Genetic influences on cognitive decline in Parkinson's disease.
Genetic influences on cognitive decline in Parkinson's disease.
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DOI：
10.1002/mds.24946
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发表时间：
2012-04
影响因子：
8.6
通讯作者：
Siderowf, Andrew
中科院分区：
文献类型：
--
作者：
Morley, James F.;Xie, Sharon X.;Hurtig, Howard I.;Stern, Matthew B.;Colcher, Amy;Horn, Stacy;Dahodwala, Nabila;Duda, John E.;Weintraub, Daniel;Chen-Plotkin, Alice S.;Van Deerlin, Vivianna;Falcone, Dana;Siderowf, Andrew
关键词：
遗传因素在帕金森病相关认知能力下降中的作用尚不清楚。我们研究了载脂蛋白 E、微管相关蛋白 tau 或儿茶酚-O-甲基转移酶基因型的变异是否与帕金森病的认知能力下降有关。我们对 212 名临床诊断为帕金森病的患者进行了一项前瞻性队列研究。主要结果是马蒂斯痴呆评定量表第 2 版评分的变化。使用线性混合效应模型和生存分析来测试基因型与认知功能随时间变化之间的关联。载脂蛋白 E 的 ε4 等位基因与总分更快下降（每年损失 2.9 分（95% CI，1.7-4.1）分，p<0.001）以及随访期间下降 ≥10 分的风险增加相关（HR 2.8，95% CI 1.4-5.4，p=0.003）。微管相关蛋白 tau 单倍型和儿茶酚-O-甲基转移酶基因型分别与整个随访期间的记忆力和注意力测量相关，但与认知能力下降的总体速度无关。这些结果证实并扩展了先前描述的与帕金森病认知衰退的遗传关联，并暗示个体基因可能对特定认知领域或不同疾病阶段产生影响。携带至少一个载脂蛋白 E ε4 等位基因与帕金森病的认知能力更快下降有关，这支持了帕金森病痴呆和阿尔茨海默病之间具有共同病因的观点。临床上，这些结果表明基因分型可以提供有关帕金森病患者未来认知能力下降风险的信息。
The role of genetic factors in cognitive decline associated with Parkinson's disease is unclear. We examined whether variations in apolipoprotein E, microtubule-associated protein tau or catechol-O-methytransferase genotypes are associated with cognitive decline in Parkinson's disease. We performed a prospective cohort study of 212 patients with a clinical diagnosis of Parkinson's disease. The primary outcome was change in Mattis Dementia Rating Scale version 2 score. Linear mixed-effects models and survival analysis were used to test for associations between genotypes and change in cognitive function over time. The ε4 allele of apoliporotein E was associated with more rapid decline (loss of 2.9 (95% CI, 1.7–4.1) more points/year, p<0.001) in total score and an increased risk of a ≥10 pointdrop during the follow-up period (HR 2.8, 95% CI 1.4–5.4, p=0.003). Microtubule-associated protein tau haplotype and catechol-O-methytransferase genotype were associated with measures of memory and attention, respectively, over the entire followup period but not with the overall rate of cognitive decline. These results confirm and extend previously described genetic associations with cognitive decline in Parkinson's disease and imply that individual genes may exert effects on specific cognitive domains or at different disease stages. Carrying at least one apolipoprotein E ε4 allele is associated with more rapid cognitive decline in Parkinson's disease, supporting the idea of a component of shared etiology between Parkinson's disease dementia and Alzheimer disease. Clinically, these results suggest genotyping can provide information about the risk of future cognitive decline for Parkinson's disease patients.
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影响因子：
11.2
作者：
Goris, An;Williams-Gray, Caroline H.;Sawcer, Stephen J.
通讯作者：
Sawcer, Stephen J.
影响因子：
11.2
作者：
Chen-Plotkin, Alice S.;Hu, William T.;Siderowf, Andrew;Weintraub, Daniel;Gross, Rachel Goldmann;Hurtig, Howard I.;Xie, Sharon X.;Arnold, Steven E.;Grossman, Murray;Clark, Christopher M.;Shaw, Leslie M.;McCluskey, Leo;Elman, Lauren;Van Deerlin, Vivianna M.;Lee, Virginia M. -Y.;Soares, Holly;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
8.6
作者：
Compta, Yaroslau;Marti, Maria J.;Tolosa, Eduardo
通讯作者：
Tolosa, Eduardo
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：
Aarsland, D;Andersen, K;Kragh-Sorensen, P
通讯作者：
Kragh-Sorensen, P