The mediating role of white matter hyperintensity in the association between malnutrition and cognitive impairment in patients with cerebral small vessel disease.

BACKGROUND: Malnutrition and white matter hyperintensity (WMH) are both considered risk factors for cognitive impairment in patients with cerebral small vessel disease (CSVD). However, the associations among nutritional status, WMH burden, and cognitive function remain unclear. This study aimed to investigate the mediating role of WMH volume in malnutrition and cognitive impairment in CSVD patients. METHODS: We conducted a retrospective cross-sectional study of 383 patients with CSVD. Nutritional status and cognitive function were assessed via the Geriatric Nutritional Risk Index (GNRI) and the Montreal Cognitive Assessment (MoCA), respectively. WMH volumes were quantified using VB-Net automatic segmentation. WMH volumes were natural log-transformed using ln(volume + 1) before linear regression and mediation analyses. The associations among GNRI, WMH volume, and MoCA scores were examined using Spearman correlation, multivariable linear regression, and mediation analyses. RESULTS: Patients with cognitive impairment had significantly lower GNRI scores compared to those with normal cognition. Patients with cognitive impairment presented with significantly larger volumes of total WMH, deep WMH (DWMH), periventricular WMH (PVWMH), and juxtacortical WMH (JCWMH) compared to patients with normal cognition. Spearman correlation analysis indicated significant correlations between GNRI scores, WMH volumes, and MoCA scores. Multivariable regression analysis showed that higher GNRI scores were associated with higher MoCA scores, whereas greater log-transformed WMH volumes were associated with lower MoCA scores. Mediation analysis showed that log-transformed total WMH significantly mediated the association between GNRI and MoCA scores, accounting for 70.7% of the relative effect, with an indirect effect of 0.1490 and a 95% bootstrap CI of 0.1007-0.2054. Among WMH subtypes, PVWMH showed the largest relative mediation effect, accounting for 72.6%, followed by DWMH and JCWMH, which accounted for 49.1 and 47.5%, respectively. CONCLUSION: This study indicates that nutritional status and WMH are both closely associated with cognitive function in patients with CSVD. WMH mediated the association between malnutrition and cognitive impairment in the mediation model. These findings highlight WMH as a potential link between nutritional status and cognitive function, providing a clinically relevant perspective for understanding the association between malnutrition and cognitive impairment.