Gut Microbial Ecosystem in Parkinson Disease: New Clinicobiological Insights from Multi-Omics.

OBJECTIVE: Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance. METHODS: Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry. RESULTS: Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR-based metabolome. Microbiome and NMR-based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N-oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability-gait disorder scores. INTERPRETATION: Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut-brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89:546-559.

Access and Attitudes Toward Palliative Care Among Movement Disorders Clinicians.

BACKGROUND: Neuropalliative care is an emerging field for those with neurodegenerative illnesses, but access to neuropalliative care remains limited. OBJECTIVE: We sought to determine Movement Disorder Society (MDS) members' attitudes and access to palliative care. METHODS: A quantitative and qualitative survey instrument was developed by the MDS Palliative Care Task Force and e-mailed to all members for completion. Descriptive statistics and qualitative analysis were triangulated. RESULTS: Of 6442 members contacted, 652 completed the survey. Completed surveys indicating country of the respondent overwhelmingly represented middle- and high-income countries. Government-funded homecare was available to 54% of respondents based on patient need, 25% limited access, and 21% during hospitalization or an acute defined event. Eighty-nine percent worked in multidisciplinary teams. The majority endorsed trigger-based referrals to palliative care (75.5%), while 24.5% indicated any time after diagnosis was appropriate. Although 66% referred patients to palliative care, 34% did not refer patients. Barriers were identified by 68% of respondents, the most significant being available workforce, financial support for palliative care, and perceived knowledge of palliative care physicians specific to movement disorders. Of 499 respondents indicating their training in palliative care or desire to learn these skills, 55% indicated a desire to gain more skills. CONCLUSIONS: The majority of MDS member respondents endorsed a role for palliative care in movement disorders. Many members have palliative training or collaborate with palliative care physicians. Although significant barriers exist to access palliative care, the desire to gain more skills and education on palliative care is an opportunity for professional development within the MDS. © 2021 International Parkinson and Movement Disorder Society.

Underrepresented Populations in Parkinson's Genetics Research: Current Landscape and Future Directions.

BACKGROUND: Human genetics research lacks diversity; over 80% of genome-wide association studies have been conducted on individuals of European ancestry. In addition to limiting insights regarding disease mechanisms, disproportionate representation can create disparities preventing equitable implementation of personalized medicine. OBJECTIVE: This systematic review provides an overview of research involving Parkinson's disease (PD) genetics in underrepresented populations (URP) and sets a baseline to measure the future impact of current efforts in those populations. METHODS: We searched PubMed and EMBASE until October 2021 using search strings for "PD," "genetics," the main "URP," and and the countries in Latin America, Caribbean, Africa, Asia, and Oceania (excluding Australia and New Zealand). Inclusion criteria were original studies, written in English, reporting genetic results on PD from non-European populations. Two levels of independent reviewers identified and extracted information. RESULTS: We observed imbalances in PD genetic studies among URPs. Asian participants from Greater China were described in the majority of the articles published (57%), but other populations were less well studied; for example, Blacks were represented in just 4.0% of the publications. Also, although idiopathic PD was more studied than monogenic forms of the disease, most studies analyzed a limited number of genetic variants. We identified just nine studies using a genome-wide approach published up to 2021, including URPs. CONCLUSION: This review provides insight into the significant lack of population diversity in PD research highlighting the immediate need for better representation. The Global Parkinson's Genetics Program (GP2) and similar initiatives aim to impact research in URPs, and the early metrics presented here can be used to measure progress in the field of PD genetics in the future. © 2022 International Parkinson and Movement Disorder Society.

Glucocerebrosidase (GBA) gene variants in a multi-ethnic Asian cohort with Parkinson's disease: mutational spectrum and clinical features.

