Objective: To characterize earlier damage pattern of white matter (WM) microstructure in cerebral small vessel disease (CSVD) and its relationship with cognitive domain dysfunction.Methods: A total of 144 CSVD patients and 100 healthy controls who underwent neuropsychological measurements and diffusion tensor imaging (DTI) examination were recruited. Cognitive function, emotion, and gait were assessed in each participant. The automated fiber quantification (AFQ) technique was used to extract different fiber properties between groups, and partial correlation and general linear regression analyses were performed to assess the relationship between position-specific WM microstructure and cognitive function.Results: Specific segments in the association fibers, commissural WM regions of interest (ROIs), and projection fibers were damaged in the CSVD group [P < 0.05, family-wise error (FWE) correction], and these damaged segments showed interhemispheric symmetry. In addition, the damage to specific tract profiles [including the posteromedial component of the right cingulum cingulate (CC), the occipital lobe portion of the callosum forceps major, the posterior portion of the left superior longitudinal fasciculus (SLF), and the bilateral anterior thalamic radiation (ATR)] was related to the dysfunction in specific cognitive domains. Among these tracts, we found the ATR to be the key set of tracts whose profiles were most associated with cognitive dysfunction. The left ATR was a specific fiber bundle associated with episode memory and language function, whereas the fractional anisotropy (FA) values of the intermediate component of the right ATR were negatively correlated with executive function and gait evaluation. It should be noted that the abovementioned relationships could not survive the Bonferroni correction (p < 0.05/27), so we chose more liberal uncorrected statistical thresholds.Conclusions: Damage to the WM fiber bundles showed extensive interhemispheric symmetry and was limited to particular segments in CSVD patients. Disruption of strategically located fibers was associated with different cognitive deficits, especially the bilateral ATR.

Background Impaired cerebrovascular reactivity (CVR) plays an important role in the pathophysiology of white matter hyperintensities (WMHs). The pathogenesis of CVR in the development of WMH‐related cognitive impairment (CI) remains poorly understood. Purpose To detect the CVR status in WMH subjects with/without CI by using a resting‐state blood oxygenation level‐dependent (BOLD) approach and to explore the mediating relationships among CVR, WMH, and cognitive level. Study Type Prospective. Subjects Subjects with moderate to severe WMH (with CI [WMH‐CI], n = 68; without CI [WMH‐no‐CI, n = 63) as well as normal controls (NCs, n = 87). Field Strength/Sequence 3.0T with gradient‐recalled echoplanar imaging and 3D fluid‐attenuated inversion recovery. Assessment The CVR, WMH volume, and cognitive level were assessed. The CVR map was derived using BOLD signal obtained from resting‐state functional MRI data. Statistical Tests CVR maps were compared among the three groups. Partial correlation analyses were performed to correlate impaired CVR with WMH volume and cognitive test scores. Mediation analysis was conducted to determine whether WMH acted as a mediating factor between CVR and cognitive function. Results Compared with the NC group, both WMH groups showed reduced CVR in the left hemisphere (P < 0.05). The WMH‐CI group showed further decreased CVR in the left frontal area, when compared with the WMH‐no‐CI group (P < 0.05). In the WMH‐CI group, the lower CVR in left frontal area was a strong indicator of poor performance on general cognition (r = 0.311), executive function (r = 0.362), and information processing speed (r = 0.399) (all P < 0.05). Periventricular WMH (PWMH) volume mediated these correlations, the β and 95% bootstrap confidence intervals were (0.5097, [0.1498,1.1385]), (−0.4081, [−1.0256,‐0.1363]), and (−0.5576, [−1.4666,‐0.1538]), respectively. Data Conclusion WMH‐CI subjects showed a greater reduction of CVR derived from a resting‐state BOLD approach in the left frontal area than WMH‐no‐CI subjects. Cognition was highly dependent on the integrity of cerebrovascular reactivity and mediated by PWMH burden. Level of Evidence 4 Technical Efficacy Stage 2