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Introduction: The interrelationship between neurocognitive impairments and motor functions was observed in patients with advanced Parkinson's disease (PD). This study was conducted to identify pre-operative neurocognitive and clinical predictors of short-term motor outcome following subthalamic nucleus deep brain stimulation (STN-DBS)., Methods: All consecutive PD patients who were eligible for bilateral STN-DBS from 2009 to 2019 were evaluated before and at 1 year following surgery. Standard motor evaluation and neurocognitive tests including global cognition, memory, executive functions (attention and category fluency), confrontational speech, visuospatial abilities, and mood were conducted at baseline. The post-operative STN-DBS effects were assessed at 1 year following the surgery. Multiple regression analysis was applied to identify baseline independent predictors of post-operative STN-DBS effect., Results: A total of 82 patients were analyzed. It was found that younger age at operation, higher levodopa responsiveness at baseline based on UPDRS-III total score, and better baseline verbal delayed memory and category fluency predicted post-operative motor outcome at 1 year following STN-DBS (F = 9.639, p < 0.001, R 2  = .340)., Conclusion: Our findings demonstrated the role of baseline cognitive burden, especially cognitive processes related to frontostriatal circuits, was significant clinical predictors of short-term motor outcomes following STN-DBS. Profile analysis of neurocognitive functions at baseline is recommended., (© 2022. Fondazione Società Italiana di Neurologia.)

A deeper understanding of the cross-cultural applicability of cognitive tests across countries and cultures is needed to better equip neuropsychologists for the assessment of patients from diverse backgrounds. Our study compared cognitive test scores in patients with advanced Parkinson's disease (PD) at the Prince of Wales Hospital ( n  = 63; Hong Kong) and the Foothills Medical Center ( n  = 20; Calgary, Canada). The groups did not differ in age or sex ( p  > .05), but Western patients had significantly more years of education ( M  = 14.2, SD  = 2.7) than Asian patients ( M  = 10.33, SD  = 4.4). Cognitive tests administered to both groups included: digit span, verbal fluency (animals), the Boston Naming Test, and verbal memory (California Verbal Learning Test or Chinese Auditory Verbal Learning Test). Testing was completed before and 12 months after deep brain stimulation surgery. Results showed cognitive performance was similar across time, but significant group differences were found on digit span forward (longer among patients from Hong Kong; F (1, 75) = 44.155, p  < .001) and the Boston Naming Test (higher percent spontaneous correct among patients from Canada; F (1, 62) = 7.218, p  = .009, η 2 = 0.104), after controlling for age, sex, and years of education. In conclusion, our findings provide preliminary support for the similarity of Chinese versions of tests originally developed for Western populations. Also, we caution that some aspects of testing may be susceptible to cultural bias and therefore warrant attention in clinical practice and refinement in future test development for Asian patients.

