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帕金森病(Parkinson disease,PD)作为第二大神经退行性疾病影响着全球约1%的60岁以上人群,其中约40%的患者会发展成为帕金森病痴呆(Parkinson disease dementia,PDD)。相比同龄健康者,PD患者发展成为PDD的风险高6倍[1]。而路易体痴呆(dementia with Lewy bodies,DLB)是仅次于阿尔茨海默病(Alzheimers disease, AD)的第二常见的神经变性性痴呆。DLB较PDD更为常见,二者在临床表现上均有PD综合征、痴呆、自主神经异常等症状。国际通用的临床鉴别方法通常依据“一年法则”,即认知损害,如先于PD症状或在其发作一年之内出现,通常诊断为DLB;若认知损害出现在PD确诊一年之后,则为PDD[2-3]。但因二者症状有较多相同之处,且部分患者临床症状不典型,症状演变常介于二者之间,诊断过程持续时间较长,不利于早期诊断、早期干预治疗,从而错过最佳治疗时期,临床实践中鉴别诊断的特异度低。DLB和PDD的病理特征均为路易体的形成,但β淀粉样蛋白(amyloid β-protein,Aβ)在脑组织中的沉积和脑脊液中Aβ蛋白、tau蛋白、丛生蛋白的水平也不同程度与这两种疾病有关。采用11C标记的匹兹堡化合物B(pittsburgh compound B,PIB)进行PET显像,可检测Aβ在脑内的分布情况。本研究通过分析PDD和DLB在11C-PIB PET/CT脑显像及脑脊液检测中存在的差异,旨在为临床提供对二者进行鉴别诊断的依据。
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表1列出了21例受试者的基本信息,包括性别、年龄、MMSE评分、PD症状持续时间及痴呆确诊持续时间。由表2可见,2组患者在年龄和MMSE评分方面差异无统计学意义。因临床诊断参考了“一年法则”,故在PD症状的持续时间方面有较大差异,但从表1中也能看到有多例患者并不符合“一年法则”,如第3、8和15号患者。
序号 临床诊断 性别 年龄(岁) MMSE评分(分) 帕金森病症状持续时间(年) 痴呆确诊时间(年) 1 PDD 男 69 27 8.6 2.3 2 PDD 男 72 19 10.8 3.5 3 PDD 男 67 24 4.3 3.8 4 PDD 男 74 21 13.2 3.9 5 PDD 男 57 22 5.6 1.1 6 PDD 男 73 23 12.3 4.5 7 PDD 女 76 20 18.9 5.9 8 PDD 女 62 25 3.8 2.8 9 PDD 女 79 17 15.9 5.8 10 PDD 女 70 18 7.1 2.9 11 DLB 男 63 18 2.4 2.6 12 DLB 男 62 16 1.5 0.7 13 DLB 男 80 11 3.6 3.3 14 DLB 男 69 15 3.1 3.0 15 DLB 男 73 26 2.6 1.1 16 DLB 男 78 20 5.1 7.6 17 DLB 女 71 29 3.9 5.0 18 DLB 女 76 24 4.3 6.2 19 DLB 女 68 24 3.2 5.0 20 DLB 女 70 19 4.7 5.8 21 DLB 女 72 17 4.5 7.0 注:表中,MMSE:简易智能状态检查量表;PDD:帕金森病痴呆;DLB:路易体痴呆。 表 1 21例患者的临床诊断和基本信息
Table 1. Clinical diagnosis and basic information of 21 patients
组别 例数 年龄(岁) MMSE评分(分) 帕金森病症状持续时间(年) 痴呆确诊时间(年) PDD组 10 69.90±6.57 21.60±3.20 10.05±5.06 3.65±1.50 DLB组 11 71.09±5.65 19.91±5.34 3.54±1.10 4.30±2.32 t值 −0.447 0.868 4.169 −0.754 P值 0.660 0.396 0.001 0.460 注:表中,MMSE:简易智能状态检查量表;PDD:帕金森病痴呆;DLB:路易体痴呆。 表 2 2组患者临床资料的比较(
)$\scriptstyle{{\bar x }}\pm{{s}}}$ Table 2. Comparison of clinical data between the two groups(
)$\scriptstyle{{\bar x }}\pm{{s}}}$ -
表3分别给出了PDD和DLB组的6处不同脑区(额叶、顶叶、颞叶、枕叶、丘脑、纹状体)相对于小脑的11C-PIB SUVmean比值。DLB组各脑区的11C-PIB SUVmean比值均高于PDD组,2组之间额叶和纹状体的差异均有统计学意义。图1所示2例患者的PET/CT脑显像11C-PIB脑分布图,图中可见2例患者的额叶区对显像剂的摄取存在明显差异。
组别 例数 额叶 顶叶 颞叶 枕叶 丘脑 纹状体 PDD组 10 1.21±0.25 1.17±0.29 1.12±0.22 1.16±0.17 1.06±0.21 1.20±0.21 DLB组 11 1.52±0.28 1.40±0.33 1.31±0.25 1.32±0.25 1.20±0.14 1.46±0.26 t值 −2.596 −1.628 −1.878 −1.657 −1.839 −2.504 P值 0.018 0.120 0.076 0.114 0.082 0.022 注:表中,PIB:匹兹堡化合物 B;SUVmean:平均标准化摄取值;PDD:帕金森病痴呆;DLB:路易体痴呆。 表 3 2组患者不同脑区相对于小脑的11C-PIB SUVmean比值(
)$\scriptstyle{{\bar x }}\pm{{s}}$ Table 3. 11C-PIB SUVmean ratios in different brain regions relative to cerebellum in the two groups(
)$\scriptstyle{{\bar x }}\pm{{s}}$ -
由表4可见,DLB组的tau蛋白平均浓度高于PDD组,而Aβ42和丛生蛋白的平均浓度均低于PDD组,且2组之间tau蛋白和丛生蛋白的浓度差异均有统计学意义。
