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Use of Vitamin K Antagonists and Brain Morphological Changes in Older Adults: An Exposed/Unexposed Voxel-Based Morphometric Study

Background: Vitamin K antagonists (VKAs) are commonly used for their role in haemostasis by interfering with the vitamin K cycle. Since vitamin K also participates in brain physiology, this voxel-based morphometric study aimed to determine whether the duration of exposure to VKAs correlated with focal brain volume reduction in older adults. Methods: In this exposed/unexposed (1: 2) study nested within the GAIT (Gait and Alzheimer Interactions Tracking) cohort, 18 participants exposed to VKA (mean age 75 ± 5 years; 33.3% female; mean exposure 2,122 ± 1,799 days) and 36 matched participants using no VKA (mean age 75 ± 5 years; 33.3% female) underwent MRI scanning of the brain. Cortical grey and white matter volumes were automatically segmented using statistical parametric mapping. Age, gender, educational level, history of atrial fibrillation, type of MRI, and total intracranial volume were included as covariables. Results: The duration of exposure to VKA correlated inversely across the whole brain with the subvolumes of two clusters in the grey matter (right frontal inferior operculum and right precuneus) and one cluster in the white matter (left middle frontal gyrus). In contrast, the grade of white matter hyperintensities did not differ according to the use of VKA. Conclusion: We found focal atrophies in older adults exposed to VKA. These findings provide new insights elucidating the effects of VKAs on brain health and function in older adults.