Objective: To investigate the prevalence and clinical correlates of video polysomnography (vPSG)-confirmed rapid eye movement sleep behaviour disorder (RBD) in patients with major depressive disorder (MDD)., Methods: This is a clinic-based two-phase epidemiological study. In phase 1, patients with MDD were screened by a validated questionnaire, RBD Questionnaire-Hong Kong (RBDQ-HK). In phase 2, a subsample of both the screen-positive (RBDQ-HK >20) and screen-negative patients with MDD underwent further clinical and sleep assessment (vPSG) to confirm the diagnosis of RBD (MDD+RBD). Poststratification weighting method was used to estimate the prevalence of MDD+RBD. The total likelihood ratio and the probability of prodromal Parkinson's disease (PD) were calculated from prodromal markers and risk factors, as per the Movement Disorder Society research criteria., Results: A total of 455 patients with MDD were screened (median age (IQR)=52.66 (15.35) years, 77.58% woman, 43.74% positive). Eighty-one patients underwent vPSG and 12 of them were confirmed MDD+RBD. The prevalence of MDD+RBD was estimated to be 8.77% (95% CI: 4.33% to 16.93%), with possibly male predominance. MDD+RBD were associated with colour vision and olfaction deficit and a higher probability for prodromal PD., Conclusions: Almost 9% of patients with MDD in the psychiatric outpatient clinic has vPSG-confirmed RBD. Comorbid MDD+RBD may represent a subtype of MDD with underlying α-synucleinopathy neurodegeneration. Systematic screening of RBD symptoms and necessity of vPSG confirmation should be highlighted for capturing this MDD subtype with a view to enhance personalised treatment and future neuroprotection to prevent neurodegeneration., Competing Interests: Competing interests: JW and BH were supported by the Faculty Postdoctoral Fellowship Scheme of the Chinese University of Hong Kong. The University reimbursed their registration fee and airfare for attending international academic conferences in 2019. YL was supported by the Postdoctoral Fellowship in Clinical Neurosciences of the Chinese University of Hong Kong. JWYC received personal fees from Eisai for joining an insomnia expert forum. YKW received personal fees from Eisai for lecture and travel support from Lundbeck HK, which are outside the submitted work., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The search for biomarkers of cognitive impairment in Parkinson's disease is driven by the potential clinical applications in disease prognostication. Various eye tracking studies on cognitive functions in Parkinson's disease suggest a promising role of eye movement parameters as a biomarker for cognitive decline but the clinical utility has not been validated in longitudinal studies. The present study aims to investigate the longitudinal progression of eye fixation duration in a visual search task and its correlation with domain-specific cognitive impairment., Method: This is a 2-year follow-up study on a group of non-demented Parkinson's disease patients, with baseline eye movement metrics and multi-domain cognitive functions measured, to assess the association between domain-specific cognitive impairment and progression of visual fixation duration., Results: A total of 49 from the original 62 non-demented Parkinson's disease patients were re-examined at a 2-year follow-up. 15 cases (31%) were classified as having mild cognitive impairment. Visual fixation duration was significantly prolonged after 2 years. Using repeated measures ANOVA, impairment in semantic verbal fluency, visual and verbal recognition memory and orienting function of attention had a significant effect on prolonging visual fixation over time., Conclusion: Correlation between prolonged visual fixation and multiple domains of cognitive impairment related to cholinergic dysfunction in repeated measures over two years provides preliminary evidence for the eye tracking paradigm as a surrogate marker for cholinergic deficit in Parkinson's disease. The clinical utility in terms of disease prognostication is yet to be confirmed in prospective longitudinal studies with longer follow-up periods., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Importance: Large-scale genome-wide association studies in the European population have identified 90 risk variants associated with Parkinson disease (PD); however, there are limited studies in the largest population worldwide (ie, Asian)., Objectives: To identify novel genome-wide significant loci for PD in Asian individuals and to compare genetic risk between Asian and European cohorts., Design Setting, and Participants: Genome-wide association data generated from PD cases and controls in an Asian population (ie, Singapore/Malaysia, Hong Kong, Taiwan, mainland China, and South Korea) were collected from January 1, 2016, to December 31, 2018, as part of an ongoing study. Results were combined with inverse variance meta-analysis, and replication of top loci in European and Japanese samples was performed. Discovery samples of 31 575 individuals passing quality control of 35 994 recruited were used, with a greater than 90% participation rate. A replication cohort of 1 926 361 European-ancestry and 3509 Japanese samples was analyzed. Parkinson disease was diagnosed using UK Parkinson's Disease Society Brain Bank Criteria., Main Outcomes and Measures: Genotypes of common variants, association with disease status, and polygenic risk scores., Results: Of 31 575 samples identified, 6724 PD cases (mean [SD] age, 64.3 [10] years; age at onset, 58.8 [10.6] years; 3472 [53.2%] men) and 24 851 controls (age, 59.4 [11.4] years; 11 030 [45.0%] men) were analyzed in the discovery study. Eleven genome-wide significant loci were identified; 2 of these loci were novel (SV2C and WBSCR17) and 9 were previously found in Europeans. Replication in European-ancestry and Japanese samples showed robust association for SV2C (rs246814; odds ratio, 1.16; 95% CI, 1.11-1.21; P = 1.17 × 10-10 in meta-analysis of discovery and replication samples) but showed potential genetic heterogeneity at WBSCR17 (rs9638616; I2=67.1%; P = 3.40 × 10-3 for hetereogeneity). Polygenic risk score models including variants at these 11 loci were associated with a significant improvement in area under the curve over the model based on 78 European loci alone (63.1% vs 60.2%; P = 6.81 × 10-12)., Conclusions and Relevance: This study identified 2 apparently novel gene loci and found 9 previously identified European loci to be associated with PD in this large, meta-genome-wide association study in a worldwide population of Asian individuals and reports similarities and differences in genetic risk factors between Asian and European individuals in the risk for PD. These findings may lead to improved stratification of Asian patients and controls based on polygenic risk scores. Our findings have potential academic and clinical importance for risk stratification and precision medicine in Asia.

