Microstructural disruption of the right inferior fronto‐occipital and inferior longitudinal fasciculus contributes to WMH‐related cognitive impairment

AIMS: White matter hyperintensity (WMH) is the most common neuroimaging manifestation of cerebral small vessel disease and is related to cognitive dysfunction or dementia. This study aimed to investigate the mechanism and effective indicators to predict WMH‐related cognitive impairment. METHODS: We recruited 22 healthy controls (HC), 25 cases of WMH with normal cognition (WMH‐NC), and 23 cases of WMH with mild cognitive impairment (WMH‐MCI). All individuals underwent diffusion tensor imaging (DTI) and a standardized neuropsychological assessment. Automated Fiber Quantification was used to extract altered DTI metrics between groups, and partial correlation was performed to assess the associations between WM integrity and cognitive performance. Furthermore, machine learning analyses were performed to determine underlying imaging markers of WMH‐related cognitive impairment. RESULTS: Our study found that mean diffusivity (MD) values of several fiber bundles including the bilateral anterior thalamic radiation (ATR), the left inferior fronto‐occipital fasciculus (IFOF), the right inferior longitudinal fasciculus (ILF), and the right superior longitudinal fasciculus (SLF) were negatively correlated with memory function, while that of the anterior component of the right IFOF and the posterior and intermediate component of the right ILF showed significant negative correlation with MMSE and episodic memory, respectively. Furthermore, machine learning analyses showed that the accuracy of recognizing WMH‐MCI patients from the WMH populations was up to 80.5% and the intermediate and posterior components of the right ILF and the anterior component of the right IFOF contribute the most. CONCLUSIONS: Changes in the properties of DTI may be the potential mechanism of WMH‐related MCI, especially the right IFOF and the right ILF, which may become imaging markers for predicting WMH‐related cognitive dysfunction.