Contributing Factors and Evolution of Impulse Control Disorder in the Luxembourg Parkinson Cohort.

Background: To establish the frequency of impulse control disorder (ICD) in Parkinson's disease (PD). Methods: Within the Luxembourg Parkinson's Study, PD patients were evaluated for ICD presence (score ≥ 1 on MDS-UPDRS I item 1.6), use of dopamine agonists (DA) and other medications. Results: 470 patients were enrolled. Among 217 patients without DA use, 6.9% scored positive for ICD, vs. 15.4% among 253 patients with DA use (p = 0.005). The regression analysis showed that age at PD diagnosis had only a minor impact on ICD occurrence, while there was no influence by gender or co-medications. The longitudinal study over 2 years in 156 patients demonstrated increasing ICD frequency in DA users (p = 0.005). Conclusion: This large and non-interventional study confirms that PD patients with DA treatment show higher frequency of ICD than patients without DA use. It newly demonstrates that ICD can develop independently from age, gender, or co-medications

Understanding visual hallucinations: a new synthesis.

Despite decades of research, we do not definitively know how people sometimes see things that are not there. Eight models of complex visual hallucinations have been published since 2000, including Deafferentation, Reality Monitoring, Perception and Attention Deficit, Activation, Input, and Modulation, Hodological, Attentional Networks, Active inference, and Thalamocortical Dysrhythmia Default Mode Network Decoupling. Each was derived from different understandings of brain organisation. To reduce this variability, representatives from each research group agreed an integrated Visual Hallucination Framework that is consistent with current theories of veridical and hallucinatory vision. The Framework delineates cognitive systems relevant to hallucinations. It allows a systematic, consistent, investigation of relationships between the phenomenology of visual hallucinations and changes in underpinning cognitive structures. The episodic nature of hallucinations highlights separate factors associated with the onset, persistence, and end of specific hallucinations suggesting a complex relationship between state and trait markers of hallucination risk. In addition to a harmonised interpretation of existing evidence, the Framework highlights new avenues of research, and potentially, new approaches to treating distressing hallucinations

PENGARUH TEKANAN KETAATAN DAN KOMPLEKSITAS TUGAS TERHADAP AUDIT JUDGMENT (Survey Terhadap Lima Kantor AkuntanPublik di Kota Bandung)

ABSTRAK Seperti yang kita ketahui bahwa seorang auditor dalam melakukan tugasnya membuat audit judgment dipengaruhi banyak faktor, baik bersifat teknis dan non teknis. Salah satu faktor non teknis adalah aspek perilaku individual. Aspek perilaku individu, sebagai salah satu faktor yang banyak mempengaruhi pembuatan audit judgment. Pada penelitian ini ada beberapa faktor yang mempengaruhi audit judgment yaitu tekanan ketaatan dan kompleksitas tugas. Dalam penelitian ini penullis ingin mengetahui sejauh mana “tekanan ketaatan dan kompleksitas tugas terhadap audit judgment”. Sedangkan tujuan dari penelitian ini adalah untuk mengetahui dan mempelajari tekanan ketaatan dan kompleksitas tugas terhadap audit judgment. Hipotesis yang diuji dalam penelitian ini adalah “ jika tekanan ketaatan dan kompleksitas tugas baik, maka audit judgment akan meningkat ( baik pula)”. Hipotesis ini berdasarkan asumsi bahwa tekanan ketaatan dan kompleksitas tugas berpengaruh terhadap audit judgment.dalam penelitian ini penulis menggunakan metode deskriptif asosiatif dengan pendekatan survey dan tes statistik. Penelitian ini terdiri dari atas variabel X1 dan X2 dan audit judgment sebagai veriabel Y atau variabel independen. Uji statistik dilakukan dengan mengolah data dari hasil jawaban kuesioner. Dalam penelitian ini, peulis menyebarkan angket kepada 5 Kantor Akuntan Publik di Kota Bandung khusunya untuk para auditor. Pengumpulan data dilakukan dengan cara penyebaran kuesioner yang telah diuji validitasnya dan reabilitasnya. Penelitian ini dilakukan di 5 KAP di Kota Bandung. Pengambilan sampel ini menggunakan purposive sampling berukuran 28 orang responden. Untuk uji hipotesis penelitian, penulis melakukannya dengan uji t untuk masing-masing variabel X1,X2, dan Y. Dari hasil uji tHitung tekanan ketaatan terhadap audit judgment tHitung =4,178>ttabel = 1.705 kompleksitas tugas terhadap audit judgment 5 tHitung = 3.364 > ttabel = 1,705. Maka, dari hasil uji hipotesis tersebut penulis menyimpulkan bahwa hipotesis penelitian diterima (Ho ditolak, Ha diterima) artinya terdapat pengaruh antara terkanan ketaatan terhadap audit judgment dan kompleksitas tugas terhadap audit judgment Untuk mencari besarnya pengaruh Tekanan ketaatan dan Kompleksitas Tugas terhadap Audit Judgment secara simultan penulis melakukannya dengan uji f dengan koefisien determinasi (KD). Dari hasil uji fhitung dan > f table yaitu 16,182>3,370. Kata kunci : Tekanan Ketaatan dan Kompleksitas tugas Terhadap Audit Judgmen

