Associations of inferior frontal sulcal hyperintensities on brain MRI with cerebral small vessel disease, cognitive function, and depression symptoms.

Inferior frontal sulcal hyperintensities (IFSH) observed on fluid-attenuated inversion recovery (FLAIR) MRI have been proposed as indicators of elevated cerebrospinal fluid waste accumulation in cerebral small vessel disease (CSVD). However, to validate IFSH as a reliable imaging biomarker, further replication studies are required. The objective of this study was to investigate associations between IFSH and CSVD, and their potential repercussions, i.e., cognitive impairment and depression. We prospectively recruited 47 patients with CSVD and 29 cognitively normal controls (NC). IFSH were rated visually based on FLAIR MRI. Using different regression models, we explored the relationship between IFSH, group status (CSVD vs. NC), CSVD severity assessed with MRI, cognitive function, and symptoms of depression. Patients with CSVD were more likely to have higher IFSH scores compared to NC (OR 5.64, 95% CI 1.91-16.60), and greater CSVD severity on MRI predicted more severe IFSH (OR 1.47, 95% CI 1.14-1.88). Higher IFSH scores were associated with lower cognitive function (-0.96, 95% CI -1.81 to -0.10), and higher levels of depression (0.33, 95% CI 0.01-0.65). CSVD and IFSH may be tightly linked to each other, and the accumulation of waste products, indicated by IFSH, could have detrimental effects on cognitive function and symptoms of depression.