Inferior Frontal Sulcal Hyperintensity on FLAIR is Associated with Small Vessel Disease but not Alzheimer’s Pathology

Abstract

Background: The inferior frontal sulci are essential sites on the route of cerebrospinal fluid outflow. A recent study suggests that inferior frontal sulcal hyperintensities (IFSH) on FLAIR images might be related to glymphatic dysfunction. Objective: To investigate whether IFSH is associated with Alzheimer’s disease (AD) pathology and cerebral small vessel disease (SVD) burden. Methods: We retrospectively collected data from 272 non-demented subjects in the ADNI3 database. The IFSH was assessed on 3D fluid-attenuated inversion recovery images. The standardized uptake value ratios of amyloid and tau PET were used to reflect the AD pathology burden. To measure the SVD burden, we assessed white matter hyperintensities (WMH), dilation of perivascular spaces, microbleeds, and lacunes. Finally, we performed ordinal logistic regression analyses to investigate the associations between the IFSH score and AD pathology and SVD burden. Results: The IFSH score was associated with the deep WMH score (OR, 1.79; 95% CI, 1.24 – 2.59) controlling for age and sex. The association remained significant in the multivariable regression models. There was no association between the IFSH score and AD pathology burden. Conclusion: This study suggests that the IFSH sign is associated with SVD but not AD pathology. Further studies are needed to confirm the findings.