GBA variants are associated with increased risk and earlier onset of Parkinson's disease (PD), and more rapid disease progression especially with "severe" variants typified by p.L483P. GBA mutation screening studies from South-East Asia, with > 650 million inhabitants of diverse ancestries, are very limited. We investigated the spectrum of GBA variants, and associated clinico-demographic features, in a multi-ethnic PD cohort in Malaysia. Patients (n = 496) were recruited from seven centres, primarily of Chinese (45%), Malay (37%), and Indian (13%) ethnicities. All GBA coding exons were screened using a next-generation sequencing-based PD gene panel and verified with Sanger sequencing. We identified 14 heterozygous GBA alleles consisting of altogether 17 missense variants (8 classified as pathogenic or likely pathogenic for PD) in 25 (5.0%) patients, with a substantially higher yield among early (< 50 years) vs. late-onset patients across all three ethnicities (9.1-13.2% vs. 1.0-3.2%). The most common variant was p.L483P (including RecNciI, n = 11, 2.2%), detected in all three ethnicities. Three novel variants/recombinant alleles of uncertain significance were found; p.P71L, p.L411P, and p.L15S(;)S16G(;)I20V. The common European risk variants, p.E365K, p.T408M, and p.N409S, were not detected. A severe disease course was noted in the majority of GBA-variant carriers, across a range of detected variants. We report a potentially novel observation of spine posture abnormalities in GBA-variant carriers. This represents the largest study on GBA variation from South-East Asia, and highlights that these populations, especially those with EOPD, would be relevant for studies including clinical trials targeting GBA pathways.

Association study of MCCC1/LAMP3 and DGKQ variants with Parkinson's disease in patients of Malay ancestry.

BACKGROUND: Genome-wide association studies (GWAS) have shown that variants in the 3-methylcrotonyl-CoA carboxylase (MCCC1)/lysosome-associated membrane protein 3 (LAMP3) loci (rs10513789, rs12637471, rs12493050) reduce the risk of Parkinson's disease (PD) in Caucasians, Chinese and Ashkenazi-Jews while the rs11248060 variant in the diacylglycerol kinase theta (DGKQ) gene increases the risk of PD in Caucasian and Han Chinese cohorts. However, their roles in Malays are unknown. Therefore, this study aims to investigate the association of these variants with the risk of PD in individuals of Malay ancestry. METHODS: A total of 1114 subjects comprising of 536 PD patients and 578 healthy controls of Malay ancestry were recruited and genotyped using Taqman® allelic discrimination assays. RESULTS: The G allele of rs10513789 (OR = 0.83, p = 0.001) and A allele of rs12637471 (OR = 0.79, p = 0.007) in the MCCC1/LAMP3 locus were associated with a protective effect against developing PD in the Malay population. A recessive model of penetrance showed a protective effect of the GG genotype for rs10513789 and the AA genotype for rs12637471. No association with PD was found with the other MCCC1/LAMP3 rs12493050 variant or with the DGKQ (rs11248060) variant. No significant associations were found between the four variants with the age at PD diagnosis. CONCLUSION: MCCC1/LAMP3 variants rs10513789 and rs12637471 protect against PD in the Malay population.

Osteoporosis in Parkinson's Disease: Relevance of Distal Radius Dual-Energy X-Ray Absorptiometry (DXA) and Sarcopenia.

