Cortical Thickness and Brain Connectivity Mediate the Relation Between White Matter Hyperintensity and Information Processing Speed in Cerebral Small Vessel Disease.

White matter hyperintensities of presumed vascular origin (WMH) are the most common imaging feature of cerebral small vessel disease (cSVD) and are associated with cognitive impairment, especially information processing speed (IPS) deficits. However, it is unclear how WMH can directly impact IPS or whether the cortical thickness and brain connectivity mediate such association. In this study, it was evaluated the possible mediating roles of cortical thickness and brain (structural and functional) connectivity on the relationship between WMH (also considering its topography distribution) and IPS in 389 patients with cSVD from the RUN-DMC (Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort) database. Significant (p < 0.05 after multiple comparisons correction) associations of WMH volume and topography with cortical thickness, brain connectivity, and IPS performance in cSVD individuals were found. Additionally, cortical thickness and brain structural and functional connectivity were shown to mediate the association of WMH volume and location with IPS scores. More specifically, frontal cortical thickness, functional sensorimotor network, and posterior thalamic radiation tract were the essential mediators of WMH and IPS in this clinical group. This study provided insight into the mechanisms underlying the clinical relevance of white matter hyperintensities in information processing speed deficits in cSVD through cortical thinning and network disruptions.

Neural Substrates of Psychomotor Speed Deficits in Cerebral Small Vessel Disease: A Brain Disconnectome Mapping Study.

It remains unknown which factors influence how brain disconnectivity derived from White Matter Hyperintensity (WMH) lesions leads to psychomotor speed dysfunction, one of the earliest and most common cognitive manifestations in the cerebral Small Vessel Disease (cSVD) population. While the burden of WMH has been strongly linked to psychomotor speed performance, the effect that different locations and volumes of WMH may have on cSVD-related cognitive impairment remains unclear. Therefore, we aimed to explore (1) whether global WMH, deep WMH (DWMH), and periventricular (PVWMH) volumes display different psychomotor speed associations; (2) whether tract-specific WMH volume shows stronger cognitive associations compared with global measures of WMH volume; (3) whether specific patterns of WMH location lead to different degrees of disconnectivity. Using the BCBToolkit, we investigated which pattern of distribution and which locations of WMH lesion result in impaired psychomotor speed in a well-characterized sample (n = 195) of cSVD patients without dementia. Two key findings emerge from our study. First, global (and not tract-specific) measures of WMH volume were associated with psychomotor speed performance. Second, disconnection maps revealed the involvement of callosal tracts, association and projection fibers, and frontal and parietal cortical brain areas related to psychomotor speed, while the lesion location influenced such associations. In conclusion, psychomotor deficits are affected differently by WMH burden and topographic distribution through brain disconnection in non-demented cSVD patients.