Displaying publications 101 - 120 of 169 in total

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  1. Fulltext DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson's disease patients
    Zainal Abidin S, Tan EL, Chan SC, Jaafar A, Lee AX, Abd Hamid MH, et al.
    BMC Neurol, 2015;15:59.
    PMID: 25896831 DOI: 10.1186/s12883-015-0316-2
    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.
    Matched MeSH terms: Parkinson Disease/complications; Parkinson Disease/genetics*
  2. Glycogen synthase kinase-3 beta (GSK-3β) signaling: Implications for Parkinson's disease
    Golpich M, Amini E, Hemmati F, Ibrahim NM, Rahmani B, Mohamed Z, et al.
    Pharmacol Res, 2015 Jul;97:16-26.
    PMID: 25829335 DOI: 10.1016/j.phrs.2015.03.010
    Glycogen synthase kinase 3 (GSK-3) dysregulation plays an important role in the pathogenesis of numerous disorders, affecting the central nervous system (CNS) encompassing both neuroinflammation and neurodegenerative diseases. Several lines of evidence have illustrated a key role of the GSK-3 and its cellular and molecular signaling cascades in the control of neuroinflammation. Glycogen synthase kinase 3 beta (GSK-3β), one of the GSK-3 isomers, plays a major role in neuronal apoptosis and its inhibition decreases expression of alpha-Synuclein (α-Synuclein), which make this kinase an attractive therapeutic target for neurodegenerative disorders. Parkinson's disease (PD) is a chronic neurodegenerative movement disorder characterized by the progressive and massive loss of dopaminergic neurons by neuronal apoptosis in the substantia nigra pars compacta and depletion of dopamine in the striatum, which lead to pathological and clinical abnormalities. Thus, understanding the role of GSK-3β in PD will enhance our knowledge of the basic mechanisms underlying the pathogenesis of this disorder and facilitate the identification of new therapeutic avenues. In recent years, GSK-3β has been shown to play essential roles in modulating a variety of cellular functions, which have prompted efforts to develop GSK-3β inhibitors as therapeutics. In this review, we summarize GSK-3 signaling pathways and its association with neuroinflammation. Moreover, we highlight the interaction between GSK-3β and several cellular processes involved in the pathogenesis of PD, including the accumulation of α-Synuclein aggregates, oxidative stress and mitochondrial dysfunction. Finally, we discuss about GSK-3β inhibitors as a potential therapeutic strategy in PD.
    Matched MeSH terms: Parkinson Disease/drug therapy*; Parkinson Disease/enzymology*
  3. Comparison of posterior subthalamic area deep brain stimulation for tremor using conventional landmarks versus directly targeting the dentatorubrothalamic tract with tractography
    Low HL, Ismail MNBM, Taqvi A, Deeb J, Fuller C, Misbahuddin A
    Clin Neurol Neurosurg, 2019 Oct;185:105466.
    PMID: 31466022 DOI: 10.1016/j.clineuro.2019.105466
    OBJECTIVE: To compare posterior subthalamic area deep brain stimulation (PSA-DBS) performed in the conventional manner against diffusion tensor imaging and tractography (DTIT)-guided lead implantation into the dentatorubrothalamic tract (DRTT).

    PATIENTS AND METHODS: Double-blind, randomised study involving 34 patients with either tremor-dominant Parkinson's disease or essential tremor. Patients were randomised to Group A (DBS leads inserted using conventional landmarks) or Group B (leads guided into the DRTT using DTIT). Tremor (Fahn-Tolosa-Marin) and quality-of-life (PDQ-39) scores were evaluated 0-, 6-, 12-, 36- and 60-months after surgery.

    RESULTS: PSA-DBS resulted in marked tremor reduction in both groups. However, Group B patients had significantly better arm tremor control (especially control of intention tremor), increased mobility and activities of daily living, reduced social stigma and need for social support as well as lower stimulation amplitudes and pulse widths compared to Group A patients. The better outcomes were sustained for up to 60-months from surgery. The active contacts of Group B patients were consistently closer to the centre of the DRTT than in Group A. Speech problems were more common in Group A patients.