Recent whole-exome sequencing studies in European patients with Parkinson's disease (PD) have identified potential risk variants across 33 novel PD candidate genes. We aim to determine if these reported candidate genes are similarly implicated in Asians by assessing common, rare, and novel nonsynonymous coding variants by sequencing all 33 genes in 198 Chinese samples and genotyping coding variants in an independent set of 9756 Chinese samples. We carried out further targeted sequencing of CD36 in an additional 576 Chinese and Korean samples. We found that only 8 of 43 reported risk variants were polymorphic in our Chinese samples. We identified several heterozygotes for rare loss-of-function mutations, including the reported CD36 p.Gln74Ter variant, in both cases and controls. We also observed 2 potential compound heterozygotes among PD cases for rare loss-of-function mutations in CD36 and SSPO. The other reported variants were common in East Asians and not associated with PD, completely absent, or only found in controls. Therefore, the 33 reported candidate genes and associated variants are unlikely to confer significant PD risk in the East Asian population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical treatment for Parkinson's disease (PD). However, there is currently no consensus on the best timing for this surgery. The aim of our study is to compare the therapeutic efficacy of bilateral STN DBS in patients with PD with early and late motor complications., Methods and Analysis: 200 patients with PD will be enrolled in this multicentre, prospective, observational study, and will be followed up for 4 years. Patients with PD who meet the criteria for STN DBS surgery will be allocated to either the early stimulation group or the late stimulation group based on the duration of their motor complications. The primary outcome will be changes in quality of life from baseline to 4 years, measured using the 39-item Parkinson's Disease Questionnaire Summary Index. The secondary outcomes include changes in motor function measured using Movement Disorder Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, self-reported experiences of daily living measured using MDS-UPDRS Part I B and Part II, good 'on' time recorded by the patients using a diary and safety profile of both groups., Ethics and Dissemination: The study received ethical approval from the Medical Ethical Committee of the First Affiliated Hospital, Sun Yat-sen University. The results of this study will be published in peer-reviewed journals and presented at international conferences., Trial Registration Number: NCT01922388; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Genome-wide association studies (GWAS) on Parkinson's disease (PD) have mostly been done in Europeans and Japanese. No study has been done in Han Chinese, which make up nearly a fifth of the world population. We conducted the first Han Chinese GWAS analysing a total of 22,729 subjects (5,125 PD cases and 17,604 controls) from Singapore, Hong Kong, Malaysia, Korea, mainland China and Taiwan. We performed imputation, merging and logistic regression analyses of 2,402,394 SNPs passing quality control filters in 779 PD cases, 13,227 controls, adjusted for the first three principal components. 90 SNPs with association P < 10-4 were validated in 9 additional sample collections and the results were combined using fixed-effects inverse-variance meta-analysis. We observed strong associations reaching genome-wide significance at SNCA, LRRK2 and MCCC1, confirming their important roles in both European and Asian PD. We also identified significant (P < 0.05) associations at 5 loci (DLG2, SIPA1L2, STK39, VPS13C and RIT2), and observed the same direction of associations at 9 other loci including BST1 and PARK16. Allelic heterogeneity was observed at LRRK2 while European risk SNPs at 6 other loci including MAPT and GBA-SYT11 were non-polymorphic or very rare in our cohort. Overall, we replicate associations at SNCA, LRRK2, MCCC1 and 14 other European PD loci but did not identify Asian-specific loci with large effects (OR > 1.45) on PD risk. Our results also demonstrate some differences in the genetic contribution to PD between Europeans and Asians. Further pan-ethnic meta-analysis with European GWAS cohorts may unravel new PD loci., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A recent study MacLeod et al. has shown that an interaction between variants at the LRRK2 and PARK16 loci influences risk of development of Parkinson's disease (PD). Our study examines the proposed interaction between LRRK2 and PARK16 variants in modifying PD risk using a large multicenter series of PD patients (7715) and controls (8261) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Our data does not support a strong direct interaction between LRRK2 and PARK16 variants; however, given the role of retromer and lysosomal pathways in PD, further studies are warranted., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD)., Methods: We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations., Results: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci., Conclusions: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD., (© 2015 American Academy of Neurology.)

