Background: The peak width of skeletonized mean diffusivity (PSMD) is a new, fully automated, robust imaging marker for cerebral small vessel disease (SVD), strongly associated with processing speed. However, it has never been applied to cerebral white matter lesions (WMLs). Our study aimed to investigate the correlation between PSMD and cognition, particularly in the executive function of patients with WMLs. Methods: A total of 111 WML patients and 50 healthy controls (HCs) were enrolled, and their demographic information and cardiovascular disease risk factors were recorded. Subjects were divided into three groups: WMLs with normal cognition (WMLs-NC), WMLs with vascular cognitive impairment (WMLs-VCI), and HCs. They underwent conventional head magnetic resonance imaging and diffusion tensor imaging (DTI), followed by neuropsychological and psychological examinations, including the Montreal Cognitive Assessment (MoCA), and the executive function tests. We compared executive function and PSMD among the three groups and analyzed the correlation between PSMD and cognitive function in all subjects. Results: There were no significant differences in demographic characteristics (age, sex, education level, and cardiovascular disease risk factors) among the three groups (P > 0.05), but there were significant differences in global cognition (P < 0.0001), executive function (P < 0.0001), and PSMD (P < 0.0001). The average PSMD value (×10^-4 mm²/s) was 2.40 ± 0.23, 2.68 ± 0.30, and 4.51 ± 0.39 in the HC, WMLs-NC, and WMLs-VCI groups, respectively. There was no correlation between PSMD and cognition in the HC group, but PSMD was significantly correlated with MoCA scores (r = -0.3785, P < 0.0001) and executive function (r = -0.4744, P < 0.0001) in the WMLs-NC group and in the WMLs-VCI group (r = -0.4448, P < 0.0001 and r = -0.6279, P < 0.0001, respectively). Conclusions: WML patients have higher PSMD and worse cognitive performance than HCs, and PSMD is strongly associated with global cognition and executive functions in WML patients. This result provides new insights into the pathophysiology of cognitive impairment in WML patients. PSMD could be a surrogate marker for disease progression and could thus be used in therapeutic trials involving WML patients.

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