    CONCLUSION: DTIT-guided lead placement results in better and more stable tremor control and fewer adverse effects compared to lead placement in the conventional manner. This is because DTIT-guidance allows closer and more consistent placement of leads to the centre of the DRTT than conventional methods.

    Matched MeSH terms: Parkinson Disease/physiopathology; Parkinson Disease/therapy*
  4. Fulltext Deciduous DPSCs Ameliorate MPTP-Mediated Neurotoxicity, Sensorimotor Coordination and Olfactory Function in Parkinsonian Mice
    Simon C, Gan QF, Kathivaloo P, Mohamad NA, Dhamodharan J, Krishnan A, et al.
    Int J Mol Sci, 2019 Jan 29;20(3).
    PMID: 30699944 DOI: 10.3390/ijms20030568
    Parkinson's disease (PD) is a neurodegenerative disorder defined by progressive deterioration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Dental pulp stem cells (DPSCs) have been proposed to replace the degenerated dopaminergic neurons due to its inherent neurogenic and regenerative potential. However, the effective delivery and homing of DPSCs within the lesioned brain has been one of the many obstacles faced in cell-based therapy of neurodegenerative disorders. We hypothesized that DPSCs, delivered intranasally, could circumvent these challenges. In the present study, we investigated the therapeutic efficacy of intranasally administered DPSCs in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Human deciduous DPSCs were cultured, pre-labelled with PKH 26, and intranasally delivered into PD mice following MPTP treatment. Behavioural analyses were performed to measure olfactory function and sensorimotor coordination, while tyrosine hydroxylase (TH) immunofluorescence was used to evaluate MPTP neurotoxicity in SNpc neurons. Upon intranasal delivery, degenerated TH-positive neurons were ameliorated, while deterioration in behavioural performances was significantly enhanced. Thus, the intranasal approach enriched cell delivery to the brain, optimizing its therapeutic potential through its efficacious delivery and protection against dopaminergic neuron degeneration.
    Matched MeSH terms: Parkinson Disease/metabolism; Parkinson Disease/therapy*
  5. Levodopa-induced myocardial infarction in a patient with Parkinson's disease and severe coronary artery disease
    Ng CF, Tiau PW, Tan HJ, Norlinah MI
    J R Coll Physicians Edinb, 2019 Mar;49(1):37-39.
    PMID: 30838990 DOI: 10.4997/JRCPE.2019.108
    Levodopa is the most effective medical treatment for Parkinson's disease (PD) to date. As dopamine is known to increase cardiac inotropism and vasomotor tone, peripheral dopamine decarboxylase inhibitor is coadministered to suppress the peripheral conversion of levodopa to dopamine. Levodopa poses potential cardiovascular risks, thus its use in patients with existing coronary artery disease needs to be carefully monitored. We report a case of an elderly male with newly diagnosed PD who developed non-ST-elevation myocardial infarction following levodopa (Madopar) initiation.
    Matched MeSH terms: Parkinson Disease/complications; Parkinson Disease/drug therapy*
  6. Fulltext Multi-strain probiotics (Hexbio) containing MCP BCMC strains improved constipation and gut motility in Parkinson's disease: A randomised controlled trial
    Ibrahim A, Ali RAR, Manaf MRA, Ahmad N, Tajurruddin FW, Qin WZ, et al.
    PLoS One, 2020;15(12):e0244680.
    PMID: 33382780 DOI: 10.1371/journal.pone.0244680
    OBJECTIVE: We determined the effectiveness of a multi-strain probiotic (Hexbio®) containing microbial cell preparation MCP®BCMC® on constipation symptoms and gut motility in PD patients with constipation.

    METHODS: PD patients with constipation (ROME III criteria) were randomized to receive a multi-strain probiotic (Lactobacillus sp and Bifidobacterium sp at 30 X 109 CFU) with fructo-oligosaccaride or placebo (fermented milk) twice daily for 8 weeks. Primary outcomes were changes in the presence of constipation symptoms using 9 items of Garrigues Questionnaire (GQ), which included an item on bowel opening frequency. Secondary outcomes were gut transit time (GTT), quality of life (PDQ39-SI), motor (MDS-UPDRS) and non-motor symptoms (NMSS).