To evaluate the contribution of non-synonymous-coding variants of known familial and genome-wide association studies (GWAS)-linked genes for Parkinson's disease (PD) to PD risk in the East Asian population, we sequenced all the coding exons of 39 PD-related disease genes and evaluated the accumulation of rare non-synonymous-coding variants in 375 early-onset PD cases and 399 controls. We also genotyped 782 non-synonymous-coding variants of these genes in 710 late-onset PD cases and 9046 population controls. Significant enrichment of LRRK2 variants was observed in both early- and late-onset PD (odds ratio = 1.58; 95% confidence interval = 1.29-1.93; P = 8.05 × 10(-6)). Moderate enrichment was also observed in FGF20, MCCC1, GBA and ITGA8. Half of the rare variants anticipated to cause loss of function of these genes were present in healthy controls. Overall, non-synonymous-coding variants of known familial and GWAS-linked genes appear to make a limited contribution to PD risk, suggesting that clinical sequencing of these genes will provide limited information for risk prediction and molecular diagnosis., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Two recent studies identified a mutation (p.Asp620Asn) in the vacuolar protein sorting 35 gene as a cause for an autosomal dominant form of Parkinson disease . Although additional missense variants were described, their pathogenic role yet remains inconclusive., Methods and Results: We performed the largest multi-center study to ascertain the frequency and pathogenicity of the reported vacuolar protein sorting 35 gene variants in more than 15,000 individuals worldwide. p.Asp620Asn was detected in 5 familial and 2 sporadic PD cases and not in healthy controls, p.Leu774Met in 6 cases and 1 control, p.Gly51Ser in 3 cases and 2 controls. Overall analyses did not reveal any significant increased risk for p.Leu774Met and p.Gly51Ser in our cohort., Conclusions: Our study apart from identifying the p.Asp620Asn variant in familial cases also identified it in idiopathic Parkinson disease cases, and thus provides genetic evidence for a role of p.Asp620Asn in Parkinson disease in different populations worldwide.

Objective: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown., Methods: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry., Results: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78-0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14-1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I(2) estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD., Conclusion: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity.

