Mixed effects models but not t-tests or linear regression detect progression of apathy in Parkinson’s disease over seven years in a cohort: a comparative analysis

peer reviewedIntroduction While there is an interest in defining longitudinal change in people with chronic illness like Parkinson’s disease (PD), statistical analysis of longitudinal data is not straightforward for clinical researchers. Here, we aim to demonstrate how the choice of statistical method may influence research outcomes, (e.g., progression in apathy), specifically the size of longitudinal effect estimates, in a cohort. Methods In this retrospective longitudinal analysis of 802 people with typical Parkinson’s disease in the Luxembourg Parkinson's study, we compared the mean apathy scores at visit 1 and visit 8 by means of the paired two-sided t-test. Additionally, we analysed the relationship between the visit numbers and the apathy score using linear regression and longitudinal two-level mixed effects models. Results Mixed effects models were the only method able to detect progression of apathy over time. While the effects estimated for the group comparison and the linear regression were smaller with high p-values (+ 1.016/ 7 years, p = 0.107, -0.056/ 7 years, p = 0.897, respectively), effect estimates for the mixed effects models were positive with a very small p-value, indicating a significant increase in apathy symptoms by + 2.345/ 7 years (p < 0.001). Conclusion The inappropriate use of paired t-tests and linear regression to analyse longitudinal data can lead to underpowered analyses and an underestimation of longitudinal change. While mixed effects models are not without limitations and need to be altered to model the time sequence between the exposure and the outcome, they are worth considering for longitudinal data analyses. In case this is not possible, limitations of the analytical approach need to be discussed and taken into account in the interpretation

Determinants of Self-Stigma in People with Parkinson's Disease: A Mixed Methods Scoping Review

Background: Self-stigma in people with Parkinson's disease (PD) can substantially impact quality of life and possibilities for social participation. An integrative analysis of determinants of self-stigma has been lacking. Objective: We sought to explore which complementary insights from qualitative and quantitative studies, as well as from expert consultation, could be gained. Methods: An established mixed methods study design was employed to first conduct a mixed methods scoping review of published qualitative and quantitative literature, and then consult with experts to arrive at an exhaustive list of determinants of self-stigma after a thematic synthesis. Results: A total of 87 unique determinants of self-stigma were identified. Quantitative studies and expert consultations mainly identified personal determinants of people with self-stigma (e.g., age, anxiety, or apathy). In contrast, qualitative studies identified social situations associated with self-stigma (e.g., joint meals of people with typical PD with others). Notably, self-stigma of people with PD was found to be particularly salient in unfamiliar places, at the working place or in contact with people without PD. Across methods, cognitive impairment, tremor, and abnormal walk and unsteady gait, respectively, were associated with self-stigma. Conclusion: The mixed method study design yielded complementary insights, but also factors commonly associated with self-stigma across methods. Future prioritization exercises may gain further insights into self-stigma of people with PD. Facilitating social encounters by both addressing needs of affected people and raising knowledge and public awareness may improve quality of life in people with P

Validation of a Parkinson's disease questionnaire-39-based functional mobility composite score (FMCS) in people with Parkinson's disease.

INTRODUCTION: Functional mobility is an important outcome for people with Parkinson's disease (PwP). Despite this, there is no established patient-reported outcome measure that serves as a gold standard for assessing patient-reported functional mobility in PwP. We aimed to validate the algorithm calculating the Parkinson's Disease Questionnaire-39 (PDQ-39) based Functional Mobility Composite Score (FMCS). METHODS: We designed a count-based algorithm to measure patient-reported functional mobility in PwP from items of the PDQ-39 subscales mobility and activities of daily living. Convergent validity of the algorithm calculating the PDQ-39-based FMCS was assessed using the objective Timed Up and Go (n = 253) and discriminative validity was assessed by comparing the FMCS with patient-reported (MDS-UPDRS II) and clinician-assessed (MDS-UPDRS III) motor symptoms as well as between disease stages (H&Y) and PIGD phenotypes (n = 736). Participants were between 22 and 92 years old, with a disease duration from 0 to 32 years and 64.9% in a H&Y 1-2 ranging from 1 to 5. RESULTS: Spearman correlation coefficients (r(s)) ranging from -0.45 to -0.77 (p < 0.001) indicated convergent validity. Hence, a t-test suggested sufficient ability of the FMCS to discriminate (p < 0.001) between patient-reported and clinician-assessed motor symptoms. More specifically, FMCS was more strongly associated with patient-reported MDS-UPDRS II (r(s) = -0.77) than clinician-reported MDS-UPDRS III (r(s) = -0.45) and can discriminate between disease stages as between PIGD phenotypes (p < 0.001). CONCLUSION: The FMCS is a valid composite score to assess functional mobility through patient reports in PwP for studying functional mobility in studies using the PDQ-39