Osteoporotic fractures are common in Parkinson's disease (PD). Standard dual-energy X-ray absorptiometry (DXA) measuring bone mineral density (BMD) at the femoral neck and lumbar spine (central sites) has suboptimal sensitivity in predicting fracture risk in the general population. An association between sarcopenia and osteoporosis in PD has not been studied. We compared BMD and osteoporosis prevalence in PD patients vs controls; determined the osteoporosis detection rates using central alone vs central plus distal radius DXA; and analyzed factors (in particular, sarcopenia) associated with osteoporosis. One hundred and fifty-six subjects (102 patients with PD, 54 spousal/sibling controls) underwent femoral neck-lumbar spine-distal radius DXA. Seventy-three patients and 46 controls were assessed for sarcopenia using whole-body DXA and handgrip strength. Patients underwent clinical and serum biochemical evaluations. PD patients had significantly lower body mass index compared to controls. After adjustment for possible confounders, distal radius BMD and T-scores were significantly lower in PD patients compared to controls, but not at the femoral neck/lumbar spine. With distal radius DXA, an additional 11.0% of patients were diagnosed with osteoporosis (32.0% to 43.0%), vs 3.7% in controls (33.3% to 37.0%) additionally diagnosed; this increase was largely driven by the markedly higher detection rate in female PD patients. Female gender (adjusted odds ratio [ORadjusted] = 11.3, 95% confidence interval [CI]: 2.6-48.6) and sarcopenia (ORadjusted = 8.4, 95% CI: 1.1-64.9) were independent predictors for osteoporosis in PD. Distal radius DXA increased osteoporosis detection, especially in female PD patients, suggesting that diagnostic protocols for osteoporosis in PD could be optimized. A close association between osteoporosis and sarcopenia was documented for the first time in PD, which has important implications for clinical management and future research.

Helicobacter pylori Eradication in Parkinson's Disease: A Randomized Placebo-Controlled Trial.

BACKGROUND: Helicobacter pylori (HP) infection has been associated with worse motor function in Parkinson's disease (PD). OBJECTIVE: We aimed to evaluate the effects of HP eradication on PD symptoms. METHODS: In this parallel-group, double-blind, randomized placebo-controlled, single-center trial, patients with PD with positive HP urea breath test and serology were block randomized (1:1) to receive standard eradication triple therapy or identically appearing placebo capsules for 1 week. Prespecified motor (International Parkinson and Movement Disorder Society Unified PD Rating Scale [MDS-UPDRS], timed tests, and home-based wearable sensor measurements), nonmotor (Leeds Dyspepsia Questionnaire and Montreal Cognitive Assessment), and quality-of-life (Parkinson's Disease Questionnaire-39) outcome measures were assessed at weeks 6, 12, 24, and 52. The primary outcome was the baseline-to-week 12 change in ON medication MDS-UPDRS motor scores. Lactulose-hydrogen breath testing for concomitant small intestinal bacterial overgrowth was performed at baseline and repeated at week 24, together with the urea breath test. RESULTS: A total of 310 patients were screened for eligibility and 80 were randomly assigned, of whom 67 were included in the full-analysis set (32 treatment group patients, 35 placebo patients). HP eradication did not improve MDS-UPDRS motor scores at week 12 (mean difference 2.6 points in favor of placebo, 95% confidence interval: -0.4 to 5.6, P = 0.089). There was no significant improvement in any motor, nonmotor, or quality-of-life outcome at weeks 12 and 52. Both the full-analysis and per-protocol analyses (based on eradication status) supported these conclusions. Small intestinal bacterial overgrowth status did not influence treatment results. CONCLUSIONS: HP eradication does not improve clinical outcomes in PD, suggesting that there is no justification for routine HP screening or eradication with the goal of improving PD symptoms. © 2020 International Parkinson and Movement Disorder Society.

Understanding patients' and caregivers' perspectives and educational needs in Parkinson's disease: a multi-ethnic Asian study.

INTRODUCTION: Little is known regarding the educational needs and perspectives of people living with Parkinson's disease (PD), particularly in Asia. OBJECTIVE: To assess knowledge and perceptions regarding PD in a large multiethnic urban Asian cohort of patients and caregivers. METHODS: We conducted a survey at a university hospital neurology clinic, using a novel Knowledge and Perception of Parkinson's Disease Questionnaire (KPPDQ). RESULTS: The KPPDQ had satisfactory psychometric properties among patients and caregivers. Five hundred subjects were recruited with a 97% response rate (211 patients, 273 caregivers). Non-motor symptoms such as urinary problems, visual hallucinations and pain were relatively poorly recognized. Many (≈ 50-80%) respondents incorrectly believed that all PD patients experience tremor, that PD is usually familial, and that there is a cure for PD. About one-half perceived PD to be caused by something the patient had done in the past, and that PD medications were likely to cause internal organ damage. Issues of stigma/shame were relevant to one-third of patients, and 70% of patients perceived themselves to be a burden to others. Two-thirds of participants felt that PD imposed a heavy financial toll. Participants were about equally divided as to whether they would consider treatment with deep brain stimulation, tube feeding or invasive ventilation. Over three-quarters of patients expressed a preference to die at home. CONCLUSIONS: Important knowledge gaps, misperceptions and perspectives on PD were identified, highlighting the need for further efforts to raise awareness and provide accurate information regarding PD, and to address patient's and caregivers' needs and preferences.