    RESULTS: Of 55 recruited, 48 patients completed the study: 22 received probiotic and 26 received placebo. At 8 weeks, there was a significantly higher mean weekly BOF in the probiotic group compared to placebo [SD 4.18 (1.44) vs SD 2.81(1.06); (mean difference 1.37, 95% CI 0.68, 2.07, uncorrected p<0.001)]. Patients in the probiotic group reported five times higher odds (odds ratio = 5.48, 95% CI 1.57, 19.12, uncorrected p = 0.008) for having higher BOF (< 3 to 3-5 to >5 times/week) compared to the placebo group. The GTT in the probiotic group [77.32 (SD55.35) hours] reduced significantly compared to placebo [113.54 (SD 61.54) hours]; mean difference -36.22, 95% CI -68.90, -3.54, uncorrected p = 0.030). The mean change in GTT was 58.04 (SD59.04) hour vs 20.73 (SD60.48) hours respectively (mean difference 37.32, 95% CI 4.00, 70.63, uncorrected p = 0.028). No between-groups differences were observed in the NMSS, PDQ39-SI, MDS-UPDRS II and MDS-UPDRS III scores. Four patients in the probiotics group experienced mild reversible side effects.

    CONCLUSION: This study showed that consumption of a multi-strain probiotic (Hexbio®) over 8 weeks improved bowel opening frequency and whole gut transit time in PD patients with constipation.

    Matched MeSH terms: Parkinson Disease/complications; Parkinson Disease/physiopathology*
  7. Fulltext Edible bird's nest ameliorates oxidative stress-induced apoptosis in SH-SY5Y human neuroblastoma cells
    Yew MY, Koh RY, Chye SM, Othman I, Ng KY
    BMC Complement Altern Med, 2014;14:391.
    PMID: 25308934 DOI: 10.1186/1472-6882-14-391
    Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting the senile population with manifestation of motor disability and cognitive impairment. Reactive oxygen species (ROS) is implicated in the progression of oxidative stress-related apoptosis and cell death of the midbrain dopaminergic neurons. Its interplay with mitochondrial functionality constitutes an important aspect of neuronal survival in the perspective of PD. Edible bird's nest (EBN) is an animal-derived natural food product made of saliva secreted by swiftlets from the Aerodamus genus. It contains bioactive compounds which might confer neuroprotective effects to the neurons. Hence this study aims to investigate the neuroprotective effect of EBN extracts in the neurotoxin-induced in vitro PD model.
    Matched MeSH terms: Parkinson Disease/drug therapy; Parkinson Disease/metabolism*; Parkinson Disease/physiopathology
  8. Gamma knife thalamotomy for disabling tremor: a blinded evaluation
    Lim SY, Hodaie M, Fallis M, Poon YY, Mazzella F, Moro E
    Arch. Neurol., 2010 May;67(5):584-8.
    PMID: 20457958 DOI: 10.1001/archneurol.2010.69
    Gamma knife thalamotomy (GKT) has been used as a therapeutic option for patients with disabling tremor refractory to medications. Impressive improvement of tremor has been reported in the neurosurgical literature, but the reliability of such data has been questioned.
    Matched MeSH terms: Parkinson Disease/pathology; Parkinson Disease/physiopathology; Parkinson Disease/surgery*
  9. Fulltext The Association Between Bullous Pemphigoid and Neurological Disorders in A Selected Malaysian Population
    Kwan Z, Lai YN, Ch'ng CC, Tan AH, Tan LL, Robinson S, et al.
    Med J Malaysia, 2015 Apr;70(2):81-5.
    PMID: 26162382 MyJurnal
    BACKGROUND: An association of bullous pemphigoid with neurological disorders has been reported. The objectives of this study were to review the clinical characteristics of patients with bullous pemphigoid and compare the association between bullous pemphigoid and various neurological disorders and comorbidities.

    METHODS: This was a retrospective case-control study involving 43 patients with bullous pemphigoid and 43 age-, sex- and ethnicity-matched controls.