组别 例数 tau蛋白(ng/L) Aβ42(ng/L) 丛生蛋白(μg/L) PDD组 10 344.1±133.37 644.70±311.77 8358.30±3014.51 DLB组 11 582.7±304.50 491.73±136.54 5219.45±1999.10 t值 −2.283 1.481 2.838 P值 0.034 0.155 0.011 注:表中,Aβ:β淀粉样蛋白;PDD:帕金森病痴呆;DLB:路易体痴呆。 表 4 2组患者脑脊液中不同蛋白的检测结果(
)$\scriptstyle{{\bar x }}\pm{{s}}$ Table 4. Test results of different proteins in cerebrospinal fluid of patients in the two groups(
)$\scriptstyle{{\bar x }}\pm{{s}}$
帕金森病痴呆和路易体痴呆在11C-PIB PET/CT脑显像及脑脊液检测中的差异分析
Analysis of the differences between Parkinsons disease dementia and dementia with Lewy bodies in 11C-PIB PET/CT brain imaging and cerebrospinal fluid test
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摘要:
目的 通过11C-匹兹堡化合物B(PIB)PET/CT显像及脑脊液中不同蛋白的检测,分析帕金森病痴呆(PDD)和路易体痴呆(DLB)患者在影像学和生物标志物方面的差异。 方法 选取2011年6月至2018年2月已被临床诊断为PDD患者10例(PDD组),其中男性6例、女性4例,年龄57~79(69.90±6.57)岁;DLB患者11例(DLB组),其中男性6例、女性5例,年龄62~80(71.09±5.65)岁。使用11C-PIB PET/CT进行脑扫描,分别测定额叶、顶叶、颞叶、枕叶、丘脑、纹状体与小脑的平均标准化摄取值(SUVmean)的比值。采用双抗夹心酶联免疫吸附法测定脑脊液中tau蛋白、β淀粉样蛋白42(Aβ42)和丛生蛋白的浓度。2组患者不同脑区相对于小脑的SUVmean比值、脑脊液不同蛋白水平的比较,均采用t检验。 结果 DLB患者各脑区相对于小脑的11C-PIB SUVmean的比值均高于PDD患者,且2组在额叶(DLB组:1.52±0.28,PDD组:1.21±0.25)、纹状体(DLB组:1.46±0.26,PDD组:1.20±0.21)之间的差异有统计学意义(t=−2.596、−2.504,P=0.018、0.022)。DLB组的tau蛋白水平[(582.7±304.50) ng/L]高于PDD组[(344.10±133.37 ) ng/L],而Aβ42、丛生蛋白的水平[(491.73±136.54) ng/L、(5219.45±1999.10) μg/L]均低于PDD组[(644.70±311.77) ng/L、(8358.30±3014.51) μg/L],且2组之间tau蛋白和丛生蛋白的水平差异均有统计学意义(t=−2.283、2.838,P=0.034、0.011)。 结论 PDD和DLB在11C-PIB PET/CT脑显像及脑脊液检测中存在多项明显差异,可为临床的鉴别诊断提供依据。 -
关键词:
- 正电子发射断层显像计算机体层摄影术 /
- 帕金森病痴呆 /
- 路易体痴呆 /
- 脑脊液 /
- 匹兹堡化合物B
Abstract:Objective To analyze differences in the imaging and biomarkers of patients with Parkinson disease dementia(PDD) and those with dementia with Lewy bodies(DLB) by 11C-pittsburgh compound B(PIB) PET/CT imaging and testing of different proteins in the cerebrospinal fluid. Methods A total of 10 PDD patients(PDD group) including six males and four females, aged 57–79 years(mean, 69.9±6.57 years) and 11 DLB patients(DLB group) including six males and five females, aged 62–80 years(mean, 71.09±5.65 years), clinically diagnosed from June 2011 to February 2018 were recruited to this study. Brain scans were performed using 11C-PIB PET/CT to measure the mean standardized uptake value(SUVmean) ratios of the frontal lobe, parietal lobe, temporal lobe, occipital lobe, thalamus, and striatum to cerebellum. The concentrations of tau, amyloid β-protein42(Aβ42), and cluster proteins in the cerebrospinal fluid were determined by double-antibody sandwich enzyme-linked immunosorbent assay. T test was used to compare the SUVmean ratio of different brain regions to that of the cerebellum, as well as the protein levels of cerebrospinal fluid between the two groups. Results The ratio of 11C-PIB SUVmean in each brain region relative to that in the cerebellum was higher in DLB patients than in PDD patients, and differences between the two groups in the frontal lobe(DLB