Hong Jeong Hoon, Kim Yue Kyung, Park Jae Seol, Lee Ji Eun, Oh Mi Sun, Chung Eun Joo, Kim Jeong-Yeon, Sung Young-Hee, Lyoo Chul Hyoung, Lee Jae Hyeok, Kwon Do-Young, Kim Hyun Sook, Shin Hae-Won, Park Sun Ah, Park In-Seok, Kim Joong-Seok, Lee Phil Hyu, Koh Seong-Beom, Baik Jong Sam, Kim Sang Jin, Ma Hyeo-Il, Kim Jae Woo, Kim Yun Joong
ILSONG Institute of Life Science, Hallym University, Anyang, South Korea.
Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea.
J Clin Neurosci. 2017 Feb;36:108-113. doi: 10.1016/j.jocn.2016.10.013. Epub 2016 Nov 10.
Aside from the glucocerebrosidase gene, the genetic risk factors for cognitive decline in Parkinson's disease (PD) are controversial. We investigated whether the G2385R polymorphism in leucine-rich repeat kinase 2 gene (LRRK2), a risk variant for the development of PD in East Asians, is associated with cognitive dysfunction in PD. We recruited 299 PD patients, consisting of 23 carriers and 276 non-carriers of LRRK2 G2385R, from 14 centers. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA). PD with cognitive dysfunction was defined as an MMSE Z score that, adjusting for age at study entry and years of education, was below -1.0 standard deviations. In multivariate analysis, PD duration, age at study entry and depression were significant risk factors for cognitive dysfunction as assessed by MMSE performance or the MoCA. In linear regression analysis of the association between MMSE Z scores and PD duration, there was no significant difference associated with the LRRK2 G2385R genotype. The interaction terms between PD duration and the LRRK2 G2385R genotype were not significant for the MMSE Z score but were significant for the MoCA. In conclusion, the LRRK2 G2385R genotype may not be associated with cognitive dysfunction in PD.
除了葡萄糖脑苷脂酶基因外，帕金森病（PD）认知功能衰退的遗传风险因素仍存在争议。我们研究了富含亮氨酸重复激酶2基因（LRRK2）中的G2385R多态性（东亚人群中PD发病的一个风险变异）是否与PD患者的认知功能障碍有关。我们从14个中心招募了299名PD患者，其中包括23名LRRK2 G2385R携带者和276名非携带者。使用简易精神状态检查表（MMSE）或蒙特利尔认知评估量表（MoCA）评估整体认知功能。伴有认知功能障碍的PD被定义为在根据研究入组时的年龄和受教育年限进行调整后，MMSE Z评分低于-1.0标准差。在多变量分析中，PD病程、研究入组时的年龄和抑郁是通过MMSE表现或MoCA评估的认知功能障碍的显著风险因素。在MMSE Z评分与PD病程之间关联的线性回归分析中，LRRK2 G2385R基因型无显著差异。PD病程与LRRK2 G2385R基因型之间的交互项对MMSE Z评分无显著意义，但对MoCA有显著意义。总之，LRRK2 G2385R基因型可能与PD患者的认知功能障碍无关。
