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The effect of deep medullary veins disruption on cognitive function is mediated by microstructure integrity in patients with cerebral small vessel disease1Radiology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China, 2Neurology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China
Synopsis
We aimed to evaluate the effect of deep medullary veins (DMVs) disruption on cognition in cerebral small vessel disease (cSVD) patients and to examine whether white matter microstructure integrity mediate the relationship between DMVs disruption and cognitive impairment. Susceptibility-weighted images were used to observe characteristics of DMVs. White matter was classified into white matter hyperintensities (WMH) and normal appearing white matter (NAWM), and the average Fractional anisotropy (FA) and cerebral blood flow values of each region were extracted and compared. Mediation analyses revealed that the effect of DMVs score on cognition was mediated by microstructure integrity (FA value) in NAWM.
Introduction
Cerebral small vessel disease (cSVD) is a major cause of cognitive decline and dementia, and it is associated with pathological processes affecting arterioles, capillaries, and venules.1 However, in the context of cSVD and cognitive impairment, most studies focused on arteries changes, and only a few studies have concentrated on veins. Deep medullary veins (DMVs) disruption, which is a newly recognized cSVD imaging marker,2 plays a role in the pathogenesis of cSVD.3 Previous studies have found that the tortuosity of DMVs increased in patients with Alzheimer’s disease and mild cognitive impairment compared to controls, suggesting that DMVs disruption might be involved in the process of cognitive decline.4 In addition, DMVs disruption may not directly lead to cognitive impairment, but plays a role through the changes of white matter microstructure in its drainage area or affecting metabolic activity by causing venous ischemia.3 Therefore, in this study, we aimed to evaluate the effect of DMVs disruption on cognition in cSVD patients and to examine whether white matter microstructure integrity and cerebral blood flow (CBF) mediate the relationship between DMVs disruption and cognitive impairment.Methods
We retrospectively reviewed the clinical, laboratory and imaging data of cSVD patients prospectively collected in our center from April 2014 to June 2017. Susceptibility-weighted images (SWI) were used to observe characteristics of DMVs and derived a brain region-based DMVs visual score according to previous study.2 CBF maps were derived from Arterial spin labeling (ASL) perfusion MRI. Fractional anisotropy (FA) map were derived from diffusion-tensor imaging (DTI). White matter was classified into WMH and normal appearing white matter (NAWM), and the average FA and CBF values of each region were extracted and compared. Mini-Mental State Examination (MMSE) and Montreal cognitive assessment (Montreal Cognitive Assessment) were used to evaluate the cognitive function. The relationship between DMVs disruption, white matter microstructure and cognitive functions was analyzed by multiple mediation analyses.Results
59 cSVD patients were included. DMVs score was significantly correlated with FA value (Pearson r=-0.464, p＜0.001) in NAWM (Figure 1). DMVs score and FA value in WMH, CBF in WMH, CBF in NAWM were not significantly correlated. After adjusting for age and years of education, mediation analyses revealed that the effect of DMVs score on MMSE and MoCA score was mediated by FA in NAWM (Figure 2). Figure 3 was an example for correlation between DMVs scores, FA value and cognition.Discussion
Our studies demonstrated that DMVs affected cognitive function by affecting NAWM microstructure integrity. Pathological studies showed that DMVs disruption in cSVD patients was often accompanied by demyelination and axonal loss in the same area.5 DMVs disruption might increase vascular resistance, leading to compromising interstitial fluid circulation which resulting in accumulation of toxic substances, and finally cause white matter microstructural damage.6 Loss of white matter integrity can affect the communication between different cortical regions, and further lead to cognitive impairment.7Conclusion
Our results provided a new perspective on venous involvement in cognitive impairment, which may open new avenues for treating cognitive decline in cSVD patients.Acknowledgements
No acknowledgement found.References
1. Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. The Lancet. Neurology. 2013;12:822-838
2. Zhang R, Zhou Y, Yan S, et al. A brain region-based deep medullary veins visual score on susceptibility weighted imaging. Frontiers in aging neuroscience. 2017;9:269
3. Keith J, Gao FQ, Noor R, et al. Collagenosis of the deep medullary veins: An underrecognized pathologic correlate of white matter hyperintensities and periventricular infarction? Journal of neuropathology and experimental neurology. 2017;76:299-312
4. Bouvy WH, Kuijf HJ, Zwanenburg JJ, et al. Abnormalities of cerebral deep medullary veins on 7 tesla mri in amnestic mild cognitive impairment and early alzheimer's disease: A pilot study. Journal of Alzheimer's disease : JAD. 2017;57:705-710
5. Black S, Gao F, Bilbao J. Understanding white matter disease: Imaging-pathological correlations in vascular cognitive impairment. Stroke. 2009;40:S48-52
6. Yan S, Wan J, Zhang X, et al. Increased visibility of deep medullary veins in leukoaraiosis: A 3-t mri study. Frontiers in aging neuroscience. 2014;6:144
7. Vernooij MW, Ikram MA, Vrooman HA, et al. White matter microstructural integrity and cognitive function in a general elderly population. Archives of general psychiatry. 2009;66:545-553
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