From the Department of Neurology (L.P.O., E.Y.L.N., S.-H.S., K.-Y.T., W.-L.A., E.-K.T., L.C.S.T.), Parkinson's Disease and Movement Disorders Centre, USA National Parkinson Foundation Centre of Excellence, National Neuroscience Institute; and Duke-NUS Graduate Medical School (J.C.A., W.-L.A., E.-K.T., L.C.S.T.), Singapore.
Neurology. 2015 Sep 22;85(12):1039-42. doi: 10.1212/WNL.0000000000001953. Epub 2015 Aug 26.
In a longitudinal follow-up study, we compared the clinical features and motor progression of patients with Parkinson disease (PD) who are carriers of the leucine-rich repeat kinase 2 (LRRK2) gene risk variants with patients who are noncarriers.
We prospectively evaluated a cohort of patients with PD for their clinical characteristics, disease severity, and LRRK2 genotype. Carriers of risk variants (G2385R, R1628P, S1647T) and noncarriers were classified separately. A longitudinal, linear mixed model analysis of motor score progression was performed to compare motor progression between the 2 groups. Motor score progression was defined as the difference between Unified Parkinson's Disease Rating Scale motor score at baseline and follow-up scores.
A total of 184 patients (122 risk variant carriers and 62 noncarriers) were evaluated and followed up for up to 6.5 years. No differences in demographics and baseline disease characteristics were found. In the longitudinal, linear mixed model analysis, risk variant carriers experienced greater rate of motor progression than noncarriers after 4 years from the date of diagnosis (p ≤ 0.018).
PD LRRK2 risk variant carriers showed greater motor progression after 4 years of disease duration compared with noncarrier patients, suggesting that these risk variants may facilitate neurodegeneration with increasing disease duration.
在一项纵向随访研究中，我们比较了携带富亮氨酸重复激酶 2（LRRK2）基因风险变异的帕金森病（PD）患者与非携带者的临床特征和运动进展。
我们前瞻性地评估了一组 PD 患者的临床特征、疾病严重程度和 LRRK2 基因型。将携带风险变异（G2385R、R1628P、S1647T）的患者和非携带者分别进行分类。对运动评分进展进行纵向线性混合模型分析，以比较两组之间的运动进展。运动评分进展定义为基线时统一帕金森病评定量表运动评分与随访评分之间的差异。
共评估和随访了 184 例患者（122 例风险变异携带者和 62 例非携带者），最长随访时间为 6.5 年。两组在人口统计学和基线疾病特征方面无差异。在纵向线性混合模型分析中，风险变异携带者在诊断后 4 年内的运动进展速度大于非携带者（p≤0.018）。
与非携带者患者相比，携带 PD LRRK2 风险变异的患者在疾病持续 4 年后表现出更大的运动进展，这表明这些风险变异可能随着疾病持续时间的延长而促进神经退行性变。