Sex-specific progression of Parkinson’s disease: A longitudinal mixed-models analysis

BACKGROUND: Despite its relevance, the clinical progression of motor- and non-motor symptoms associated with Parkinson’s disease (PD) is poorly described and understood, particularly in relation to sex-specific differences in clinical progression.OBJECTIVES: Identification of differential aspects in disease progression in men and women with PD.METHODS: Linear mixed-model analyses of a total of 802 people with typical PD from the Luxembourg Parkinson’s study’s prospective cohort, stratified by sex. Marginal effects of disease duration on the outcomes (disease duration averaged over random effects) in analyses stratified by sex were estimated and illustrated for the following outcomes: MDS-UPDRS I-IV, apathy, depression, global cognition, olfaction, bodily discomfort, rapid eye movement sleep behaviour disorder, quality of sleep, dysphagia, patient-reported functional mobility, postural instability and gait disturbances and tremor. Men and women had similar age and median time of follow-up was 3 years.RESULTS: Compared to men, we observed slower disease progression in women for cognition, apathy, quality of sleep and MDS-UPDRS II and significantly worse scores for depression and pain at baseline. Only bodily discomfort and depression (in the first ten years since diagnosis) progressed faster in women. Intensity of tremor decreased over time for both groups.CONCLUSION: Differential progression of symptoms in men and women with PD exists and needs to be explored further. To enhance well-being in PD, we recommend considering a sex-specific approach to managing PD symptoms.</p

Determinants of patient-reported functional mobility in people with Parkinson's disease: A systematic review.

peer reviewed[en] BACKGROUND: Information on determinants of patient-reported functional mobility is lacking but would inform the planning of healthcare, resources and strategies to promote functional mobility in people with Parkinson's disease (PD). RESEARCH QUESTION: To identify the determinants of patient-reported functional mobility of people with PD. METHODS: Eligible: Randomized Controlled Trials, cohort, case-control, or cross-sectional analyses in people PD without date or setting restrictions, published in English, German, or French. Excluded: instruments with under 50 % of items measuring mobility. On August 9th 2023 we last searched Medline, CINAHL and PsychInfo. We assessed risk of bias using the mixed-methods appraisal tool. Results were synthesized by tabulating the determinants by outcomes and study designs. RESULTS: Eleven studies published 2012-2023 were included (most in Swedish outpatient settings). Samples ranged from 9 to 255 participants. Follow-up varied from 1.5 to 36 months with attrition of 15-42 %. Heterogenic study designs complicated results synthesis. However, determinants related to environment seem to associate the strongest with patient-reported functional mobility, although determinants related to body structures and functions were most investigated. We identified disease duration, the ability to drive, caregiving, sex, age, cognitive impairment, postural instability and social participation as determinants of patient-reported functional mobility. DISCUSSION: Methodological quality of the studies was limited. No study reported an a priori power calculation. Three studies controlled for confounders. The included studies lack representativeness of the population of people living with PD. Standardized sets of outcomes could enable more systematic research synthesis. CONCLUSIONS: Future research should focus on activities, participation and environmental factors and improve methodological quality

Impact of COVID-19 Pandemic on (Health) Care Situation of People with Parkinson’s Disease in Germany (Care4PD)

The Care4PD study examined the impact of the COVID-19 pandemic on the care situation of people (PwP) with Parkinson’s disease in Germany. A comprehensive, nationwide, anonymous questionnaire for PwP was distributed by the members’ journal of the German Parkinson’s Disease Association and in several PD specialized in- and outpatient institutions. PwP subjectively evaluated their general care situation and individual impairments during the pandemic. We analyzed 1269 eligible out of 1437 returned questionnaires (88.3%) and compared PwP with (p-LTC) and without (np-LTC) professional long-term care. Both groups rated the general pandemic-related consequences as being rather mild to moderate (e.g., worsening of symptom or concerns). However, familial/social contact restrictions were indicated as most compromising, whereas access to outpatient professional health care providers was less affected. PwP with professional LTC reported more impairment than those without. COVID-19 vaccination rates and acceptance were generally high (p-LTC: 64.3%, np-LTC: 52.3%) at the time of the study, but realization of sanitary measures—especially wearing masks as a patient during care sessions—still needs to be improved. Technical options for telemedicine were principally available but only rarely used. Altogether, during the COVID-19 pandemic, PwP in Germany seemed to have a relatively stable health care access, at least in outpatient settings, while mainly social isolation compromised them. The p-LTC group was more impaired in everyday live compared with the np-LTC group

