The efficiency of the brain connectome is associated with cerebrovascular reactivity in persons with white matter hyperintensities

Abstract

The purpose of this study was to determine the relationship between the organization of the brain connectome and cerebrovascular reactivity (CVR) in persons with white matter hyperintensities. Diffusion tensor and CVR mapping 3T MRI scans were acquired in 31 participants with white matter hyperintensities. In each participant, the connectome was assessed by reconstructing all white matter tracts with tractography and segmenting the whole brain into multiple regions. Graph theory analysis was performed to quantify how effectively tracts connected brain regions by measuring the global and local efficiency of the connectome. CVR in white matter and gray matter was correlated with the global and local efficiency of the connectome, while adjusting for age, gender, and gray matter volume. For comparison, white matter hyperintensity volume was also correlated with global and local efficiency. White matter CVR was positively correlated with the global efficiency (coefficient: 23.3, p = .005) and local efficiency (coefficient: 2850, p = .004) of the connectome. Gray matter CVR was positively correlated with the global efficiency (coefficient: 21.3, p < .001) and local efficiency (coefficient: 2670, p < .001) of the connectome. White matter hyperintensity volume was negatively correlated with global efficiency (coefficient: −0.0002, p = .003) and local efficiency (coefficient: −0.024, p = .003) of the connectome. The association between CVR and the brain connectome suggests that impaired cerebrovascular function may be part of the pathophysiology of the disruption of the brain connectome in persons with white matter hyperintensities.

Associations of white matter hyperintensities with networks of grey matter blood flow and volume in midlife adults: a CARDIA MRI substudy

“…The chosen regional network properties are reflective of the importance and influence of individual nodes within a network; in the context of CBF and GMV covariance, these network properties describe the extent to which individual brain regions connect (i.e., covary) with others as well as the impact of these connections on the overall network. The regional and widespread nature of these network alterations, therefore, could reflect subtle WMH-related physiological and structural changes beginning in early stages of disease, and may precede larger network-wide breakdown as reported in more severe stages of SVD (Frey et al, 2020;Lawrence et al, 2014Lawrence et al, , 2018Petersen et al, 2020;Reginold et al, 2019;Tuladhar et al, 2016;Xu et al, 2018). Similarly, deficits in regional brain physiology and structure are known to be associated with SVD severity as indexed by increasing WMH volume (Crane et al, 2015;Habes et al, 2016;C.…”

Decreased Cerebrovascular Reserve is the Initial Cause of White Matter Hyperintensity Related Cognitive Decline

“…In addition, it is reported that impaired CVR is the most reliable neuroimaging predictor of impending cerebrovascular disease [15,16], and could be a neuroimaging marker guiding the treatment and prevention of stroke and cerebral small vessel disease (CSVD) [17,18]. Furthermore, increasing evidences have demonstrated that CVR function is associated with subtle perfusion and microstructure changes in normal-appearing white matter (NAWM) [19], and has been involved in the pathophysiology disruption of the brain network connectome in individuals with WMH [20]. All these studies suggest that CVR might be an initial factor leading to WMH and cognitive decline.…”

“…Recently, rs-fMRI has been applied to explore CVR in cerebral large vessel diseases including carotid artery stenosis carotid or occlusion, Moyamoya disease [24,[27][28][29]. Furthermore, emerging studies used BOLD signal technology to evaluate CVR in WMH individuals and found that impaired CVR was associated with WMH [20,30,31]. However, all these studies didn't further explore whether impaired CVR can leads to cognitive decline through WMH.…”

Lower Cerebrovascular Reactivity Contributed to White Matter Hyperintensity‐Related Cognitive Impairment: A Resting‐State Functional MRI Study

“…There is growing recognition of the link between cerebrovascular dysfunction and WMH. Impaired cerebrovascular reactivity function has been associated with WMH lesions, 16,17 and normal‐appearing white matter (NAWM) regions progressed to WMH 18,19 cortical thinning, 20 subtle microstructural and perfusion changes 21 in NAWM, and has been involved in the disruption of local and global networks in the connectome 22 . All of these factors may result in CI.…”

“…Impaired cerebrovascular reactivity function has been associated with WMH lesions, 16,17 and normal-appearing white matter (NAWM) regions progressed to WMH 18,19 cortical thinning, 20 subtle microstructural and perfusion changes 21 in NAWM, and has been involved in the disruption of local and global networks in the connectome. 22 All of these factors may result in CI. Meanwhile, some previous studies have reported associations between CVR reductions and poor cognitive performance, although this relationship has been controversial.…”