    RESULTS: There was a statistically significant association between bullous pemphigoid and neurological disorders [Odds Ratio (OR) = 3.5, 95% Confidence Interval (CI) 1.3 to 9.2, p=0.011 and adjusted OR=3.5, 95% CI 1.2-10.3, p=0.026], in particular for dementia (p=0.002). Although stroke was more common among patients with bullous pemphigoid, this association was not statistically significant with OR of 1.9 (95% CI 0.7 to 5.2) and adjusted OR of 2.1 (95% CI 0.6 to 7.2). Similarly both ischaemic stroke (OR 1.5, 95% CI 0.5 to 4.2) and haemorrhagic stroke (OR 1.5, 95% CI 0.2 to 9.7) were more common. Other neurological disorders more common among patients with bullous pemphigoid were Parkinson's disease and epilepsy. Dyslipidaemia was significantly less common among patients with bullous pemphigoid (OR 0.4, 95% CI 0.1 to 0.9, p=0.033).

    CONCLUSION: A combination of an inflammatory process, prothrombotic state and endothelial activation leads to an increased frequency of neurological disorders among patients with bullous pemphigoid. Thus, a holistic approach to patient care, including screening for dementia and control of comorbidities, should be practised as bullous pemphigoid affects more than just the skin.
    Matched MeSH terms: Parkinson Disease
  10. Fulltext Examination Standards for Disabled Driver's Licensing
    Citation: Examination Standards for Disabled Driver's Licensing. Putrajaya: Occupational Health Unit, Disease Control Division, Ministry of Health Malaysia; 2011
    Matched MeSH terms: Parkinson Disease
  11. Exploring bedside clinical features of parkinsonism: A focus on differential diagnosis
    Bhidayasiri R, Rattanachaisit W, Phokaewvarangkul O, Lim TT, Fernandez HH
    Parkinsonism Relat Disord, 2019 Feb;59:74-81.
    PMID: 30502095 DOI: 10.1016/j.parkreldis.2018.11.005
    The proper diagnosis of parkinsonian disorders usually involves three steps: identifying core features of parkinsonism; excluding other causes; and collating supportive evidence based on clinical signs or investigations. While the recognition of cardinal parkinsonian features is usually straightforward, the appreciation of clinical features suggestive of specific parkinsonian disorders can be challenging, and often requires greater experience and skills. In this review, we outline the clinical features that are relevant to the differential diagnosis of common neurodegenerative parkinsonian disorders, including Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. We aim to make this process relatable to clinicians-in-practice, therefore, have categorised the list of clinical features into groups according to the typical sequence on how clinicians would elicit them during the examination, starting with observation of facial expression and clinical signs of the face, spotting eye movement abnormalities, examination of tremors and jerky limb movements, and finally, examination of posture and gait dysfunction. This review is not intended to be comprehensive. Rather, we have focused on the most common clinical signs that are potentially key to making the correct diagnosis and those that do not require special skills or training for interpretation. Evidence is also provided, where available, such as diagnostic criteria, consensus statements, clinicopathological studies or large multi-centre registries. Pitfalls are also discussed when relevant to the diagnosis. While no clinical signs are pathognomonic for certain parkinsonian disorders, certain clinical clues may assist in narrowing a differential diagnosis and tailoring focused investigations for the individual patient.
    Matched MeSH terms: Parkinson Disease
  12. Distinguishing normal and aggregated alpha-synuclein interaction on gold nanorod incorporated zinc oxide nanocomposite by electrochemical technique
    Adam H, Gopinath SCB, Arshad MKM, Parmin NA, Hashim U
    Int J Biol Macromol, 2021 Feb 28;171:217-224.
    PMID: 33418041 DOI: 10.1016/j.ijbiomac.2021.01.014
    Misfolding and accumulation of the protein alpha synuclein in the brain cells characterize Parkinson's disease (PD). Electrochemical based aluminum interdigitated electrodes (ALIDEs) was fabricated by using conventional photolithography method and modified the surfaces with zinc oxide and gold nanorod by using spin coating method for the analysis of PD protein biomarker. The device surface modified with gold nanorod of 25 nm diameter was used. The bare devices and the surface modified devices were characterized by Scanning Electron Microscope, 3D-Profilometer, Atomic Force Microscope and high-power microscope. The above measurement was also performed to measure the interaction of antibody with aggregated alpha-synuclein for normal, aggregated and aggregated alpha synuclein in human serum and distinguished against 3 control proteins (PARK1, DJ-1 and Factor IX). The detection limit for normal alpha synuclein was 1 f. with the sensitivity of 1 f. on a linear regression (R2 = 0.9759). The detection limit for aggregated alpha synuclein was 10 aM with the sensitivity of 1 aM on a linear regression (R2 = 0.9797). Also, the detection limit of aggregated alpha synuclein in serum was 10 aM with the sensitivity of 1 aM on a linear regression (R2 = 0.9739). These results however indicate that, serum has only minimal amount of alpha synuclein.
    Matched MeSH terms: Parkinson Disease
  13. Sirtuins and Their Implications in Neurodegenerative Diseases from a Drug Discovery Perspective
    Yeong KY, Berdigaliyev N, Chang Y
    ACS Chem Neurosci, 2020 12 16;11(24):4073-4091.
    PMID: 33280374 DOI: 10.1021/acschemneuro.0c00696
    Sirtuins are class III histone deacetylase (HDAC) enzymes that target both histone and non-histone substrates. They are linked to different brain functions and the regulation of different isoforms of these enzymes is touted to be an emerging therapy for the treatment of neurodegenerative diseases (NDs), including Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). The level of sirtuins affects brain health as many sirtuin-regulated pathways are responsible for the progression of NDs. Certain sirtuins are also implicated in aging, which is a risk factor for many NDs. In addition to SIRT1-3, it has been suggested that the less studied sirtuins (SIRT4-7) also play critical roles in brain health. This review delineates the role of each sirtuin isoform in NDs from a disease centric perspective and provides an up-to-date overview of sirtuin modulators and their potential use as therapeutics in these diseases. Furthermore, the future perspectives for sirtuin modulator development and their therapeutic application in neurodegeneration are outlined in detail, hence providing a research direction for future studies.
