机构：[a]Department of Neurobiology, Neurology, and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, China神经内科老年医学科首都医科大学宣武医院[b]National Clinical Research Center for Geriatric Disorders, Beijing, China[c]Key Laboratories of Ministry of Education for Neurodegenerative Diseases, Parkinson Disease Center of Beijing Institute for Brain Disorders, Beijing Key Laboratory on Parkinson's Disease, China[d]Department of Neurology, Xiangya Hospital, Central South University, Changsha, China[e]Department of Neurology, West China Hospital, Sichuan University, Chengdu, China[f]Department of Neurology, Centre for Neurodegenerative Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, China[g]Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China[h]The First Affiliated Hospital of Zhengzhou University, China[i]The Second Affiliated Hospital of Suzhou University, China[j]The Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, China[k]The Inner Mongolian People's Hospital, China[l]The Second Affiliated Hospital of Jilin University, China[m]The Second Affiliated Hospital of Zhejiang University, China[n]The First Affiliated Hospital of Dalian University, China[o]The Affiliated Hospital of Qindao University, China[p]The First Affiliated Hospital of Zhejiang University, China[q]The Affiliated Sir Run Run Shaw Hospital of Zhejiang University, China[r]The Affiliated Union Hospital of Tongji Medical College, Huazhong University of Science & Technology, China[s]Sichuan Provincial Rehabilitation Hospital, China[t]The First Hospital of Sun Yat-Sen University, China[u]Qilu Hospital of Shangdong University, China[v]The Affiliated Union University of Fujian Medical University, China[w]Beijing Hospital, China[x]Peking Union Medical College Hospital, China[y]The Affiliated Hospital of Xuzhou Medical College, China
Introduction: Glucocerebrosidase (GBA) mutations and leucine-rich repeat kinase 2 (LRRK2) variants are the most common genetic risk factors for late-onset Parkinson's disease (PD). In this study, we aimed to investigate the differences in pre-diagnostic symptoms of PD associated with the variants. Methods: The participants were recruited from 24 centers across China and genotyped for LRRK2 G2385R and R1628P variants and GBA L444P mutation. Participants were surveyed with structural questionnaires for history of environmental exposure and living habits and interviewed to collect the time at onset of each symptoms before diagnosis. We compared the cumulative prevalence and manifestation pattern of symptoms between groups using multiple logistic regression, adjusting age and gender. Results: Total 1799 PD patients were recruited, including 226 patients with LRRK2 G2385R or R1628P variant, 44 with GBA L444P mutation, three with both LRRK2 and GBA mutation, and 1526 idiopathic patients. The cumulative prevalence of non-motor and typical motor symptoms did not differ between groups before diagnosis (P > 0.05). The manifestation sequences of non-motor symptoms were indistinguishable between the LRRK2-carriers, GBA-carriers, and idiopathic PD subjects, and followed the sequence of constipation, hyposmia, sleep disorders, anxiety and depression, sexual dysfunction, urinary incontinency, dizziness and cognition. Slightly higher prevalence of hypomimia and micrographia were detected in the GBA-carriers. Conclusions: The prevalence of pre-diagnostic symptoms is almost indistinguishable between the LRRK2-carriers, GBA-carriers, and idiopathic PD before diagnosis; the sequence of the manifestation of non-motor symptoms largely conforms to the Braak stage for both genetic-related and idiopathic late-onset PD.
基金：
This work was supported by grants from the Beijing Municipal
Administration of Hospitals' Mission Plan (SML20150803), Beijing
Municipal Science and Technology Commission (Z161100000216140, Z171100000117013), Beijing Municipal commission of Health and
Family Planning (PXM2017_026283_000002), the Ministry of Science
and Technology (2016YFC1306003) and National Natural Science
Foundation (No.81771212).
第一作者机构：[a]Department of Neurobiology, Neurology, and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, China[b]National Clinical Research Center for Geriatric Disorders, Beijing, China[c]Key Laboratories of Ministry of Education for Neurodegenerative Diseases, Parkinson Disease Center of Beijing Institute for Brain Disorders, Beijing Key Laboratory on Parkinson's Disease, China
通讯作者：
通讯机构：[*]Department of Neurology, Neurobiology and Geriatrics, Xuanwu Hospital Capital Medical University, No. 45 Changchun Street, Beijing, 100053, China
推荐引用方式(GB/T 7714)：
Shu-Ying Liu,Zheng Zheng,Zhu-Qin Gu,et al.Prevalence of pre-diagnostic symptoms did not differ between LRRK2-related, GBA-related and idiopathic patients with Parkinson's disease[J].PARKINSONISM & RELATED DISORDERS.2018,57:doi:10.1016/j.parkreldis.2018.08.007.
APA：
Shu-Ying Liu,Zheng Zheng,Zhu-Qin Gu,Chao-Dong Wang,Bei-Sha Tang...&Xia Sheng.(2018).Prevalence of pre-diagnostic symptoms did not differ between LRRK2-related, GBA-related and idiopathic patients with Parkinson's disease.PARKINSONISM & RELATED DISORDERS,57,
MLA：
Shu-Ying Liu,et al."Prevalence of pre-diagnostic symptoms did not differ between LRRK2-related, GBA-related and idiopathic patients with Parkinson's disease".PARKINSONISM & RELATED DISORDERS 57.(2018)
