title: Lack of association between LRRK2 G2385R and cognitive dysfunction in Korean patients with Parkinson's disease.
abstract: 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.
authors.affiliation: ILSONG Institute of Life Science, Hallym University, Anyang, South Korea.
authors.forename: Jeong Hoon
authors.initials: JH
authors.lastname: Hong
authors.affiliation: Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea.
authors.forename: Yue Kyung
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea.
authors.forename: Jae Seol
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Neurology, National Health Insurance Service Ilsan Hospital, Ilsan, South Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea.
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Oh
authors.affiliation: Department of Neurology, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Chung
authors.affiliation: Department of Neurology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, South Korea.
authors.forename: Jeong-Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Neurology, Gachon University College of Medicine, Incheon, South Korea.
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Sung
authors.affiliation: Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Chul Hyoung
authors.initials: CH
authors.lastname: Lyoo
authors.affiliation: Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, South Korea.
authors.forename: Jae Hyeok
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Neurology, Korea University College of Medicine, Ansan Hospital, Ansan, South Korea.
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Kwon
authors.affiliation: Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Neurology, Chung-Ang University College of Medicine, Seoul, South Korea.
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Shin
authors.affiliation: Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea.
authors.forename: Sun Ah
authors.initials: SA
authors.lastname: Park
authors.affiliation: Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: In-Seok
authors.initials: IS
authors.lastname: Park
authors.affiliation: Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Joong-Seok
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Phil Hyu
authors.initials: PH
authors.lastname: Lee
authors.affiliation: Department of Neurology, Korea University College of Medicine at Guro Hospital, Seoul, South Korea.
authors.forename: Seong-Beom
authors.initials: SB
authors.lastname: Koh
authors.affiliation: Department of Neurology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, South Korea.
authors.forename: Jong Sam
authors.initials: JS
authors.lastname: Baik
authors.affiliation: Department of Neurology, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea.
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea.
authors.forename: Hyeo-Il
authors.initials: HI
authors.lastname: Ma
authors.affiliation: Department of Neurology, Dong-A University School of Medicine, Busan, South Korea.
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Kim
authors.affiliation: 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; Hallym Institute of Translational Genomics and Bioinformatics, Hallym University Medical Center, Anyang, South Korea. Electronic address: yunkim@hallym.ac.kr.
authors.forename: Yun Joong
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: Cognitive impairment; Genetic risk factor; Idiopathic Parkinson’s disease; Leucine-rich repeat kinase 2; Polymorphism