    Matched MeSH terms: Parkinson Disease
  14. Fulltext Challenges and future perspectives for 3D cerebral organoids as amodel for complex brain disorders
    Cheah, Pike-See, Mason, John O., Ling, King-Hwa
    Neuroscience Research Notes, 2019;2(1):1-6.
    MyJurnal
    The human brain is made up of billions of neurons and glial cells which are interconnected and organized into specific patternsof neural circuitry, and hence is arguably the most sophisticated organ in human, both structurally and functionally.Studying the underlying mechanisms responsible for neurologicalor neurodegenerativedisorders and the developmental basis of complex brain diseases such as autism, schizophrenia, bipolar disorder, Alzheimer’s and Parkinson’s disease has proven challenging due to practical and ethical limitations on experiments with human material and the limitationsof existing biological/animal models. Recently,cerebral organoids havebeen proposed as apromisingand revolutionary model for understanding complex brain disorders and preclinical drug screening.
    Matched MeSH terms: Parkinson Disease
  15. LC-MS/MS simultaneous quantification of apomorphine and its major metabolites in human plasma: Application to clinical comparative bioavailability evaluation for the apomorphine sublingual film and a subcutaneous product
    Chen YL, Shi L, Agbo F, Yong SH, Tan PS, Ngounou Wetie AG
    J Pharm Biomed Anal, 2020 Oct 25;190:113493.
    PMID: 32795778 DOI: 10.1016/j.jpba.2020.113493
    A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous quantification of apomorphine and its metabolites apomorphine sulfate and norapomorphine in human plasma for supporting clinical development of a novel apomorphine sublingual thin film (APL) for the treatment of Parkinson's disease. Analytes and internal standards (IS) were extracted from human plasma by Oasis HLB SPE cartridge, followed by a reversed phase LC-MS/MS analysis using multiple reaction monitoring (MRM) in positive mode (m/z 268 → 237 for apomorphine, 348 → 237 for apomorphine sulfate, and 348 → 237 for norapomorphine). Stable isotope-labeled compounds were used as IS for respective analytes. The validated curve ranges were 0.02-20 ng/mL, 10-1000 ng/mL, and 0.5-20 ng/mL for apomorphine, apomorphine sulfate and norapomorphine, respectively. Extraction recoveries were found to be 73.4 % (apomorphine), 81.1 % (apomorphine sulfate), and 58.6 % (norapomorphine). Established long-term plasma frozen storage stabilities were 504 days at -20 °C and276 days at -60 °C, respectively. The method has been successfully used for analyzing pharmacokinetics (PK) samples collected from a comparative bioavailability study of APL and the marketed apomorphine subcutaneous (s.c.) product Apo-go®. The results demonstrated that the 15-mg APL film administrated via sublingual produced comparable PK characteristics of apomorphine when compared to the commercial product Apo-go (2-mg) via s.c. administration, hence establishing the dose regimen for this sublingual formulation. It was also noticed that the sublingual 15-mg APL film produced a significantly higher apomorphine sulfate metabolite level than the 2-mg s.c. Apo-go, and both treatments yielded a negligible level of norapomorphine metabolite in humans.
    Matched MeSH terms: Parkinson Disease
  16. Fulltext Depression In Parkinson Disease: Clinical Features And Aetiology
    Chan, Y.F., Zainal, N.Z.
    Malaysian Journal of Psychiatry, 2010;19(1):1-11.
    MyJurnal
    Parkinson Disease (PD) is a neurodegenerative disorder of the central nervous system that often impairs the patient’s motor skills, speech and other functions. The four cardinal signs of parkinsonism are resting tremor, bradykinesia, cogwheel rigidity and postural instability. The prevalence of depression in PD ranges from 4% to 75%. However depression in PD is often mistakenly as the presentation of the disease itself. Therefore this paper reviewed the clinical feature of depression in PD and explored the aetiology of depression in PD.
    Matched MeSH terms: Parkinson Disease
  17. Fulltext Delayed parkinsonism following high mountain climbing: a case report
    Hur, Tae Hun, Kim, Hyung Jun, Choi, Yun Im, Jeong, Du Shin, Park, Hyung Kook, Yang, Kwang Ik
    Neurology Asia, 2013;18(1):99-101.
    MyJurnal
    Acute mountain sickness is an illness caused by climbing to a high altitude without prior acclimatization. Neurological consequences, like parkinsonism following acute mountain sickness without lesion of brain MRI have been reported rarely. A healthy 56-year-old man presented with dysarthria and gait disturbance. Neurological examination revealed tremor of hands, limb rigidity, and bradykinesia. The symptoms developed approximately 30 days following a 3,500 m climb of the Annapurna in the Himalayas. Brain MRI did not reveal any abnormalities including globus pallidus. The parkinsonism symptoms persisted for about 3 months before a complete recovered was made. We suggest that parkinsonism can develop after climbing to a high altitude but that the symptoms can be transient if a brain MRI detects no abnormalities.
    Matched MeSH terms: Parkinson Disease, Secondary
  18. Fulltext Psychosis in Parkinson's disease patients
    Abdul Hamid Abdul Rahman, Suriati Mohamed Saini, Ibrahim Abu Samah
    ASEAN Journal of Psychiatry, 2013;14(2):96-102.
    MyJurnal
    The objective of this study is to determine the prevalence and factors associated with psychosis in Parkinson’s disease (PD) patients.
    Method: This is a cross-sectional study of 108 PD patients from neurological clinic UKM Medical Centre and Kuala Lumpur Hospital. The patients were recruited from August to December 2004. Psychosis was determined using SCID, the severity of psychosis was rated using BPRS. The cognitive functions were evaluated with MMSE and the severity of depression was assessed with HAM-D.
    Results: The result shows that the prevalence of psychosis in Parkinson's disease patients in this sample was 13%. The psychosis was found to be significantly associated with advancing age, duration of illness, severity of depression and cognitive impairment. Multivariate analysis demonstrates that severity of depression (OR = 1.08, 95% C.I. = 1.01 - 1.16) and advancing age (OR = 4.72, 95% C.I. = 1.37 - 16.29) increased risk of psychosis in PD patients.
    Conclusion: We found that advancing age and severity of depression increase risk to develop psychosis in patients with PD.