Objective: The 10 year outcomes and impact of motor and non-motor features on survival of a cohort of new onset Chinese Parkinson's disease (PD) patients were prospectively studied., Method: A cohort of new onset PD patients from 1995 to 2002 was recruited from a regional hospital based movement disorder clinic. Subjects were classified into postural instability gait disorder (PIGD), tremor predominant type or mixed subtypes at presentation. All were evaluated yearly for development of sensory complaints, first significant fall, hallucinations, dementia, postural hypotension, speech disturbances, dysphagia and postural instability persisted during 'on' medication state (PIPon). Mortality and predictors of death were determined., Results: 171 new onset PD patients were recruited. After a mean follow-up of 11.3±2.6 years, 50 (29%) patients died. The standardised mortality ratio was 1.1 (CI 0.8 to 1.5, p=0.34). 83 (49%) developed dementia, 81 (47%) had psychosis and 103 (60%) had sensory complaints. Postural hypotension was found in 58 (34%) patients, 108 (63%) had PIPon, 101 (59%) had falls, 102 (60%) had dysphagia, 148 (87%) had freezing of gait and 117 (68%) had speech disturbances. 46 (27%) were institutionalised whereas 54 (32%) lived independently. Dementia (HR 5.0, 95% CI 2.1 to 13.0), PIPon (HR 2.8, 95% CI 1.2 to 6.8), older onset (HR 1.05, 1 year increase in age, 95% CI 1.0 to 1.1) and PIGD type (HR 2.1, 95% CI 1.2 to 3.7) were independent predictors of death., Conclusions: 10 years into PD, a significant proportion of patients developed dopa resistant motor and non-motor features. Older onset, PIGD type, PIPon and dementia had a negative impact on survival. Standardised mortality ratio was 1.1.

Objective: Development of wearing off (WO) often goes unnoticed for both patients with Parkinson's disease (PD) and physicians due to the complexity of this phenomenon. A brief 9-symptom WO questionnaire (WOQ-9) was recently found to be highly sensitive in its detection. We aimed to validate a Chinese version WOQ-9 (CWOQ-9) among Chinese patients with PD., Methods: We recruited 101 literate Chinese PD patients among 4 different neurology or movement disorders clinics in Hong Kong to participate in this study by completing the CWOQ-9. Clinical judgment by the specialists was considered the gold standard for diagnosing WO., Results: The mean age (±SD) of the patients was 61 (±9) years and 35 (34.7%) of them were female. The disease duration was 7.4 (±5.4) years and 69 (68.3%) of them were diagnosed clinically to have WO by the specialists. The positive and negative predictive values, sensitivity and specificity of CWOQ-9 were 86%, 71%, 87%, and 69% respectively. The area under curve (AUC) was 0.78 (p<0.001)., Conclusion: This simple patient questionnaire is a valid tool for the detection of WO among Chinese PD patients., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Preladenant is an adenosine 2A (A₂(A)) receptor antagonist. In animal models of Parkinson's disease, preladenant monotherapy improves motor function without causing dyskinesia and, as an adjunct to levodopa, it improves motor function without worsening dyskinesia. We aimed to assess the efficacy and safety of preladenant in patients with Parkinson's disease and motor fluctuations who were receiving levodopa and other antiparkinsonian drugs., Methods: In this phase 2, dose-finding trial, patients with Parkinson's disease who were receiving levodopa were enrolled and treated at 44 sites in 15 countries between December, 2006, and November, 2008. Assignment to treatment was done centrally with an interactive voice response system, according to a block randomisation schedule that was computer generated by the sponsor. Patients were assigned to receive 1, 2, 5, or 10 mg oral preladenant twice daily, or matching placebo for 12 weeks. Patients, study staff, investigators, and all sponsor personnel were masked to treatment assignment. The primary outcome was change in mean daily off time from baseline to week 12, as assessed by home diaries. Efficacy analysis included all patients who received at least one dose of study drug and had data for assessments after baseline. This trial is registered with ClinicalTrials.gov, number NCT00406029., Findings: 253 patients were randomised to receive preladenant (1 mg [n=49], 2 mg [n=49], 5 mg [n=49], 10 mg [n=57]) or placebo (n=49), of whom 234 on preladenant (1 mg [n=47], 2 mg [n=48], 5 mg [n=45], 10 mg [n=49]) and placebo (n=45) were eligible for the