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目的探索帕金森病(Parkinson disease,PD)患者震颤型与姿势步态异常型等不同运动表型与认知功能之间的关系及其机制。方法选择110例PD患者,采用统一帕金森病评分量表评价运动症状,并分为震颤型(tremor-dominant,TD)70例,姿势步态异常型(postural instability and gait difficulty,PIGD)40例;采用一系列非运动症状量表评价非运动症状;检测110例PD患者脑脊液中β淀粉样蛋白(βamyloid,Aβ)1-42、总tau、磷酸化tau蛋白,磷酸化位点分别是:231苏安酸位点(P-tau231t)、181苏安酸位点(P-tau181t)、396丝氨酸位点(P-tau396s)和199丝氨酸位点(P-tau199s)水平的变化;将(total tau,T-tau)震颤评分和姿势步态异常评分与脑脊液中上述病理蛋白水平进行相关性分析。结果 (1)PIGD组患者姿势步态异常、强直和运动迟缓评分较TD组明显升高,而震颤评分明显下降,MoC A中注意力评分明显低于TD组,生活质量较TD组患者下降更明显。(2)PIGD组和TD组脑脊液中总tau、P-tau231t、P-tau181t、P-tau396s和P-tau199s水平较对照组显著升高(P<0.05);脑脊液中Aβ1-42水平较对照组明显降低;PIGD组P-tau181t水平较TD组和对照组显著升高,Aβ1-42水平较TD组和对照组显著降低(P<0.05)。(3)单因素分析发现,PD患者姿势步态异常评分与脑脊液P-tau181t水平、H-Y分期、病程、焦虑、抑郁、疲劳及淡漠呈显著正相关,与脑脊液Aβ1-42及认知功能呈显著负相关;多重线性回归分析发现,PIGD组患者姿势步态异常评分与脑脊液中P-tau181t水平、H-Y分期呈显著正相关,与Mo CA水平呈显著负相关(P<0.05)。结论 PIGD组患者,姿势步态异常、强直和运动迟缓均明显重于TD组,生活质量较TD组明显下降。PD患者姿势步态异常表型与脑脊液中P-tau181t水平呈正相关,与脑脊液中Aβ1-42水平呈负相关;PIGD组患者较TD患者更易发生认知障碍,Aβ1-42过量沉积与脑内脑脊液中P-tau181t水平升高,导致认知相关脑区神经元变性死亡,可能是PD患者姿势步态异常与认知障碍的潜在病理生理机制之一。
Objective To explore the relationship between the different motor phenotypes and cognitive function in patients with Parkinson’s disease (PD) and their abnormalities. Methods One hundred and ten PD patients were selected. The Parkinson’s disease score was used to evaluate motor symptoms. The patients were divided into 70 cases of tremor-dominant (TD), 40 cases of postural instability and gait difficulty (PIGD) ; A series of non-motor symptom scales were used to evaluate non-motor symptoms; the detection of β amyloid (Aβ) 1-42, total tau, phosphorylated tau and phosphorylation sites in cerebrospinal fluid of 110 PD patients were: 231 (P-tau231t), 181 threonine (P-tau181t), 396 serine (P-tau396s) and 199 serine loci (P-tau199s) , T-tau) tremor score and postural gait abnormality score and cerebrospinal fluid in the above pathological protein level correlation analysis. Results (1) The posture gait anomaly, rigidity and bradykinesia scores of PIGD group were significantly higher than those of TD group, while the tremor score was significantly decreased. The score of attention in MoC A was significantly lower than that of TD group. The quality of life was lower than that of TD group obvious. (2) The levels of total tau, P-tau231t, P-tau181t, P-tau396s and P-tau199s in cerebrospinal fluid in PIGD group and TD group were significantly higher than those in control group (P < P-tau181t in PIGD group was significantly higher than that in TD group and control group, while Aβ1-42 level in PIGD group was significantly lower than that in TD group and control group (P <0.05). (3) Univariate analysis showed that the abnormal gait scores of PD patients were positively correlated with the levels of P-tau181t, HY stage, disease course, anxiety, depression, fatigue and apathy in cerebrospinal fluid and were significantly correlated with cerebrospinal fluid Aβ1-42 and cognitive function Multiple linear regression analysis showed that abnormal gait scores of PIGD patients were positively correlated with P-tau181t level and HY stage in cerebrospinal fluid, and negatively correlated with MoCA level (P <0.05). Conclusion In patients with PIGD, posture gait abnormalities, rigidity and motor retardation were significantly higher than those in TD group, and the quality of life was significantly lower than that in TD group. PD patients with abnormal gait posture and cerebrospinal fluid P-tau181t levels were positively correlated with cerebrospinal fluid Aβ1-42 levels was negatively correlated; PIGD patients were more susceptible to cognitive impairment in patients with TD, Aβ1-42 over-deposition and cerebral cerebrospinal fluid P-tau181t levels, leading to degeneration and death of neurons in cognitive-related brain regions may be one of the potential pathophysiological mechanisms of PD gait abnormalities and cognitive disorders.