    Study site: neurological clinic UKM Medical Centre and Kuala Lumpur Hospita
    Matched MeSH terms: Parkinson Disease
  19. C-Abl Inhibition; A Novel Therapeutic Target for Parkinson's Disease
    Abushouk AI, Negida A, Elshenawy RA, Zein H, Hammad AM, Menshawy A, et al.
    CNS Neurol Disord Drug Targets, 2018 Apr 26;17(1):14-21.
    PMID: 28571531 DOI: 10.2174/1871527316666170602101538
    Parkinson's disease (PD) is the most prevalent movement disorder in the world. The major pathological hallmarks of PD are death of dopaminergic neurons and the formation of Lewy bodies. At the moment, there is no cure for PD; current treatments are symptomatic. Investigators are searching for neuroprotective agents and disease modifying strategies to slow the progress of neurodegeneration. However, due to lack of data about the main pathological sequence of PD, many drug targets failed to provide neuroprotective effects in human trials. Recent evidence suggests the involvement of C-Abelson (c-Abl) tyrosine kinase enzyme in the pathogenesis of PD. Through parkin inactivation, alpha synuclein aggregation, and impaired autophagy of toxic elements. Experimental studies showed that (1) c-Abl activation is involved in neurodegeneration and (2) c-Abl inhibition shows neuroprotective effects and prevents dopaminergic neuronal' death. Current evidence from experimental studies and the first in-human trial shows that c-Abl inhibition holds the promise for neuroprotection against PD and therefore, justifies the movement towards larger clinical trials. In this review article, we discussed the role of c-Abl in PD pathogenesis and the findings of preclinical experiments and the first in-human trial. In addition, based on lessons from the last decade and current preclinical evidence, we provide recommendations for future research in this area.
    Matched MeSH terms: Parkinson Disease
  20. Altered body composition, sarcopenia, frailty, and their clinico-biological correlates, in Parkinson's disease
    Tan AH, Hew YC, Lim SY, Ramli NM, Kamaruzzaman SB, Tan MP, et al.
    Parkinsonism Relat Disord, 2018 11;56:58-64.
    PMID: 29914840 DOI: 10.1016/j.parkreldis.2018.06.020
    INTRODUCTION: Low body weight in Parkinson's disease (PD) is poorly understood despite the associated risks of malnutrition, fractures, and death. Sarcopenia (loss of muscle bulk and strength) and frailty are geriatric syndromes that are likewise associated with adverse health outcomes, yet have received scant attention in PD. We studied body composition, sarcopenia, frailty, and their clinico-biological correlates in PD.

