Abnormal Cerebral Blood Flow and Functional Connectivity Strength in Subjects With White Matter Hyperintensities

Abstract

White matter hyperintensities (WMHs) are common neuroimaging findings in the aging population and are associated with various clinical symptoms, especially cognitive impairment. Abnormal global cerebral blood flow (CBF) and specific functional connections have been reported in subjects with higher WMH loads. Nevertheless, the comprehensive functional mechanisms underlying WMH are yet to be established. In this study, by combining resting-state functional magnetic resonance imaging and arterial spin labeling, we investigated the neurovascular dysfunction in subjects with WMH in CBF, functional connectivity strength (FCS), and CBF–FCS coupling. The whole-brain alterations of all these measures were explored among non-dementia subjects with different WMH loads using a fine-grained Human Brainnetome Atlas. In addition, exploratory mediation analyses were conducted to further determine the relationships between these neuroimaging indicators, WMH load, and cognition. The results showed that subjects with higher WMH loads displayed decreased CBF and FCS mainly in regions involving the cognitive- and emotional-related brain networks, including the default mode network, salience network, and central executive network. Notably, subjects with higher WMH loads also showed an abnormal regional CBF–FCS coupling in several regions of the thalamus, posterior cingulate cortex, and parahippocampal gyrus involving the default mode network. Furthermore, regional CBF in the right inferior temporal gyrus and right dorsal caudate may mediate the relationship between WMH load and cognition in WMH subjects. These findings indicated characteristic changes in cerebral blood supply, brain activity, and neurovascular coupling in regions involving specific brain networks with the development of WMH, providing further information on pathophysiology underpinnings of the WMH and related cognitive impairment.

Effect of Menopause Status on Brain Perfusion Hemodynamics

“…43,44 Furthermore, WMHs are usually accompanied by other damages in the brain, including cortical microinfarcts and cerebral microbleeds, which may lead to the lower blood supply required by global brain tissues. 39 In line with previous findings, our study suggested that although we did not include WMHs regions in the CBF calculation, the decreased CBF in women during menopause transition and after menopause transition may be largely due to the increased proportions of WMHs affecting the whole brain perfusion hemodynamics.…”

“…37 Previous studies have demonstrated decreased CBF and delayed arterial transit time associated with WMH. 30,[38][39][40] The underlying mechanisms may be that WMHs reflect white matter atrophy with fewer cells, or damage to the neural fiber and local blood vessels, which are associated with regional hypoperfusion. 41 A recent study has demonstrated an accelerated increase in WMH, and a higher burden of WMH in women after menopause, compared with premenopausal women and men of similar age, 42 which was in accordance with the higher proportions of WMHs in perimenopausal and postmenopausal groups in the current study.…”

Neurovascular coupling in patients with type 2 diabetes mellitus

“…In fact, while Lei et al (2021) were able to relate the DAN-DMN anti-correlation to the poor modulation of attentional processes in response to shifting cognitive demands, here we added the notion that such an unbalance in the neural resource management could be linked to defective NVC within and across the two networks, as discussed above. Thus, as far as future studies will confirm the neurovascular origin of this unbalance, it would be more than likely that these neural effects can occur in the earliest stages of cognitive decline, i.e., before the cognitive impairment becomes manifest at the clinical evaluation ( Gorelick et al, 2016 ; Cheng et al, 2021 ; Huang et al, 2021 ; Liu et al, 2021 ).…”

Research Progress on MRI for White Matter Hyperintensity of Presumed Vascular Origin and Cognitive Impairment

“…3D-ASL permits non-invasive quantification of CBF and has good reliability and repeatability ( 45 ). One study reported that greater WMH severity was associated with lower average CBF of whole-brain white matter and CBF at and around the lesion ( 42 , 46 ). A quantitative study of CBF in patients with different degrees of WMH using 3D-ASL revealed that CBF in WMH was lower than that in the surrounding tissues, and whole-brain CBF in patients with confluent WMH was 20% lower than that in patients with spotted or newly confluent WMH ( 47 ).…”