Mitochondria interaction networks show altered topological patterns in Parkinson's disease.

Mitochondrial dysfunction is linked to pathogenesis of Parkinson's disease (PD). However, individual mitochondria-based analyses do not show a uniform feature in PD patients. Since mitochondria interact with each other, we hypothesize that PD-related features might exist in topological patterns of mitochondria interaction networks (MINs). Here we show that MINs formed nonclassical scale-free supernetworks in colonic ganglia both from healthy controls and PD patients; however, altered network topological patterns were observed in PD patients. These patterns were highly correlated with PD clinical scores and a machine-learning approach based on the MIN features alone accurately distinguished between patients and controls with an area-under-curve value of 0.989. The MINs of midbrain dopaminergic neurons (mDANs) derived from several genetic PD patients also displayed specific changes. CRISPR/CAS9-based genome correction of alpha-synuclein point mutations reversed the changes in MINs of mDANs. Our organelle-interaction network analysis opens another critical dimension for a deeper characterization of various complex diseases with mitochondrial dysregulation

Biomarkers of conversion to alpha-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder

Patients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving \u3b1-synuclein pathology, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal \u3b1-synuclein deposition occurs early in the neurodegenerative process across the central and peripheral nervous systems and might precede the appearance of motor symptoms and cognitive decline by several decades. These findings provide the rationale to develop reliable biomarkers that can better predict conversion to clinically manifest \u3b1-synucleinopathies. In addition, biomarkers of disease progression will be essential to monitor treatment response once disease-modifying therapies become available, and biomarkers of disease subtype will be essential to enable prediction of which subtype of \u3b1-synucleinopathy patients with isolated RBD might develop

The epidemiology of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) in community-living seniors: protocol of the MemoVie cohort study, Luxembourg

