帕金森病非运动症状与纹状体囊泡单胺转运蛋白2密度的相关性

目的探讨帕金森病(PD)患者非运动症状(NMSs)和纹状体部位的囊泡单胺转运蛋白2(VMAT2)密度之间的相关性。方法2018年12月至2019年12月从中山大学附属第一医院共前瞻性招募29名健康受试者男16名,女13名,年龄(48.8±14.2)岁]和67例PD患者,PD患者包括31例改良Hoehn-Yahr(mH-Y)Ⅱ期患者男16例,女15例,年龄(53.4±8.5岁)]、36例mH-YⅢ期患者男19例,女17例,年龄(63.1±8.2岁)]。所有受试者均行18F-氟丙基-(+)-二氢丁苯那嗪18F-FP-(+)-DTBZ,18F-AV133]PET/CT检查,以枕叶皮质为参照区,测定纹状体各亚区的特异性摄取比值(SURs)。PD患者的NMSs通过临床量表进行评估。组间参数比较采用两独立样本t检验、单因素方差分析(最小显著差异t检验),最后通过Pearson相关分析和多元逐步回归分析来评估纹状体SURs与临床NMSs之间的相关性。结果NMSs统计结果发现,改良mH-YⅡ、Ⅲ期PD患者之间抑郁(3.51±1.34)与(11.36±3.87)分]、焦虑(2.35±1.45)与(6.00±3.32)分]、睡眠障碍(132.90±12.26)与(110.34±19.69)分]及生活质量(7.58±3.37)与(24.01±10.15)分]评分差异有统计学意义(t值:-10.573~5.439,均P<0.05),但2组间认知评分差异无统计学意义(t=1.067,P>0.05)。健康受试者纹状体SURs为1.28±0.22,mH-YⅡ期与Ⅲ期患者纹状体SURs分别为0.65±0.16和0.31±0.14,3组间差异有统计学意义(F=83.11,P<0.05),mH-YⅡ期与Ⅲ期两两比较差异也有统计学意义(t=9.116,P<0.05)。除认知评分外,PD患者NMSs其余评分均与纹状体SURs相关(r值:-0.647~-0.426,均P<0.05)。回归分析结果表明,总纹状体SURs是预测帕金森病睡眠量表(PDSS)及PD非运动症状量表(NMSS)评分的最佳变量(R2值:0.234、0.378,均P<0.001),对侧尾状核SURs是预测汉密尔顿抑郁评定量表(HAMD)评分(R2=0.402,P<0.001)的最佳变量,对侧壳核的SURs是预测汉密尔顿焦虑评定量表(HAMA)评分(R2=0.204,P<0.001)的最佳变量。结论PD患者纹状体VMAT2减少与NMSs之间具有相关性,提示多巴胺供应减少可能在PD发展过程中发挥了重要作用。

Correlation between striatal vesicular monoamine transporter 2 and the non-motor symptoms in Parkinson′s disease

Objective To explore the relationship between vesicular monoamine transporter 2(VMAT2)density in the striatum and the non-motor symptoms(NMSs)in patients with Parkinson′s disease(PD).Methods From December 2018 to December 2019,29 normal controls(16 males,13 females,age:(48.8±14.2)years),31 patients with PD at the Hoehn-Yahr(mH-Y)Ⅱstage(16 males,15 females,age:(53.4±8.5)years)and 36 patients with PD at mH-YⅢstage(19 males,17 females,age:(63.1±8.2)years)in the First Affiliated Hospital of Sun Yat-sen University were prospectively enrolled in this study.All subjects underwent 18F-fluoropropyl-(+)-dihydrotetrabenazine(18F-FP-(+)-DTBZ,18F-AV133)PET/CT imaging,then the specific uptake ratios(SURs)of striatal subregions were measured with the occipital cortex as the reference background region.The clinical data,laboratory data and imaging results were collected.The NMSs of each patient were evaluated with Hamilton Anxiety Rating Scale(HAMA),Hamilton Depression Rating Scale(HAMD),Parkinson′s Disease Sleep Scale(PDSS),Montreal Cognitive Assessment(MoCA),Parkinson′s Disease Quality of Life Questionnaire(PDQL)and Non-Motor Symptoms Scale(NMSS).The independent-sample t test and one-way analysis of variance(the least significant difference t test)were used to compare data differences.Finally,the association of the striatal SURs with the clinical symptom scores were evaluated with Pearson correlation analysis and multivariable stepwise regression analysis.Results Significant differences were found in depression(3.51±1.34 vs 11.36±3.87),anxiety(2.35±1.45 vs 6.00±3.32),sleep disorder(132.90±12.26 vs 110.34±19.69)and life quality(7.58±3.37 vs 24.01±10.15)scores between the mH-Y stageⅡand the stageⅢpatients(t values:from-10.573 to 5.439,all P<0.05),while cognitive scores did not differ significantly between the 2 PD groups(t=1.067,P>0.05).Compared with healthy control group(1.28±0.22),the PD groups displayed a more marked decrease of SURs in the bilateral putamen and in the caudate nucleus(0.65±0.16 and 0.31±0.14;F=83.11,P<0.05),and the SURs of patients at stageⅡwere higher than those of the patients at stageⅢ(t=9.116,P<0.05).NMSs scores of PD patients,with the exception of cognition scores,were correlated with striatal SURs(r values:from-0.647 to-0.426,all P<0.05).Regression analysis showed that total striatum SURs was the best predictor of PDSS and NMSS scores(R2 values:0.234,0.378,both P<0.001),while contralateral caudate nucleus SURs were best predictor of HAMD scores(R2=0.402,P<0.001).The SURs of contralateral putamen were best variables for predicting HAMA scores(R2=0.204,P<0.001).Conclusion The correlation between the decreased striatal VMAT2 and a broad spectrum of NMSs in patients with PD is established,suggesting that the defect in dopamine supply may be an early abnormality promoting mechanisms leading to the development of NMSs in PD.