Conclusion JVWMH are closely associated with depression and various domains of cognitive function. However, DWMH have no association with both depression and cognitive decline. 3 Types of WMH have different effects on depression and cognitive function in patients with CADASIL.