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This study aimed to investigate the mechanism and effective indicators to predict WMH\u2010related cognitive impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited 22 healthy controls (HC), 25 cases of WMH with normal cognition (WMH\u2010NC), and 23 cases of WMH with mild cognitive impairment (WMH\u2010MCI). 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\u2010related cognitive impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our study found that mean diffusivity (MD) values of several fiber bundles including the bilateral anterior thalamic radiation (ATR), the left inferior fronto\u2010occipital 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\u2010MCI 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Changes in the properties of DTI may be the potential mechanism of WMH\u2010related MCI, especially the right IFOF and the right ILF, which may become imaging markers for predicting WMH\u2010related cognitive dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13283","type":"journal-article","created":{"date-parts":[[2020,1,4]],"date-time":"2020-01-04T12:40:51Z","timestamp":1578141651000},"page":"576-588","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":111,"title":["Microstructural disruption of the right inferior fronto\u2010occipital and inferior longitudinal fasciculus 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