group: 1.52±0.28, PDD group: 1.21±0.25) and striatum(DLB group: 1.46±0.26, PDD group: 1.20±0.21) were statistically significant(t=–2.596, –2.504, P=0.018, 0.022). Tau levels in the DLB group[(582.7±304.50) ng/L] were higher than those in the PDD group[(344.10±133.37) ng/L]; by contrast, levels of Aβ42 and cluster proteins[(491.73±136.54) ng/L, (5219.45±1999.10) μg/L] in the DLB group were lower than those in the PDD group[(644.70±311.77) ng/L, (8358.30±3014.51) μg/L]. Tau and cluster proteins showed statistically significant differences between the two groups(t=–2.283, 2.838, P=0.034, 0.011). Conclusion PDD and DLB show many obvious differences during 11C-PIB PET/CT brain imaging and cerebrospinal fluid testing, and these differences can provide a basis for clinical differential diagnosis. -
表 1 21例患者的临床诊断和基本信息
Table 1. Clinical diagnosis and basic information of 21 patients
序号 临床诊断 性别 年龄(岁) MMSE评分(分) 帕金森病症状持续时间(年) 痴呆确诊时间(年) 1 PDD 男 69 27 8.6 2.3 2 PDD 男 72 19 10.8 3.5 3 PDD 男 67 24 4.3 3.8 4 PDD 男 74 21 13.2 3.9 5 PDD 男 57 22 5.6 1.1 6 PDD 男 73 23 12.3 4.5 7 PDD 女 76 20 18.9 5.9 8 PDD 女 62 25 3.8 2.8 9 PDD 女 79 17 15.9 5.8 10 PDD 女 70 18 7.1 2.9 11 DLB 男 63 18 2.4 2.6 12 DLB 男 62 16 1.5 0.7 13 DLB 男 80 11 3.6 3.3 14 DLB 男 69 15 3.1 3.0 15 DLB 男 73 26 2.6 1.1 16 DLB 男 78 20 5.1 7.6 17 DLB 女 71 29 3.9 5.0 18 DLB 女 76 24 4.3 6.2 19 DLB 女 68 24 3.2 5.0 20 DLB 女 70 19 4.7 5.8 21 DLB 女 72 17 4.5 7.0 注:表中,MMSE:简易智能状态检查量表;PDD:帕金森病痴呆;DLB:路易体痴呆。 表 2 2组患者临床资料的比较(
)$\scriptstyle{{\bar x }}\pm{{s}}}$ Table 2. Comparison of clinical data between the two groups(
)$\scriptstyle{{\bar x }}\pm{{s}}}$ 组别 例数 年龄(岁) MMSE评分(分) 帕金森病症状持续时间(年) 痴呆确诊时间(年) PDD组 10 69.90±6.57 21.60±3.20 10.05±5.06 3.65±1.50 DLB组 11 71.09±5.65 19.91±5.34 3.54±1.10 4.30±2.32 t值 −0.447 0.868 4.169 −0.754 P值 0.660 0.396 0.001 0.460 注:表中,MMSE:简易智能状态检查量表;PDD:帕金森病痴呆;DLB:路易体痴呆。 表 3 2组患者不同脑区相对于小脑的11C-PIB SUVmean比值(
)$\scriptstyle{{\bar x }}\pm{{s}}$ Table 3. 11C-PIB SUVmean ratios in different brain regions relative to cerebellum in the two groups(
)$\scriptstyle{{\bar x }}\pm{{s}}$ 组别 例数 额叶 顶叶 颞叶 枕叶 丘脑 纹状体 PDD组 10 1.21±0.25 1.17±0.29 1.12±0.22 1.16±0.17 1.06±0.21 1.20±0.21 DLB组 11 1.52±0.28 1.40±0.33 1.31±0.25 1.32±0.25 1.20±0.14 1.46±0.26 t值 −2.596 −1.628 −1.878 −1.657 −1.839 −2.504 P值 0.018 0.120 0.076 0.114 0.082 0.022 注:表中,PIB:匹兹堡化合物 B;SUVmean:平均标准化摄取值;PDD:帕金森病痴呆;DLB:路易体痴呆。 表 4 2组患者脑脊液中不同蛋白的检测结果(
)$\scriptstyle{{\bar x }}\pm{{s}}$ Table 4. Test results of different proteins in cerebrospinal fluid of patients in the two groups(
)$\scriptstyle{{\bar x }}\pm{{s}}$ 组别 例数 tau蛋白(ng/L) Aβ42(ng/L) 丛生蛋白(μg/L) PDD组 10 344.1±133.37 644.70±311.77 8358.30±3014.51 DLB组 11 582.7±304.50 491.73±136.54 5219.45±1999.10 t值 −2.283 1.481 2.838 P值 0.034 0.155 0.011 注:表中,Aβ:β淀粉样蛋白;PDD:帕金森病痴呆;DLB:路易体痴呆。 -
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