The Study On Cerebrospinal Fluid Biomarkers Of Parkinson’s Disease With Mild Cognitive Impairment

BACKGROUDParkinson’s disease(PD)cognitive impairment include PD with mild cognitive impairment(PD-MCI)and Parkinson’s disease dementia(PDD).With the development of Parkinson’s disease,mild cognitive impairment in Parkinson’s disease will progress to PDD.Therefore,early recognition of PD-MCI is very important for the treatment of Parkinson’s disease with cognitive impairment.However,biomarkers for the diagnosis of PD-MCI are lacking.More and more pathological studies have found that Lewy bodies,amyloid and neurofibrillary tangles play a key role in the development of PD cognitive impairment.It is unclear whether combining cerebrospinal fluid(CSF)α-Syn,t-tau,p-tau181 and Aβ1-42 can improve the clinical value of the diagnosis of PD-MCI.OBJECTIVETo explore the clinical value of combination of CSF α-Syn,p-tau181,t-tau and Aβ1-42 as biomarkers for the diagnosis of PD-MCI,and to provide more powerful auxiliary diagnosis and objective basis for the clinical diagnosis of PD-MCI.METHODSA total of 53 PD patients who were hospitalized and outpatients in neurology from August 2018 to September 2019 were collected.The clinical data such as age,sex,course of disease,MDS-UPDRS III,the classification of H&Y,MMSE,MoCA,HAMA and HAMD were collected.For each patient with Parkinson’s disease,a combination of comprehensive cognitive assessment and assessment of five cognitive domains were used.According to the Level-Ⅱ level in the diagnostic criteria for PD-MCI as published by Movement Disorder Society,all non-dementia patients with Parkinson’s disease were divided into two groups:PD-NC group(27 cases)and PD-MCI group(26 cases).And healthy controls group(HC)were collected(24 cases).CSF of all PD patients and healthy controls were collected.The levels of-Syn,t-tau,p-tau181 and Aβ1-42 protein in CSF of all PD patients and HC were detected by ELISA.The differences in protein levels between the groups were compared,and their correlation with cognition was analyzed.The area under the curve for the diagnosis of PD-MCI was calculated based on the ROC curve.RESULTSThere was had no statistical significance in clinical data such as age,sex,education level between HC vs PD-NC vs PD-MCI group.PD vs PD-MCI had no statistical significance in course of disease,H&Y grade,HAMA and HAMD(P>0.05).PD-MCI had higher MDS-UPDRS III score than PD-NC group(P<0.05).The overall cognitive function assessment showed that the scores of MMSE were lower than PD-NC group(P=0.001),MoCA in the PD-MCI group were significantly lower than those in the PD-NC and HC group(P<0.001).T-tau in The PD-MCI group was significantly higher than the PD-NC and HC groups(P=0.013).T-tau/p-tau181 was significantly higher in the PD-MCI group than in the PD-NC and HC groups(P<0.001).The increase of t-tau/p-tau181 level in CSF of PD correlates with the Block design test score(P=0.028)and Animal fluency test(P=0.017).The area under the ROC curve of t-tau protein to identified PD-MCI was 0.670(P=0.015),and the sensitivity and specificity were 69.2%and 56.9%,respectively.The area under the ROC curve of the t-tau/p-tau181 ratio to identify PD-MCI is 0.768(P<0.001),it’s sensitivity and specificity were 80.8%and 68.6%,respectively.CONCLUSIONThe increase in cerebrospinal fluid t-tau/p-tau181 in PD patients is related to their visuospatial function and executive functions.T-tau/p-tau181 may be used as a biomarker for the diagnosis of PD-MCI.