Li Liu1, Jia Li1, Wei Quan1, Yidan Qin1, Qinghui Zhang1, Xiaochen Pei1, Hang Su1, Jing Xu1, Jiajun Chen2. 1. Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, 130000, Jilin, China. 2. Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, 130000, Jilin, China. cjj@jlu.edu.cn.
Abstract
OBJECTIVES: Glucocerebrosidase (GBA) gene may be a risk factor for dementia with Lewy bodies (DLB). However, due to the small number of existing studies and the small sample size of previous investigations, it is necessary to conduct objective and quantitative analyses of the association between GBA variants and DLB. There is no consensus regarding the relationship between GBA and the clinical characteristics of DLB. Therefore, we conducted multiple systematic reviews and meta-analyses with a particular focus on the age of onset, sex, and cognitive impairment. METHODS: PubMed, Cochrane, and EMBASE databases were searched to retrieve related studies. The odds ratios and 95% confidence interval were calculated to determine the association between GBA and DLB and between GBA and the clinical characteristics of DLB. RESULTS: Our meta-analysis confirmed that the GBA variant rate was significantly higher in the DLB group than in the control group, as were the variant rates of L444P, N370S, and E326K, whereas the variant rate of T369M showed no significant difference between the groups. Furthermore, the relevant literature was summarised again for meta-analyses. The GBA variant group had a younger age of onset and lower Montreal Cognitive Assessment score than the GBA non-variant group in DLB patients. GBA variants do not differ between sexes in DLB patients. CONCLUSIONS: GBA variants increased the risk of DLB, especially N370S, E326K, and L444P which are strongly associated with DLB, but T369M was not. Patients harbouring GBA variants have an earlier age of onset, more severe cognitive impairment, and rapid symptom progression; however, sex is irrelevant in DLB.
OBJECTIVES: Glucocerebrosidase (GBA) gene may be a risk factor for dementia with Lewy bodies (DLB). However, due to the small number of existing studies and the small sample size of previous investigations, it is necessary to conduct objective and quantitative analyses of the association between GBA variants and DLB. There is no consensus regarding the relationship between GBA and the clinical characteristics of DLB. Therefore, we conducted multiple systematic reviews and meta-analyses with a particular focus on the age of onset, sex, and cognitive impairment. METHODS: PubMed, Cochrane, and EMBASE databases were searched to retrieve related studies. The odds ratios and 95% confidence interval were calculated to determine the association between GBA and DLB and between GBA and the clinical characteristics of DLB. RESULTS: Our meta-analysis confirmed that the GBA variant rate was significantly higher in the DLB group than in the control group, as were the variant rates of L444P, N370S, and E326K, whereas the variant rate of T369M showed no significant difference between the groups. Furthermore, the relevant literature was summarised again for meta-analyses. The GBA variant group had a younger age of onset and lower Montreal Cognitive Assessment score than the GBA non-variant group in DLB patients. GBA variants do not differ between sexes in DLB patients. CONCLUSIONS: GBA variants increased the risk of DLB, especially N370S, E326K, and L444P which are strongly associated with DLB, but T369M was not. Patients harbouring GBA variants have an earlier age of onset, more severe cognitive impairment, and rapid symptom progression; however, sex is irrelevant in DLB.
Authors: Brendon P Boot; Carolyn F Orr; J Eric Ahlskog; Tanis J Ferman; Rosebud Roberts; Vernon S Pankratz; Dennis W Dickson; Joseph Parisi; Jeremiah A Aakre; Yonas E Geda; David S Knopman; Ronald C Petersen; Bradley F Boeve Journal: Neurology Date: 2013-07-26 Impact factor: 9.910
Authors: Ian G McKeith; Bradley F Boeve; Dennis W Dickson; Glenda Halliday; John-Paul Taylor; Daniel Weintraub; Dag Aarsland; James Galvin; Johannes Attems; Clive G Ballard; Ashley Bayston; Thomas G Beach; Frédéric Blanc; Nicolaas Bohnen; Laura Bonanni; Jose Bras; Patrik Brundin; David Burn; Alice Chen-Plotkin; John E Duda; Omar El-Agnaf; Howard Feldman; Tanis J Ferman; Dominic Ffytche; Hiroshige Fujishiro; Douglas Galasko; Jennifer G Goldman; Stephen N Gomperts; Neill R Graff-Radford; Lawrence S Honig; Alex Iranzo; Kejal Kantarci; Daniel Kaufer; Walter Kukull; Virginia M Y Lee; James B Leverenz; Simon Lewis; Carol Lippa; Angela Lunde; Mario Masellis; Eliezer Masliah; Pamela McLean; Brit Mollenhauer; Thomas J Montine; Emilio Moreno; Etsuro Mori; Melissa Murray; John T O'Brien; Sotoshi Orimo; Ronald B Postuma; Shankar Ramaswamy; Owen A Ross; David P Salmon; Andrew Singleton; Angela Taylor; Alan Thomas; Pietro Tiraboschi; Jon B Toledo; John Q Trojanowski; Debby Tsuang; Zuzana Walker; Masahito Yamada; Kenji Kosaka Journal: Neurology Date: 2017-06-07 Impact factor: 9.910
Authors: Rita Guerreiro; Owen A Ross; Celia Kun-Rodrigues; Dena G Hernandez; Tatiana Orme; John D Eicher; Claire E Shepherd; Laura Parkkinen; Lee Darwent; Michael G Heckman; Sonja W Scholz; Juan C Troncoso; Olga Pletnikova; Olaf Ansorge; Jordi Clarimon; Alberto Lleo; Estrella Morenas-Rodriguez; Lorraine Clark; Lawrence S Honig; Karen Marder; Afina Lemstra; Ekaterina Rogaeva; Peter St George-Hyslop; Elisabet Londos; Henrik Zetterberg; Imelda Barber; Anne Braae; Kristelle Brown; Kevin Morgan; Claire Troakes; Safa Al-Sarraj; Tammaryn Lashley; Janice Holton; Yaroslau Compta; Vivianna Van Deerlin; Geidy E Serrano; Thomas G Beach; Suzanne Lesage; Douglas Galasko; Eliezer Masliah; Isabel Santana; Pau Pastor; Monica Diez-Fairen; Miquel Aguilar; Pentti J Tienari; Liisa Myllykangas; Minna Oinas; Tamas Revesz; Andrew Lees; Brad F Boeve; Ronald C Petersen; Tanis J Ferman; Valentina Escott-Price; Neill Graff-Radford; Nigel J Cairns; John C Morris; Stuart Pickering-Brown; David Mann; Glenda M Halliday; John Hardy; John Q Trojanowski; Dennis W Dickson; Andrew Singleton; David J Stone; Jose Bras Journal: Lancet Neurol Date: 2017-12-16 Impact factor: 44.182