Features of GBA-associated Parkinson's disease at presentation in the UK Tracking Parkinson's study.
Features of GBA-associated Parkinson's disease at presentation in the UK Tracking Parkinson's study.
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DOI：
10.1136/jnnp-2017-317348
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
PRoBaND clinical consortium
中科院分区：
文献类型：
--
作者：
Malek N;Weil RS;Bresner C;Lawton MA;Grosset KA;Tan M;Bajaj N;Barker RA;Burn DJ;Foltynie T;Hardy J;Wood NW;Ben-Shlomo Y;Williams NW;Grosset DG;Morris HR;PRoBaND clinical consortium
在一个大的英国患者队列中，研究葡萄糖脑苷脂酶（GBA）突变携带状态对帕金森病（PD）发病年龄、运动表型和基线评估时认知功能的影响。我们还分析了可能混淆认知功能评估的情绪和行为问题的普遍性。我们前瞻性招募帕金森病患者参与跟踪帕金森病研究。我们对所有最近确诊的患者（≤3.5岁）的GBA基因进行了完全测序。我们在诊断后平均1.3年的基线评估中检查了认知（蒙特利尔认知评估）和运动（运动障碍协会统一帕金森病评定量表第3部分）功能。我们使用逻辑回归来确定PD伴轻度认知功能障碍和PD伴痴呆的预测因子。我们研究了1893例PD患者：48例（2.5%）是已知戈谢病（GD）致病突变的杂合携带者; 117例（6.2%）具有非同义变异，以前与PD相关，28例（1.5%）患者携带GBA基因中未知意义的变异。L444 P是最常见的致病性GBA突变。与非携带者相比，携带致病性GBA突变的患者在发病时平均年轻5岁（P=0.02）。携带GD突变的PD患者没有增加PD的家族风险。与非携带者相比，携带GBA突变的患者更可能出现姿势不稳定步态困难表型（P=0.02）。与非携带者相比，携带GBA致病性突变的患者在调整年龄和疾病持续时间后具有更先进的Hoehn和Yahr分期（P=0.005）。GBA突变携带者和非携带者在疾病早期的认知功能没有差异。我们的研究证实了GBA突变对PD患者的发病年龄、疾病严重程度和运动表型的影响。在基线时，GBA突变携带者和非携带者之间的认知没有差异，这意味着在其他研究中报告的晚期疾病阶段的认知障碍/痴呆在最近诊断的病例中不存在。这为潜在的疾病修饰疗法提供了一个重要的机会窗口，可以防止GBA-PD中痴呆的发展。NCT 02881099;结果。
To examine the influence of the glucocerebrosidase (GBA) mutation carrier state on age at onset of Parkinson’s disease (PD), the motor phenotype and cognitive function at baseline assessment in a large cohort of UK patients. We also analysed the prevalence of mood and behavioural problems that may confound the assessment of cognitive function. We prospectively recruited patients with PD in the Tracking Parkinson’s study. We fully sequenced the GBA gene in all recently diagnosed patients (≤3.5 years). We examined cognitive (Montreal Cognitive Assessment) and motor (Movement Disorder Society Unified Parkinson’s Disease Rating Scale part 3) function at a baseline assessment, at an average of 1.3 years after diagnosis. We used logistic regression to determine predictors of PD with mild cognitive impairment and PD with dementia. We studied 1893 patients with PD: 48 (2.5%) were heterozygous carriers for known Gaucher’s disease (GD) causing pathogenic mutations; 117 (6.2%) had non-synonymous variants, previously associated with PD, and 28 (1.5%) patients carried variants of unknown significance in the GBA gene. L444P was the most common pathogenic GBA mutation. Patients with pathogenic GBA mutations were on average 5 years younger at disease onset compared with non-carriers (P=0.02). PD patients with GD-causing mutations did not have an increased family risk of PD. Patients with GBA mutations were more likely to present with the postural instability gait difficulty phenotype compared with non-carriers (P=0.02). Patients carrying pathogenic mutations in GBA had more advanced Hoehn and Yahr stage after adjustment for age and disease duration compared with non-carriers (P=0.005). There were no differences in cognitive function between GBA mutation carriers and non-carriers at this early disease stage. Our study confirms the influence of GBA mutations on the age of onset, disease severity and motor phenotype in patients with PD. Cognition did not differ between GBA mutation carriers and non-carriers at baseline, implying that cognitive impairment/dementia, reported in other studies at a later disease stage, is not present in recently diagnosed cases. This offers an important window of opportunity for potential disease-modifying therapy that may protect against the development of dementia in GBA-PD. NCT02881099; Results.
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DOI：
10.1002/mds.26359
发表时间：
2016-01
期刊：
Movement disorders : official journal of the Movement Disorder Society
影响因子：
--
作者：
Mata IF;Leverenz JB;Weintraub D;Trojanowski JQ;Chen-Plotkin A;Van Deerlin VM;Ritz B;Rausch R;Factor SA;Wood-Siverio C;Quinn JF;Chung KA;Peterson-Hiller AL;Goldman JG;Stebbins GT;Bernard B;Espay AJ;Revilla FJ;Devoto J;Rosenthal LS;Dawson TM;Albert MS;Tsuang D;Huston H;Yearout D;Hu SC;Cholerton BA;Montine TJ;Edwards KL;Zabetian CP
通讯作者：
Zabetian CP
影响因子：
29
作者：
Mata, Ignacio F.;Leverenz, James B.;Weintraub, Daniel;Trojanowski, John Q.;Hurtig, Howard I.;Van Deerlin, Vivianna M.;Ritz, Beate;Rausch, Rebecca;Rhodes, Shannon L.;Factor, Stewart A.;Wood-Siverio, Cathy;Quinn, Joseph F.;Chung, Kathryn A.;Peterson, Amie L.;Espay, Alberto J.;Revilla, Fredy J.;Devoto, Johnna;Hu, Shu-Ching;Cholerton, Brenna A.;Wan, Jia Y.;Montine, Thomas J.;Edwards, Karen L.;Zabetian, Cyrus P.
通讯作者：
Zabetian, Cyrus P.
影响因子：
11
作者：
HUGHES, AJ;DANIEL, SE;LEES, AJ
通讯作者：
LEES, AJ
影响因子：
9.9
作者：
Alcalay, R. N.;Caccappolo, E.;Marder, K.
通讯作者：
Marder, K.
影响因子：
9.9
作者：
Dalrymple-Alford, J. C.;MacAskill, M. R.;Anderson, T. J.
通讯作者：
Anderson, T. J.