| Part 1 A cross-sectional study on the relationship between glymphatic function and white matter hyperintensities in patients with cerebral small vessel diseaseObjective:To determine the relationship between brain glymphatic function and the volume of white matter hyperintensities(WMH)in patients with small vessel disease(cSVD).Methods:We retrospectively reviewed the clinical and imaging data of cSVD patients prospectively collected in our center from January 2010 to December 2020.All patients underwent three-dimensional T1-weighted imaging(3D-T1),T2 fluid-attenuated inversion recovery(Flair),susceptibility weighted imaging(SWI),and diffusion tensor imaging(DTI).Glymphatic function was defined as ALPS-index,which was calculated from SWI and DTI.Flair images were used to calculate WMH volume.The presence and number of lacunes and microbleeds were recorded.Pearson’s correlation analysis and linear regression analysis were used to examine the association between the ALPS-index and WMH volume.Results:A total of 724 patients with cSVD were included,with an average age of 61.76 ±9.46 years and 348(48.1%)females.The average volume of WMH was 20.72 ± 26.83 ml.206(28.5%)patients presented with lacunes and 202(27.9%)patients presented with microbleeds.After adjusting for gender,drinking,hypertension and diabetes,age was independently associated with ALPS-index(P < 0.001).Univariate analysis showed that patients with higher WMH volume had greater age,higher proportion of hypertension,severer microbleeds and lacunes and lower ALPS-index(all P<0.05).Multiple linear regression analysis showed lower ALPS-index was independently associated with higher WMH volume(all P<0.001),after adjusting for age,drinking,hypertension and presence of lacunes or presence of microbleeds or number of lacunes or number of microbleeds.Conclusions:The brain glymphatic clearance function decreased with ageing;Glymphatic function is associated with white matter hyperintensities in patients with small vessel disease.Part 2 Longitudinal study on the relationship between brain glymphatic function and white matter hyperintensities progression and cognitive functionⅠ Effects of brain glymphatic function on the progression of white matter hyperintensitiesObjective:To determine the relationship between brain glymphatic function and the progression of WMH in patients with cSVD.Methods:We retrospectively reviewed the clinical and imaging data of cSVD patients prospectively collected in our center from January 2010 to December 2020.All patients underwent baseline and 1.5 years follow up 3D-T1,T2 Flair,SWI and DTI.Glymphatic function was defined as ALPS-index,which was calculated from SWI and DTI.Flair images were used to calculate WMH volume.The presence and number of lacunes and microbleeds were recorded.WMH progression was defined as higher WMH volume at review than baseline.Results:Totally,we included 201 cSVD patients,with an average age of 63.09 ± 9.39 years and 94(46.8%)females.Average interval from baseline to review was 16.3 ± 7.0months.140(69.6%)patients showed WMH progression.Univariate analysis showed that lower baseline ALPS-index was significantly associated with WMH progression(with progression vs without progression 1.34 ± 0.15 vs 1.45 ± 0.13,P<0.001).Baseline ALPS-index was independently associated with WMH progression(all P<0.05),after adjusting for age,baseline WMH volume or lacunes or microbleeds.Baseline WMH volume was not associated with follow up ALPS-index(P>0.05).Conclusion:Glymphatic function was associated with the progression of WMH in patients with cSVD.Ⅱ Effects of white matter hyperintensities progression on the cognitive declineObjective:To determine the relationship between the progression of WMH and cognitive decline in patients with cSVD.Methods:Patients with cSVD who underwent baseline and 1.5 years follow-up 3D-T1,T2 Flair,SWI,DTI and cognitive function assessment were prospectively enrolled in our center from January 2010 to December 2020.Glymphatic function was defined as ALPS-index,which was calculated from SWI and DTI.The cognitive function was assessed by mini-mental state examination(MMSE).WMH progression rate was defined as the ratio of volume change to time interval.Cognitive decline was defined as decrease of ≥2 points in the MMSE score between evaluations.Results:We included 164 cSVD patients in total,with an average age of 62.47 ± 9.42 years and 72(46.8%)females.Average WMH progression rate was 0.18 ± 0.24 ml per month.51(31.1%)patients presented cognitive decline.Baseline WMH volume was significantly associated with baseline MMSE score(Pearson r=-0.226,P=0.002).Baseline WMH volume was independently associated with baseline MMSE score,after adjusting for age and education(P<0.05).Univariate analysis showed that WMH progression rate was significantly higher in patients with cognitive decline than without(0.21 ± 0.27 vs 0.16 ± 0.22,P=0.011).WMH progression rate was independently associated with cognitive decline,after adjusting for age,education and baseline WMH volume(P<0.05).Conclusion:WMH progression was associated with cognitive decline in patients with cSVD.Part 3 Study on the mechanism of brain glymphatic function promoting the progression of white matter hyperintensitiesObjective:To explore the relationship between the enlarged perivascular space and the influence of glymphatic function on the progression of white matter hyperintensities in patients with cSVD.Methods:Patients with cSVD who underwent baseline and 1.5 years follow-up 3D-T1,T2-weighted imaging,Flair,SWI and DTI were prospectively enrolled in our center from January 2010 to December 2020.Glymphatic function was defined as ALPS-index,which was calculated from SWI and DTI.Flair images were used to calculate WMH volume.The presence and number of lacunes and microbleeds were recorded.WMH progression rate was defined as the ratio of volume change to time interval.Enlarged perivascular space(EPVS)in basal ganglia and centrum semiovale were assessed by semi quantitative scoring separately.Results:We included 170 cSVD patients in total,with an average age of 62.69 ± 9.26 years and 77(45.3%)females.Lower ALPS-index was independently related to severer EPVS in basal ganglia(all P <0.05),but not in centrum semiovale(all P >0.05),after adjusting for age,gender,WMH volume or lacunes or microbleeds.Severer enlarged perivascular space in basal ganglia was significantly correlated with higher rate of WMH progression(all P <0.05),after adjusting for age,ALPS-index,baseline WMH volume or number of lacunes or number of microbleeds.The β values of ALPS-index decreased after adjusting for the enlarged perivascular space in basal ganglia in the multivariate analysis for WMH progression,compared with exclusion of the enlarged perivascular space in basal ganglia.Conclusion:Enlarged perivascular space in the basal ganglia may mediate the effect of brain glymphatic function on the progression of white matter hyperintensities in patients with cSVD,that is,decreased glymphatic function promoted the increase of enlarged perivascular space in the basal ganglia,leading to the progression of white matter hyperintensities. |
PDF Full Text Request