Clinical Phenotype of LRRK2 R1441C in 2 Chinese Sisters.

Pathogenic and risk variants in the LRRK2 gene are among the main genetic contributors to Parkinson's disease (PD) worldwide, and LRRK2-targeted therapies for patients with PARK-LRRK2are now entering clinical trials. However, in contrast to the LRRK2 G2019S mutation commonly found in Caucasians, North-African Arabs, and Ashkenazi Jews, relatively little is known about other causative LRRK2 mutations, and data on genotype-phenotype correlations are largely lacking. This report is from an ongoing multicentre study in which next-generation sequencing-based PD gene panel testing has so far been conducted on 499 PD patients of various ethnicities from Malaysia. We describe 2 sisters of Chinese ancestry with PD who carry the R1441C mutation in LRRK2 (which in Asians has been reported in only 2 Chinese patients previously), and highlight interesting clinical observations made over a decade of close follow-up. We further explored the feasibility of using a brief, expert-administered rating scale (the Clinical Impression of Severity Index; CISI-PD) to capture data on global disease severity in a large (n = 820) unselected cohort of PD patients, including severely disabled individuals typically excluded from research studies. All patients in this study were managed and evaluated by the same PD neurologist, and these data were used to make broad comparisons between the monogenic PD cases versus the overall "real world" PD cohort. This report contributes to the scarce literature on R1441C PARK-LRRK2, offering insights into natural history and epidemiological aspects, and provides support for the application of a simple and reliable clinical tool that can improve the inclusion of under-represented patient groups in PD research.

Genome-wide association study of Parkinson's disease in East Asians.

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.

Scales to assess impulsive and compulsive behaviors in Parkinson's disease: Critique and recommendations.

Impulse control disorders (ICDs) and related impulsive and compulsive behaviors (together called ICBs) have been increasingly recognized in the context of Parkinson's disease (PD) and treatment. The International Parkinson's and Movement Disorder Society commissioned a task force to assess available clinical screening instruments and rating scales, including their clinimetric properties, make recommendations regarding their utility, and suggest future directions in scale development and validation. The literature was systematically searched for scales measuring a range of reported ICBs in PD. A scale was designated "recommended" if the scale had been employed in PD studies, been used beyond the group that developed it, and had adequate clinimetric data published for PD. Numerous diagnostic screening tools and severity rating scales were identified for a range of ICBs, including compulsive medication use, punding/hobbyism, walkabout, pathological gambling, hypersexuality, compulsive or binge eating, compulsive buying, reckless driving, compulsive exercise, pyromania, trichotillomania, hoarding, kleptomania, intermittent explosive disorder, and internet addiction. For screening across the range of ICBs (except compulsive medication use), the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP) and QUIP-Rating Scale (QUIP-RS) are recommended, and for severity rating across the range of ICBs the QUIP-RS and the Ardouin Scale of Behavior in Parkinson's Disease are recommended. The Scale for Outcomes in Parkinson's Disease-Psychiatric Complications is recommended for rating of hypersexuality and the compulsive behaviors gambling/shopping. Further testing of established scales against gold standard diagnostic criteria is urgently required for all other individual ICBs in PD. © 2019 International Parkinson and Movement Disorder Society © 2019 International Parkinson and Movement Disorder Society.

International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson's disease.

