Shu-Ying Liu1, Zheng Zheng2, Zhu-Qin Gu3, Chao-Dong Wang1, Bei-Sha Tang4, Yan-Ming Xu5, Jing-Hong Ma2, Yong-Tao Zhou2, Tao Feng6, Sheng-Di Chen7, Piu Chan8. 1. Department of Neurobiology, Neurology, and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, China; National Clinical Research Center for Geriatric Disorders, Beijing, China; 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. 2. Department of Neurobiology, Neurology, and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, China; National Clinical Research Center for Geriatric Disorders, Beijing, China. 3. Department of Neurobiology, Neurology, and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, China; 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. 4. Department of Neurology, Xiangya Hospital, Central South University, Changsha, China. 5. Department of Neurology, West China Hospital, Sichuan University, Chengdu, China. 6. Department of Neurology, Centre for Neurodegenerative Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 7. Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. 8. Department of Neurobiology, Neurology, and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, China; National Clinical Research Center for Geriatric Disorders, Beijing, China; 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. Electronic address: pbchan@hotmail.com.
Abstract
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.
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 LRRK2G2385R and R1628P variants and GBAL444P 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 PDpatients were recruited, including 226 patients with LRRK2G2385R or R1628P variant, 44 with GBAL444P 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.
Authors: Tanya Simuni; Liz Uribe; Hyunkeun Ryan Cho; Chelsea Caspell-Garcia; Christopher S Coffey; Andrew Siderowf; John Q Trojanowski; Leslie M Shaw; John Seibyl; Andrew Singleton; Arthur W Toga; Doug Galasko; Tatiana Foroud; Duygu Tosun; Kathleen Poston; Daniel Weintraub; Brit Mollenhauer; Caroline M Tanner; Karl Kieburtz; Lana M Chahine; Alyssa Reimer; Samantha J Hutten; Susan Bressman; Kenneth Marek Journal: Lancet Neurol Date: 2019-10-31 Impact factor: 44.182
Authors: Tanya Simuni; Michael C Brumm; Liz Uribe; Chelsea Caspell-Garcia; Christopher S Coffey; Andrew Siderowf; Roy N Alcalay; John Q Trojanowski; Leslie M Shaw; John Seibyl; Andrew Singleton; Arthur W Toga; Doug Galasko; Tatiana Foroud; Kelly Nudelman; Duygu Tosun-Turgut; Kathleen Poston; Daniel Weintraub; Brit Mollenhauer; Caroline M Tanner; Karl Kieburtz; Lana M Chahine; Alyssa Reimer; Samantha Hutten; Susan Bressman; Kenneth Marek Journal: Mov Disord Date: 2020-02-19 Impact factor: 10.338