BACKGROUND: Cognitive impairment and Alzheimer’s disease (AD) are increasingly considered a major public health problem. The MemoVie cohort study aims to investigate the living conditions or risk factors under which the normal cognitive capacities of the senior population in Luxembourg (≥ 65 year-old) evolve (1) to mild cognitive impairment (MCI) – transitory non-clinical stage – and (2) to AD. Identifying MCI and AD predictors undeniably constitutes a challenge in public health in that it would allow interventions which could protect or delay the occurrence of cognitive disorders in elderly people. In addition, the MemoVie study sets out to generate hitherto unavailable data, and a comprehensive view of the elderly population in the country. METHODS/DESIGN: The study has been designed with a view to highlighting the prevalence in Luxembourg of MCI and AD in the first step of the survey, conducted among participants selected from a random sample of the general population. A prospective cohort is consequently set up in the second step, and appropriate follow-up of the non-demented participants allows improving the knowledge of the preclinical stage of MCI. Case-control designs are used for cross-sectional or retrospective comparisons between outcomes and biological or clinical factors. To ensure maximal reliability of the information collected, we decided to opt for structured face to face interviews. Besides health status, medical and family history, demographic and socio-cultural information are explored, as well as education, habitat network, social behavior, leisure and physical activities. As multilingualism is expected to challenge the cognitive alterations associated with pathological ageing, it is additionally investigated. Data relative to motor function, including balance, walk, limits of stability, history of falls and accidents are further detailed. Finally, biological examinations, including ApoE genetic polymorphism are carried out. In addition to standard blood parameters, the lipid status of the participants is subsequently determined from the fatty acid profiles in their red blood cells. The study obtained the legal and ethical authorizations. DISCUSSION: By means of the multidisciplinary MemoVie study, new insights into the onset of cognitive impairment during aging should be put forward, much to the benefit of intervention strategies as a whole

The Luxembourg Parkinson’s Study: A Comprehensive Approach for Stratification and Early Diagnosis

While genetic advances have successfully defined part of the complexity in Parkinson’s disease (PD), the clinical characterization of phenotypes remains challenging. Therapeutic trials and cohort studies typically include patients with earlier disease stages and exclude comorbidities, thus ignoring a substantial part of the real-world PD population. To account for these limitations, we implemented the Luxembourg PD study as a comprehensive clinical, molecular and device-based approach including patients with typical PD and atypical parkinsonism, irrespective of their disease stage, age, comorbidities, or linguistic background. To provide a large, longitudinally followed, and deeply phenotyped set of patients and controls for clinical and fundamental research on PD, we implemented an open-source digital platform that can be harmonized with international PD cohort studies. Our interests also reflect Luxembourg-specific areas of PD research, including vision, gait, and cognition. This effort is flanked by comprehensive biosampling efforts assuring high quality and sustained availability of body liquids and tissue biopsies. We provide evidence for the feasibility of such a cohort program with deep phenotyping and high quality biosampling on parkinsonism in an environment with structural specificities and alert the international research community to our willingness to collaborate with other centers. The combination of advanced clinical phenotyping approaches including device-based assessment will create a comprehensive assessment of the disease and its variants, its interaction with comorbidities and its progression. We envision the Luxembourg Parkinson’s study as an important research platform for defining early diagnosis and progression markers that translate into stratified treatment approaches

Parkinson’s disease mouse models in translational research

Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson’s disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the validity, strengths, and limitations of current PD mouse models for translational research

Sleep disorders in Parkinson's disease: many causes, few therapeutic options

Sleep symptoms in Parkinson's disease (PD) are frequent and have multifactorial and multilayered causes. Primary involvement of sleep/wake regulating centers in the brainstem, sleep problems caused by the nocturnal manifestation of motor and dysautonomic signs and medication-induced sleep problems are often impossible to disentangle in the individual patient. Two syndromes, hypersomnia and REM sleep behavior disorder (RBD), are increasingly recognized as harbingers of the core PD motor syndrome. RBD, associated with a panoply of other nonmotor symptoms, may predispose to a specific PD phenotype. Long-acting dopaminergic stimulation, when abating nocturnal akinesia, also improves subjective sleep quantity. While this strategy is backed up by several randomized controlled trials (RCT), other treatment recommendations are mostly based on case series or expert opinion. Thus we identified only two other RCT, one treating insomnia with eszopiclone, the other nocturnal behavioral abnormalities in demented PD patients with memantine. While the causal complexity of sleep problems in PD certainly hampers the design of therapeutic studies, multiple general treatment strategies against sleep disorders can however be applied efficiently in PD patients as well