OBJECTIVE: The objective of this review was to update evidence-based medicine recommendations for treating motor symptoms of Parkinson's disease (PD). BACKGROUND: The Movement Disorder Society Evidence-Based Medicine Committee recommendations for treatments of PD were first published in 2002 and updated in 2011, and we continued the review to December 31, 2016. METHODS: Level I studies of interventions for motor symptoms were reviewed. Criteria for inclusion and quality scoring were as previously reported. Five clinical indications were considered, and conclusions regarding the implications for clinical practice are reported. RESULTS: A total of 143 new studies qualified. There are no clinically useful interventions to prevent/delay disease progression. For monotherapy of early PD, nonergot dopamine agonists, oral levodopa preparations, selegiline, and rasagiline are clinically useful. For adjunct therapy in early/stable PD, nonergot dopamine agonists, rasagiline, and zonisamide are clinically useful. For adjunct therapy in optimized PD for general or specific motor symptoms including gait, rivastigmine is possibly useful and physiotherapy is clinically useful; exercise-based movement strategy training and formalized patterned exercises are possibly useful. There are no new studies and no changes in the conclusions for the prevention/delay of motor complications. For treating motor fluctuations, most nonergot dopamine agonists, pergolide, levodopa ER, levodopa intestinal infusion, entacapone, opicapone, rasagiline, zonisamide, safinamide, and bilateral STN and GPi DBS are clinically useful. For dyskinesia, amantadine, clozapine, and bilateral STN DBS and GPi DBS are clinically useful. CONCLUSIONS: The options for treating PD symptoms continues to expand. These recommendations allow the treating physician to determine which intervention to recommend to an individual patient. © 2018 International Parkinson and Movement Disorder Society.

Non-Motor Symptoms Assessed by Non-Motor Symptoms Questionnaire and Non-Motor Symptoms Scale in Parkinson's Disease in Selected Asian Populations.

BACKGROUND: Ethnic variations have been described in medical conditions, such as hypertension, diabetes, and multiple sclerosis. Whether ethnicity plays a role in Parkinson's disease (PD), particularly with regard to non-motor symptoms (NMS), remains unclear. Existing literature is diverse, controversial, and inadequately documented. This review aims to analyse and report the currently available literature on NMS, specifically in Asian PD patients. SUMMARY: We conducted a literature review using PubMed, searching for articles and currently available publications that reference and assess NMS in PD patients living in Asia using the validated NMS Questionnaire (NMS Quest) and NMS Scale (NMSS). In total, 24 articles were included: 12 using the NMS Quest and 12 using the NMSS. Symptoms of constipation, memory impairment, and nocturia were the most frequently self-reported symptoms (NMS Quest) in selected Asian populations, while symptoms within the domains sleep/fatigue, attention/memory, and mood/apathy were most prevalent when applying the health-professional completed NMSS. Key Messages: NMS are generally prevalent and highly burdensome within selected Asian PD populations living in countries included in this review. Our review suggests that NMS-driven phenotypic heterogeneity is present in Asian patients, and compared to Western PD populations there might be variations in assessed NMS.

Integrating Patient Concerns into Parkinson's Disease Management.

Parkinson's disease (PD) is a complex motor and non-motor disorder and management is often challenging. In this review, we explore emerging approaches to improve the care of patients, drawing from the literature regarding patient-centred care, patient and caregiver perspectives and priorities, gaps in knowledge among patients and caregivers and the need for accurate information, individual variability in disease manifestations, prognostication of disease course, new developments in health technologies and personalized medicine, specialty care, pharmacological and non-pharmacological management, financial burden, lifestyle and work-related issues, support groups and palliative care.

Analysis of non-synonymous-coding variants of Parkinson's disease-related pathogenic and susceptibility genes in East Asian populations.

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.

PARK16 is associated with PD in the Malaysian population.

