Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA.
Mov Disord. 2012 Apr;27(4):512-8. doi: 10.1002/mds.24946. Epub 2012 Feb 16.
The role of genetic factors in cognitive decline associated with Parkinson's disease (PD) is unclear. We examined whether variations in apolipoprotein E (APOE), microtubule-associated protein tau (MAPT), or catechol-O-methytransferase (COMT) genotypes are associated with cognitive decline in PD. We performed a prospective cohort study of 212 patients with a clinical diagnosis of PD. 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 APOE was associated with more rapid decline (loss of 2.9; 95% confidence interval [CI]: 1.7-4.1) of more points per year; P < 0.001) in total score and an increased risk of a ≥ 10 point drop during the follow-up period (hazard ratio, 2.8; 95% CI: 1.4-5.4; P = 0.003). MAPT haplotype and COMT genotype were associated with measures of memory and attention, respectively, over the entire follow-up period, but not with the overall rate of cognitive decline. These results confirm and extend previously described genetic associations with cognitive decline in PD and imply that individual genes may exert effects on specific cognitive domains or at different disease stages. Carrying at least one APOE ε4 allele is associated with more rapid cognitive decline in PD, supporting the idea of a component of shared etiology between PD dementia and Alzheimer's disease. Clinically, these results suggest that genotyping can provide information about the risk of future cognitive decline for PD patients.
遗传因素在帕金森病（PD）相关认知下降中的作用尚不清楚。我们研究了载脂蛋白 E（APOE）、微管相关蛋白 tau（MAPT）或儿茶酚-O-甲基转移酶（COMT）基因变异是否与 PD 患者的认知下降有关。我们对 212 例临床诊断为 PD 的患者进行了前瞻性队列研究。主要结局是 Mattis 痴呆评定量表第 2 版评分的变化。线性混合效应模型和生存分析用于测试基因型与认知功能随时间变化的相关性。APOE 的 ε4 等位基因与每年更多的认知功能下降（每年损失 2.9 分；95%置信区间[CI]：1.7-4.1；P<0.001）有关，且随访期间认知功能下降≥10 分的风险增加（危险比，2.8；95%CI：1.4-5.4；P=0.003）。在整个随访期间，MAPT 单倍型与 COMT 基因型分别与记忆和注意力的测量值相关，但与认知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 PD 认知下降相关的遗传关联，并表明个别基因可能对特定认知域或在不同疾病阶段发挥作用。至少携带一个 APOE ε4 等位基因与 PD 认知下降更快有关，支持 PD 痴呆与阿尔茨海默病之间存在共同病因的观点。从临床角度来看，这些结果表明基因分型可以为 PD 患者未来认知下降的风险提供信息。
