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

Abstract

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.

The Relationships Between Vitamin K and Cognition: A Review of Current Evidence

“…Brangier et al analyzed the brain volume, using 3 or 1.5 Tesla MRI, of 54 subjects (18 under VKAs treatment and 36 matched controls) and found a significant inverse correlation between the duration of drug exposure and gray/white matter volume in the right frontal inferior operculum, right precuneus, and left middle frontal gyrus (71). The same author found an important decline in executive functions (assessed with frontal assessment battery) among geriatric patients treated with VKAs over at 24 months follow up.…”

Intracranial calcifications under vitamin K antagonists or direct oral anticoagulants: Results from the French VIKING study in older adults

“…Also in older adults, smaller whole-brain volume has been reported among those taking VKA regulary 9 compared to those taking no anticoagulant [7]. Specifically, the exposure to VKA correlated in another study with focal atrophies within the frontal lobes [8]. All these previous studies have yet addressed the brain changes only in terms of cerebral atrophy.…”

“…In fact, the use of VKA in animals has been associated with cognitive impairment and a dysregulation of the synthesis of sphingolipids, a constituent of the myelin sheath and neuronal membrane [6], and a reduction of the biological activation of the vitamin K-dependent proteins involved in neuronal physiology and survival [5]. Such changes may account for the onset of pathological morphological brain changes in VKA users [7,8].…”

Vitamin K2 in Health and Disease: A Clinical Perspective

“…Again, no significant association with MMSE scores was seen [ 123 ]. The same research group performed another study of brain morphological changes in patients taking VKAs and observed focal atrophies in older adults exposed to VKAs (18 community-dwellers), compared to 36 matched controls [ 124 ]. Annweiler et al further showed that fluindione treatment specifically caused more frequent cognitive impairment among 267 geriatric patients (56.9% female; mean age 83.4 ± 8.1 years) [ 125 ].…”