PARK16 was identified as a risk factor for Parkinson's disease in a Japanese cohort; however, subsequent studies in the other populations including the Chinese, European, Caucasian, and Chilean have shown a protective role instead. To investigate this locus in our Malaysian cohort, 1,144 individuals were screened for five SNPs in the PARK16 locus and logistic regression analysis showed that the A allele of the rs947211 SNP reduced the risk of developing PD via a recessive model (Odds ratio 0.57, P-value 0.0003). Pooled analysis with other Asian studies showed that A allele of the rs947211 SNP decreased the risk of developing PD via a recessive model (Odds ratio 0.71, P-value 0.0001). In addition, when meta-analysis was performed with other Asian population, three SNPs (rs823128, rs823156, and rs11240572) reduced risk of developing PD via a dominant model. © 2016 Wiley Periodicals, Inc.

DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson's disease patients.

BACKGROUND: Impulse control disorder (ICD) and behaviours (ICB) represent a group of behavioural disorders that have become increasingly recognised in Parkinson's disease (PD) patients who previously used dopaminergic medications, particularly dopamine agonists and levodopa. It has been suggested that these medications can lead to the development of ICB through the abnormal modulation of dopaminergic transmission and signalling in the mesocorticolimbic dopaminergic system. Several studies have reported an association between polymorphisms in the dopamine receptor (DRD) and N-methyl-D-aspartate 2B (GRIN2B) genes with the development of ICB in PD (PD-ICB) patients. Thus, this study aimed to investigate the association of selected polymorphisms within the DRD and GRIN2B genes with the development of ICB among PD patients using high resolution melt (HRM) analysis. METHOD: We used high resolution melt (HRM) analysis to genotype 11 polymorphisms in 5 DRD genes [DRD1 (rs4532, rs4867798 and rs265981), DRD2 (ANKK1 rs1800497, rs104894220 and rs144999500), DRD3 (rs3732783 and rs6280), DRD4 (rs1800443), and DRD5 (rs144132215)] and 1 polymorphism in GRIN2B (rs7301328) in PD patients with (cases, n = 52) and without (controls, n = 39) ICB. Cases were obtained from two tertiary movement disorder centres [UKMMC (n = 9) and UMMC (n = 43)]. At both centres, the diagnosis of ICB was made using the QUIP questionnaire. Controls were recruited from PD patients who attended UKMMC and were found to be negative for ICB using the QUIP questionnaire. RESULTS: The HRM analysis showed that 7 of 11 polymorphisms [DRD1 (rs4532, rs4867798, and rs265981), DRD2 (ANKK1 rs1800497), DRD3 (rs3732783 and rs6280), and GRIN2B (rs7301328)] exhibited a clear distinction between wild-type and variant alleles. Variants of DRD2/ANKK1 rs1800497 (OR = 3.77; 95% CI, 1.38-10.30; p = 0.0044), DRD1 rs4867798 (OR = 24.53; 95% CI, 1.68-357.28; p = 0.0054), DRD1 rs4532 (OR = 21.33; 95% CI, 1.97-230.64; p = 0.0024), and GRIN2B rs7301328 (OR = 25.07; 95% CI, 1.30-483.41; p = 0.0097) were found to be associated with an increased risk of developing ICB among PD patients. CONCLUSION: Our findings suggest that polymorphisms in dopamine [DRD1 (rs4532 and rs4867798) and DRD2/ANKK1 rs1800497] and glutamate (GRIN2B rs7301328) receptor genes confer increased risk of ICB development among PD patients.

A coumarin-based fluorescent probe as a central nervous system disease biomarker.

Homocysteine and methylmalonic acid are important biomarkers for diseases associated with an impaired central nervous system (CNS). A new chemoassay utilizing coumarin-based fluorescent probe 1 to detect the levels of homocysteine is successfully implemented using Parkinson's disease (PD) patients' blood serum. In addition, a rapid identification of homocysteine and methylmalonic acid levels in blood serum of PD patients was also performed using the liquid chromatography-mass spectrometry (LC-MS). The results obtained from both analyses were in agreement. The new chemoassay utilizing coumarin-based fluorescent probe 1 offers a cost- and time-effective method to identify the biomarkers in CNS patients.