    METHODS: 93 patients and 78 spousal/sibling controls underwent comprehensive assessment of diet, clinical status, muscle strength/performance, frailty, body composition (using dual-energy X-ray absorptiometry), and serum levels of neurogastrointestinal hormones and inflammatory markers.

    RESULTS: PD patients were older than controls (66.0 ± 8.5 vs. 62.4 ± 8.4years, P = 0.003). Mean body mass index (24.0 ± 0.4 vs. 25.6 ± 0.5kg/m2, Padjusted = 0.016), fat mass index (7.4 ± 0.3 vs. 9.0 ± 0.3kg/m2, Padjusted<0.001), and whole-body fat percentage (30.7 ± 0.8 vs. 35.7 ± 0.9%, Padjusted<0.001) were lower in patients, even after controlling for age and gender. There were no between-group differences in skeletal muscle mass index and whole-body bone mineral density. Body composition parameters did not correlate with disease duration or motor severity. Reduced whole-body fat percentage was associated with higher risk of motor response complications as well as higher levels of insulin-growth factor-1 and inflammatory markers. PD patients had a higher prevalence of sarcopenia (17.2% vs. 10.3%, Padjusted = 0.340) and frailty (69.4% vs. 24.2%, Padjusted = 0.010). Older age and worse PD motor severity were predictors of frailty in PD.

    CONCLUSIONS: We found reduced body fat with relatively preserved skeletal muscle mass, and a high prevalence of frailty, in PD. Further studies are needed to understand the patho-mechanisms underlying these alterations.

    Matched MeSH terms: Parkinson Disease
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