efficacy analysis. Mean daily off time from baseline to week 12 was reduced versus placebo in patients on 5 mg preladenant (difference -1·0 h, 95% CI -2·1 to 0·0; p=0·0486) and 10 mg preladenant (-1·2 h, -2·2 to -0·2; p=0·019). Changes in mean daily off time versus placebo were not significant for 1 mg preladenant (0·2 h, -0·9 to 1·2; p=0·753) or 2 mg preladenant (-0·7 h, -1·7 to 0·3; p=0·162). The most common adverse events in the combined preladenant group versus placebo were worsening of Parkinson's disease (22 [11%] vs 4 [9%]), somnolence (20 [10%] vs 3 [6%]), dyskinesia (18 [9%] vs 6 [13%]), nausea (17 [9%] vs 5 [11%]), constipation (15 [8%] vs 1 [2%]), and insomnia (15 [8%] vs 4 [9%])., Interpretation: 5 and 10 mg preladenant twice daily might be clinically useful to reduce off time in patients with Parkinson's disease and motor fluctuations., Funding: Schering-Plough, a subsidiary of Merck., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Although previous studies showed that patients with Parkinson's disease (PD) have low bone mineral density (BMD), there is little data on factors predisposing PD patients to low BMD. We compared the BMD of 108 PD patients (58 females) with an average age of 68 (range 42-83) years with that of 216 sex- and age-matched controls, adjusting for other covariate factors (exercise levels, estrogen status, dietary calcium intake, smoking, drinking, body mass index, and percentage of body fat). The mean BMD in the hip and lumbar spine of male PD patients did not differ significantly from those of male controls. On the other hand, the mean BMD in femoral neck was significantly lower in female PD patients than in controls (0.53 +/- 0.11 g/cm(2) versus 0.58 +/- 0.10 g/cm(2), P = 0.005). Compared with controls, female PD patients experienced menopause much earlier (47 years versus 50 years, P = 0.028). The percentage of body fat was also lower in female PD patients (33% versus 36%, P = 0.02). A lower BMD in the hip in female PD patients was associated with an increased number of months after menopause (P = 0.004) and lower percentage of body fat (P = 0.025). We concluded that female patients with PD have lower hip BMD, but this association appears largely attributable to differences in percentage body fat and years since menopause. After multivariate adjustment, PD no longer remained independently associated with reduced BMD in female patients.

The frequency of LRRK2 Gly2385Arg mutation in Hong Kong Chinese with early-onset (age < or =45 years) Parkinson's disease was identified and compared with late-onset patients (age >50 years) and controls. The mutation prevalence were 8.8, 8.3, and 0% for early-onset, late-onset, and controls, respectively. The mean age of onset among LRRK2 G2385R carriers was 42.7 years old for early-onset compared to 74.3 for late-onset patients. LRRK2 G2385R mutation appears to be as prevalent among early-onset as late-onset patients.

Our aim was to characterise PARK2 mutations and clinical features in Hong Kong Chinese with early-onset Parkinson's disease. Subjects were recruited from two major hospitals. Detailed data included demographics, age of onset, duration of disease, neurological manifestations, complications and disease severity. Genetic analysis for PARK2 mutations was performed. Thirty-four patients were recruited (mean age of onset = 39 years; mean duration of disease = 10 years). Seven patients reported a family history. The salient clinical manifestations were resting tremor (33/34), bradykinesia (33/34), rigidity (30/34), postural instability (20/34), good response to L-dopa (33/34), asymmetry at onset (31/34) and sleep benefit (12/34). Motor complications were reported in a significant number of patients, and depression was the most common nonmotor complication. Five patients were identified to have PARK2 mutations. Two sisters were compound heterozygotes for an insertion and a deletion, a novel and rare 1 bp insertion/nonsense mutation c1378&#95;1379insG (exon 12) and the entire deletion of exon 7. Another patient was homozygous for the entire deletion of exon 6. Two carriers were identified, one with a T1321C (Cys441Arg) missense mutation in exon 12 and another with a snp within intron 4. Our study reviewed a higher prevalence of PARK2 mutations in Chinese than that previously documented. A compound heterozygous mutation within two sisters with significant differences in age of onset and phenotypic manifestations suggest that modifier affects may be present in this family.

