Contribution of Inflammation and Hypoperfusion to White Matter Hyperintensities-Related Cognitive Impairment

Abstract

White matter hyperintensities (WMHs) of presumed vascular origin are one of the most important neuroimaging markers of cerebral small vessel disease (CSVD), which are closely associated with cognitive impairment. The aim of this study was to elucidate the pathogenesis of WMHs from the perspective of inflammation and hypoperfusion mechanisms. A total of 65 patients with WMHs and 65 healthy controls were enrolled in this study. Inflammatory markers measurements [hypersensitive C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2)], cognitive evaluation, and pseudocontinuous arterial spin labeling (PCASL) MRI scanning were performed in all the subjects. The multivariate logistic regression analysis showed that Lp-PLA2 was an independent risk factor for WMHs. Cerebral blood flow (CBF) in the whole brain, gray matter (GM), white matter (WM), left orbital medial frontal gyrus [MFG.L (orbital part)], left middle temporal gyrus (MTG.L), and right thalamus (Tha.R) in the patients was lower than those in the controls and CBF in the left triangular inferior frontal gyrus [IFG.L (triangular part)] was higher in the patients than in the controls. There was a significant correlation between Lp-PLA2 levels and CBF in the whole brain (R = −0.417, p < 0.001) and GM (R = −0.278, p = 0.025), but not in the WM in the patients. Moreover, CBF in the MFG.L (orbital part) and the Tha.R was, respectively, negatively associated with the trail making test (TMT) and the Stroop color word test (SCWT), suggesting the higher CBF, the better executive function. The CBF in the IFG.L (triangular part) was negatively correlated with attention scores in the Cambridge Cognitive Examination-Chinese Version (CAMCOG-C) subitems (R = −0.288, p = 0.020). Our results revealed the vascular inflammation roles in WMHs, which may through the regulation of CBF in the whole brain and GM. Additionally, CBF changes in different brain regions may imply a potential role in the modulation of cognitive function in different domains.

Contrast‐agent‐free state‐of‐the‐art MRI on cerebral small vessel disease—part 1. ASL, IVIM, and CVR

“…Perfusion abnormalities are a common finding in cSVD, with evidence suggesting that CBF and cSVD severity are negatively associated 7,20 . Also, CBF changes have been associated with inflammation in GM and impaired cognitive function in different domains 21 . However, it remains unclear whether reduced CBF is consequential or contributes to the severity of white matter hyperintensities (WMHs) observed in fluid‐attenuated inversion recovery (FLAIR) or T 2 ‐weighted MRI, which emphasizes the need for longitudinal studies to address this issue further.…”

Association of Sleep Duration and Change Over Time With Imaging Biomarkers of Cerebrovascular, Amyloid, Tau, and Neurodegenerative Pathology

“…It remains unclear however how longer sleep duration may promote vascular pathology. Cerebrovascular neuroimaging biomarkers are closely linked to neuroinflammatory processes, 39,40 which are also of great significance in the development of AD. Long sleep duration was previously shown to associate with elevated inflammatory levels.…”

Higher serum Lp-PLA2 is associated with cognitive impairment in Parkinson’s disease patients

“…However, a recent study supports the opposite conclusion. Huang et al also proposed that Lp-PLA2 was an independent risk factor for WMHs, but the level of Lp-PLA2 mass was significantly higher in cognitively impaired CSVD patients than in cognitively normal controls ( Huang et al, 2021 ). Currently, increasing evidence suggest that higher levels of Lp-PLA2 are risk factors for cognitive impairment.…”