Quantitative Electroencephalogram Indices With Inflammatory And Metabolic Risk Factors Are Associated With Nonmotor Dysfunctions In Parkinsonism

BackgroundQuantitative electroencephalography(QEEG),is a non-invasive,high temporal resolution,and objective diagnostic method that can provide a rapid evaluation of instantaneous neuronal and synaptic function and may be sensitive to early neurodegenerative changes.Several studies have suggested that QEEG features may distinguish dementia.Patients with Parkinson’s disease(PD)can develop cognitive impairment or dementia,interfering with activities of daily living and increases disease burden.Recent studies have showon that inflammation and lipid metabolism could influence the blood-brain barrier integrity and participate in the activation of synaptic loss,also be correlated with the EEG activity.Reliable objective markers for cognitive severity in PD with dementia(PDD)are needed.Parkinsonism plus syndromes(PPS),including progressive supranuclear palsy(PSP)and multiple system atrophy(MSA),shares similar motor and nonmotor symptoms,and is easily misdiagnosed as PD,especially in the early stage of the disease due to lacking diagnostic markers.To address current gaps in knowledge,we examined the associations between inflammation and lipid metabolism in PDD,and between QEEG features and the severity of cognition in PD.In addition,we characterize the patterns of QEEG and EEG functional connectivity(FC)that can differentiate patients with PD from those with PSP and MSA.Objective1.We investigated if QEEG indices can differentiate PD with nondementia(PDND)from PDD,and to determine if QEEG indices correlate with inflammation and lipid metabolism markers in PD.2.We characterized the patterns of QEEG and EEG-FC that differentiate PD from PSP or MSA,and explore the correlation between the differential QEEG indices and nonmotor dysfunctions in PD and MSA/PSP.Methods1.A total of 125 individuals comprising of 31 PDD,47 patients with PD-ND and 47 healthy controls were included.We calculated the absolute spectral power(ASP)of frequency bands and the slow-to-fast frequency ratios of specific brain regions.Comparisons of plasma markers between the PDD group and the PD-ND group were measured.We performed binary logistic regression to explore the potential risk factors in patients with PDD and PD-ND.Correlation among QEEG indices,disease severity,and plasma metabolic and inflammatory markers are demonstrated.We then performed receiver operator characteristic(ROC)curve analysis to measure the sensitivity and specificity of the QEEG indices and laboratory markers to predict PDD.2.We enrolled 52 patients with PD,31 with MSA,22 with PSP,and 50 agematched health controls to compare QEEG indices among specific brain regions.Oneway analysis of variance was applied to assess QEEG indices between groups;Spearman’s correlations were used to examine the relationship between QEEG indices and nonmotor symptoms scale(NMSS)and mini-mental state examination(MMSE).FCs using weighted phase lag index(wPLI)were compared between patients with PD and those with MSA/PSP.Results1.In our study,we demonstrated that decreased high-density lipoprotein cholesterol(HDL-C),and increased hypersensitive C-reactive protein(Hs-CRP)were correlated with PDD but not for PD-ND,We found that a significantly higher global ASP of delta frequency and global SPR in PDDs than in patients with PD-ND and HCs,especially in the frontal brain region.Moreover,a significantly lower occipital alpha peak frequency was found in PDD.However,no significant differences in QEEG indices were found between patients with PD-ND and We also found that EEG slowing showed a negative correlation with superoxide dismutase(SOD)but a positive correlation with HDL-C and Hs-CRP.Our ROC curve analysis results show that QEEG indices,HDL-C and Hs-CRP have appropriate sensitivity and specificity in distinguishing patients with PDD and those with PD-ND,adjusted with age.2.Patients with PSP revealed higher scores on the NMSS and lower MMSE scores than those with PD and MSA,with similar disease duration.The delta and theta powers revealed a significant increase in PSP,followed by PD and MSA.Patients with PD presented a significantly lower slow-to-fast ratio than those with PSP in the frontal region,while patients with PD presented significantly higher EEG-slowing indices than patients with MSA.The frontal slow-to-fast ratio showed a negative correlation with MMSE scores in patients with PD and PSP,and a positive correlation with NMSS in the perception and mood domain in patients with PSP but not in those with PD.Compared to PD,MSA presented enhanced FC in theta and delta bands in the posterior region,while PSP revealed decreased FC in the delta band within the frontal-temporal cortex.Conclusions1.QEEG indices,combined with HDL-C and Hs-CRP are potentially useful for the evaluation of PDD.Our current findings suggest that peripheral inflammation might contribute to the pathogenesis of cognitive impairment and EEG slowing in PDD.2.These findings suggest that QEEG might be a useful tool for evaluating the nonmotor dysfunctions in PD and AP.Our QEEG results suggested that with similar disease duration,the cortical neurodegenerative process was likely exacerbated in patients with PSP,followed by those with PD,and lastly in patients with MSA.