Objective: To review the aetiology, diagnosis, and management of Parkinson's disease, with a local perspective., Data Sources: Medline from 1966 onwards, and all major neurological journals and movement disorder journals were searched for evidence on the aetiology, diagnosis, and management of Parkinson's disease., Study Selection: Key words for the literature search were "Parkinson's disease" and "Chinese" or "Hong Kong"., Data Extraction: All relevant articles in English were reviewed., Data Synthesis: The number of promising genes for familial Parkinson's disease is still expanding rapidly and there has been a wealth of studies on susceptibility genes for Parkinson's disease. Potential treatment choices include the use of agents thought to be neuroprotective, symptomatic treatment with drugs or surgery, and non-pharmacological treatments. Pharmacological treatment using a dopa-sparing strategy and continuous dopaminergic stimulation is now gaining support to address the issue of long-term motor complications. Surgical treatment with deep brain stimulation is safe and effective for refractory cases and has been increasingly utilised locally., Conclusions: Medical therapy remains the mainstay of treatment and newer agents and treatment approaches are emerging, which will hopefully address the issue of neuroprotection and provide symptomatic treatment with fewer motor complications.

Objective: To evaluate the efficacy and safety of the non-ergot dopamine agonist pramipexole in untreated and levodopa-treated Chinese patients with early or advanced Parkinson's disease., Methods: This randomized, double-blind, placebo-controlled, parallel-group study, which was conducted in Hong Kong and Taiwan, comprised a screening period of at least 1 week, a dose-escalation period of 7 weeks, and a maintenance period of 8 weeks (total duration of treatment: 15 weeks). During the dose-escalation period, the dose of pramipexole (or number of placebo tablets) was escalated in a blinded fashion according to a predetermined schedule to the optimum tolerated dose of pramipexole, administered three times a day (minimum dose=0.375 mg/day; maximum dose=4.5 mg/day). This dose was then maintained for the duration of the maintenance period. Efficacy was primarily assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). Safety and tolerability were evaluated by treatment-emergent adverse event reports, clinical laboratory test results (blood chemistry, hematology, and urinalysis), vital signs, and electrocardiograms., Results: Pramipexole was significantly more effective than placebo in reducing the total scores of the UPDRS Part II, Part III, and Parts II and III combined. Approximately 70% of both the placebo- and pramipexole-treated patients evaluated in this analysis were on levodopa. Regardless of levodopa use, the mean UPDRS total scores showed a consistently greater improvement in pramipexole patients than in placebo patients. Mean scores for pramipexole patients not on levodopa showed a greater improvement than did pramipexole patients on levodopa. The mean improvement for the pramipexole/no levodopa group relative to the placebo/no levodopa group at week 15 was 10.93 points (i.e., -14.43 points minus -3.50 points). The mean improvement for the pramipexole/levodopa group relative to the placebo/levodopa group at week 15 was 9.04 points (i.e., -10.26 points minus -1.22 points). Pramipexole was also superior to placebo as measured by improvement in the modified Hoehn and Yahr Scale and a reduction in the number of "off" hours for patients on concomitant levodopa therapy., Conclusions: Pramipexole is an effective and well-tolerated therapy, with or without concomitant levodopa, for Chinese patients with Parkinson's disease.

Parkinson's disease is a progressive disabling movement disorder that is characterised by three cardinal symptoms: resting tremor, rigidity, and bradykinesia. Before the availability of effective medical treatment with levodopa and stereotactic neurosurgery, the objective of surgical management was to alleviate symptoms such as tremor at the expense of motor deficits. Levodopa was the first effective medical treatment for Parkinson's disease, and surgical treatment such as stereotactic thalamotomy became obsolete. After one decade of levodopa therapy, however, drug-induced dyskinesia had become a source of additional disability not amenable to medical treatment. Renewed interest in stereotactic functional neurosurgery to manage Parkinson's disease has been seen since the 1980s. Local experience of deep-brain stimulation is presented and discussed in this paper. Deep-brain stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson's disease, although evidence from randomised control trials is lacking.