APOE, MAPT, and SNCA genes and cognitive performance in Parkinson disease.
APOE, MAPT, and SNCA genes and cognitive performance in Parkinson disease.
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DOI：
10.1001/jamaneurol.2014.1455
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发表时间：
2014-11
期刊：
影响因子：
29
通讯作者：
Zabetian, Cyrus P.
中科院分区：
文献类型：
--
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.
认知功能障碍（CI）是帕金森病（PD）中常见的致残性问题，目前尚不清楚，也难以治疗。识别影响PD早期认知功能障碍的认知下降率或模式的遗传变异可能会更清楚地了解这一重要的非运动功能的发病机制。确定APOE、MAPT和SNCA基因的常见变异是否与PD患者的认知能力相关。我们研究了来自美国6个学术中心的1，079名PD患者，这些患者接受了记忆（霍普金斯言语学习测试-修订版[HVLT-R]）、注意力/执行功能（字母-数字排序和连线测试）、语言处理（语义和音素言语流畅性）、视觉空间技能（线条方向的本顿判断）和整体认知功能（蒙特利尔认知评估[莫卡]）评估。对受试者进行APOE ε2/ε3/ε4、MAPT H1/H2单倍型和SNCA rs356219基因分型。采用线性回归法检验基因型与基线认知能力之间的相关性，并对年龄、性别、受教育年限、疾病持续时间和部位进行了调整。我们使用Bonferroni校正来调整对每个基因进行的九次比较。九个变量来自七个心理测试。APOE ε4与HVLT-R总体学习成绩较低相关（P=6.7×10−6;校正P [Pc]=6.0×10−5），延迟回忆（P=0.001; Pc=0.009），识别辨别指数（P=0.004; Pc=0.04）、语义语言流畅性（P=0.002; Pc=0.018）、字母-数字排序（P=1 × 10−5; Pc=9 × 10−5）和路径B-A（P=0.002; Pc=0.018）。在645名非痴呆患者的亚组中，APOE ε4与HVLT-R总学习（P=0.005; Pc=0.045）和语义语言流畅性（P=0.005; Pc=0.045）的较低评分相关。MAPT和SNCA变异与任何测试的分数都不相关。我们的数据表明，APOE ε4是PD多个领域认知功能的重要预测因子。在非痴呆PD患者中，APOE ε4仅与单词列表学习和语义语言流畅性的较低表现相关，这种模式比PD更典型地出现在早期阿尔茨海默病中的认知缺陷。
Cognitive impairment (CI) is a common and disabling problem in Parkinson’s disease (PD) that is not well understood and is difficult to treat. Identification of genetic variants that influence the rate of cognitive decline or pattern of early cognitive deficits in PD might provide a clearer understanding of the etiopathogenesis of this important non-motor feature. To determine if common variation in the APOE, MAPT, and SNCA genes is associated with cognitive performance in patients with PD. We studied 1,079 PD patients from six academic centers in the U.S. who underwent assessments of memory (Hopkins Verbal Learning Test-Revised [HVLT-R]), attention/executive function (Letter-Number Sequencing and Trail Making Test), language processing (semantic and phonemic verbal fluency), visuospatial skills (Benton Judgment of Line Orientation) and global cognitive function (Montreal Cognitive Assessment [MoCA]). Subjects were genotyped for APOE ε2/ε3/ε4, MAPT H1/H2 haplotypes, and SNCA rs356219. Linear regression was used to test for association between genotype and baseline cognitive performance adjusting for age, sex, years of education, disease duration, and site. We used a Bonferroni correction to adjust for the nine comparisons that were performed for each gene. Nine variables derived from seven psychometric tests. APOE ε4 was associated with lower performance on HVLT-R total learning (P=6.7×10−6; corrected P [Pc]=6.0×10−5), delayed recall (P=0.001; Pc=0.009), and recognition discrimination index (P=0.004; Pc=0.04), and semantic verbal fluency (P=0.002; Pc=0.018), Letter-Number sequencing (P=1 × 10−5; Pc=9 × 10−5), and Trails B-A (P=0.002; Pc=0.018). In a subset of 645 non-demented patients, APOE ε4 was associated with lower scores on HVLT-R total learning (P=0.005; Pc=0.045) and semantic verbal fluency (P=0.005; Pc=0.045). MAPT and SNCA variants were not associated with scores on any tests. Our data indicate that APOE ε4 is an important predictor of cognitive function in PD across multiple domains. Among non-demented PD patients, APOE ε4 was only associated with lower performance on word list learning and semantic verbal fluency, a pattern more typical of the cognitive deficits seen in early Alzheimer’s disease than PD.
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DOI：
10.3233/jpd-130189
发表时间：
2013
期刊：
Journal of Parkinson's disease
影响因子：
--
作者：
Cholerton BA;Zabetian CP;Quinn JF;Chung KA;Peterson A;Espay AJ;Revilla FJ;Devoto J;Watson GS;Hu SC;Edwards KL;Montine TJ;Leverenz JB
通讯作者：
Leverenz JB
DOI：
10.1002/mds.25062
发表时间：
2012-08
期刊：
Movement disorders : official journal of the Movement Disorder Society
影响因子：
--
作者：
Goldman JG;Weis H;Stebbins G;Bernard B;Goetz CG
通讯作者：
Goetz CG
影响因子：
2.6
作者：
Kurz, Martin Wilhelm;Dekomien, Gabriele;Alves, Guido
通讯作者：
Alves, Guido
影响因子：
9.9
作者：
Aarsland, D.;Bronnick, K.;Alves, G.
通讯作者：
Alves, G.
DOI：
10.1111/j.1532-5415.2000.tb06891.x
发表时间：
2000-08-01
影响因子：
6.3
作者：
Aarsland, D;Larsen, JP;Laake, K
通讯作者：
Laake, K