Altered Inflammation And Perfusion To White Matter Hyperintensity Of Presumed Vascular Origin-related Cognitive Impairment

Objective White matter hyperintensity（WMH）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 intricate etiology and pathogenesis of WMH have been extensively studied in recent studies.To date,studies examining WMH from the perspective of multiple mechanisms are lacking.The aim of this study was to elucidate the pathogenesis of WMH from the perspective of altered inflammation and perfusion.Methods 65 patients with confirmed WMH from the outpatient department or ward of the Department of Neurology,First Affiliated Hospital of Anhui Medical University between June 2020 and June 2021 were enrolled in our study.Meanwhile,another 65 healthy controls（HCs）were selected as controls.General information collection;cognitive evaluation,such as Cambridge Cognitive Examination-Chinese Version（CAMCOG-C）,Mini-Mental State Examination（MMSE）,Montreal Cognitive Assessment（Mo CA）,Stroop Color Word Test（SCWT）,Trail Making Test（TMT）and so on;inflammatory markers measurement,including hypersensitive C-reactive protein（hs CRP）and lipoprotein-associated phospholipase A2（Lp-PLA2）;and Pseudo-Continuous Arterial Spin Labeling（p CASL）Magnetic Resonance Imaging（MRI）scanning were performed in all subjects.The multivariate logistic regression analysis was used to investigate the important risk factors for WMH.Based on the analysis of ASL data,regions with differing perfusion were extracted as regions of interest（ROIs）for further correlation analysis.The correlation analysis between plasma Lp-PLA2 levels and CBF in whole brain,gray matter（GM）,and white matter（WM）were analyzed.Besides,correlation between CBF in ROIs and neuropsychological tests were conducted in patients with WMH.Results We noted significant differences in the Lp-PLA2 levels（P = 0.022）between patients with WMH and HCs.There were no significant differences in the hs CRP levels.Compared with the HCs,patients with WMH have impaired cognitive functions in domains of total cognitive,attention,and executive function.The multivariate logistic regression analysis showed that hypertension and Lp-PLA2 were important risk factors for WMH.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 were 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（P <0.05）.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.In addition,CBF in MFG.L（orbital part）were positively associated with total CAMCOG-C（r = 0.414,P < 0.001）,execution function in CAMCOG-C subitems（r = 0.444,P < 0.001）,and negatively associated with TMT A（r =-0.437,P < 0.001）and TMT B scores（r =-0.431,P < 0.001）in the patients.There was a negatively correlation between CBF in Tha.R and Stroop-C scores（r =-0.426,P < 0.001）.There was also a correlation between CBF in IFG.L（triangular part）and attention scores in CAMCOG-C subitems（r =-0.288,P = 0.020）.However,there was no significant correlation between CBF in MTG.L and neuropsychological test results.Conclusion Our results revealed the role of vascular inflammation in WMH,which may through the regulation of CBF in the whole brain and GM.Additionally,CBF alteration in different brain regions may imply potential roles in the modulation of cognitive function in different domains.