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

Luxembourg Parkinson’s study -comprehensive baseline analysis of Parkinson’s disease and atypical parkinsonism

BackgroundDeep phenotyping of Parkinson’s disease (PD) is essential to investigate this fastest-growing neurodegenerative disorder. Since 2015, over 800 individuals with PD and atypical parkinsonism along with more than 800 control subjects have been recruited in the frame of the observational, monocentric, nation-wide, longitudinal-prospective Luxembourg Parkinson’s study.ObjectiveTo profile the baseline dataset and to explore risk factors, comorbidities and clinical profiles associated with PD, atypical parkinsonism and controls.MethodsEpidemiological and clinical characteristics of all 1,648 participants divided in disease and control groups were investigated. Then, a cross-sectional group comparison was performed between the three largest groups: PD, progressive supranuclear palsy (PSP) and controls. Subsequently, multiple linear and logistic regression models were fitted adjusting for confounders.ResultsThe mean (SD) age at onset (AAO) of PD was 62.3 (11.8) years with 15% early onset (AAO &lt; 50 years), mean disease duration 4.90 (5.16) years, male sex 66.5% and mean MDS-UPDRS III 35.2 (16.3). For PSP, the respective values were: 67.6 (8.2) years, all PSP with AAO &gt; 50 years, 2.80 (2.62) years, 62.7% and 53.3 (19.5). The highest frequency of hyposmia was detected in PD followed by PSP and controls (72.9%; 53.2%; 14.7%), challenging the use of hyposmia as discriminating feature in PD vs. PSP. Alcohol abstinence was significantly higher in PD than controls (17.6 vs. 12.9%, p = 0.003).ConclusionLuxembourg Parkinson’s study constitutes a valuable resource to strengthen the understanding of complex traits in the aforementioned neurodegenerative disorders. It corroborated several previously observed clinical profiles, and provided insight on frequency of hyposmia in PSP and dietary habits, such as alcohol abstinence in PD.Clinical trial registration: clinicaltrials.gov, NCT05266872

Subjective Cognitive Complaints in Participants of the Healthy Brain Ageing Study (HeBA)

Subjective cognitive complaints (SCC) have the potential for earlier detection of Alzheimer’s disease and Parkinson’s disease. Currently, the results of the completed online survey in the frame of the HeBA study reveal that 23% of the Luxembourgish participants have SCC with the SCC group having a higher prevalence rate of depression

Creation of a pandemic memory by tracing COVID-19 infections and immunity in Luxembourg (CON-VINCE).

peer reviewed[en] BACKGROUND: During the COVID-19 pandemic swift implementation of research cohorts was key. While many studies focused exclusively on infected individuals, population based cohorts are essential for the follow-up of SARS-CoV-2 impact on public health. Here we present the CON-VINCE cohort, estimate the point and period prevalence of the SARS-CoV-2 infection, reflect on the spread within the Luxembourgish population, examine immune responses to SARS-CoV-2 infection and vaccination, and ascertain the impact of the pandemic on population psychological wellbeing at a nationwide level. METHODS: A representative sample of the adult Luxembourgish population was enrolled. The cohort was followed-up for twelve months. SARS-CoV-2 RT-qPCR and serology were conducted at each sampling visit. The surveys included detailed epidemiological, clinical, socio-economic, and psychological data. RESULTS: One thousand eight hundred sixty-five individuals were followed over seven visits (April 2020-June 2021) with the final weighted period prevalence of SARS-CoV-2 infection of 15%. The participants had similar risks of being infected regardless of their gender, age, employment status and education level. Vaccination increased the chances of IgG-S positivity in infected individuals. Depression, anxiety, loneliness and stress levels increased at a point of study when there were strict containment measures, returning to baseline afterwards. CONCLUSION: The data collected in CON-VINCE study allowed obtaining insights into the infection spread in Luxembourg, immunity build-up and the impact of the pandemic on psychological wellbeing of the population. Moreover, the study holds great translational potential, as samples stored at the biobank, together with self-reported questionnaire information, can be exploited in further research. TRIAL REGISTRATION: Trial registration number: NCT04379297, 10 April 2020.3. Good health and well-bein