Relationship Between Freezing Of Gait In Parkinson’s Disease And Locus Coeruleus Dysfunction:A Neuromelanin MRI Study

Objective:We aim to investigate the relationship between Freezing of gait(FoG)in Parkinson’s disease(PD)and noradrenergic dysfunction caused by the locus coeruleus(LC)degeneration by analyzing LC signals in Neuromelanin magnetic resonance imaging(NM-MRI).Furthermore,this paper can provide a unique perspective to clarify the mechanism of FoG and find biomarkers that can be leveraged to guide clinically stratified treatment and medication.Methods:From March 2022 to December 2022,46 patients with primary PD who met the diagnostic criteria of the International Movement Disorder Society(MDS)in 2015 were collected as research subjects.PD patients were divided into PD FoG+group(n=22)and PD FoG-group(n=24).At the same time,13 healthy volunteers matched by sex and age were collected as health controls(HC).NM-MRI and routine head magnetic resonance imaging were performed on all subjects.The contrast to noise ratio(CNR)and the normalized CNR of all subjects’ bilateral LC were calculated.During the collection of clinical data,since the purpose of this study is to discuss whether the presence of FoG in PD patients will affect the CNR value after LC standardization,we have included all possible confounding factors according to previous studies,such as age,sex,course of disease,presence or absence of rapid eye movement sleep behavior disorder(RBD)and postural hypotension,Montreal cognitive assessment(Mo CA),The Hamilton depression scale(HAMD),apathy scale(AS)and the UPDRS-III part of the Unified Parkinson’s disease rating scale(UPDRS).Statistical methods mainly use two methods to construct linear regression models to control confounding factors.The construction method of model 1 is stepwise regression;The construction method of model 2 is to screen the confounding factors based on the change-in-estimate(CIE)method,and then use the multivariate linear regression model to correct the confounding factors.The criterion for determining the collinearity of the regression model is Variance inflation factor(VIF)>2,and the two independent variables are highly correlated,with correlation coefficient>0.7.Results:The statistical models showed that except for the target factor FoG(model 1: β: 0.127,95%CI: 0.019-0.236,P=0.023;Model 2: β: 0.153,95%CI: 0.019-0.287,P=0.026),REM sleep behavior disorder(RBD)(model 1: β: 0.182,95%CI: 0.073-0.291,P=0.002;Model 2: β: 0.171,95%CI: 0.048-0.294,P=0.008)and gender(model 1: β: 0.150,95%CI:0.042-0.257,P=0.007)were independent factors affecting the normalized CNR of the left LC.Among them,RBD had the greatest influence,followed by gender and presence or absence of FoG.Interpretation:The occurrence of FoG is associated with noradrenergic dysfunction caused by LC degeneration.