References of "Krüger, Rejko 50002143"
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See detailDairy Intake and Parkinson's Disease: A Mendelian Randomization Study
Domenighetti, Cloé; Sugier, Pierre-Emmanuel; Ashok Kumar Sreelatha, Ashwin et al

in Movement Disorders (2022)

Abstract Background Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained ... [more ▼]

Abstract Background Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained by reverse causation or confounding. Objective The aim is to examine the association between genetically predicted dairy intake and PD using two-sample Mendelian randomization (MR). Methods We genotyped a well-established instrumental variable for dairy intake located in the lactase gene (rs4988235) within the Courage-PD consortium (23 studies; 9823 patients and 8376 controls of European ancestry). Results Based on a dominant model, there was an association between genetic predisposition toward higher dairy intake and PD (odds ratio [OR] per one serving per day = 1.70, 95 confidence interval = 1.12–2.60, P = 0.013) that was restricted to men (OR = 2.50 [1.37–4.56], P = 0.003; P-difference with women = 0.029). Conclusions Using MR, our findings provide further support for a causal relationship between dairy intake and higher PD risk, not biased by confounding or reverse causation. Further studies are needed to elucidate the underlying mechanisms. © 2022 International Parkinson and Movement Disorder Society [less ▲]

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See detailWhich demographic and socio-economic factors are associated with vaccination willingness and beliefs towards vaccination? Rapid report with first results
Leist, Anja UL; Klee, Matthias UL; Paccoud, Ivana UL et al

Report (2021)

In the framework of the CoVaLux project on vaccination and long COVID in Luxembourg, the project “Socio-economic determinants of long COVID and vaccination, and economic consequences with focus on labour ... [more ▼]

In the framework of the CoVaLux project on vaccination and long COVID in Luxembourg, the project “Socio-economic determinants of long COVID and vaccination, and economic consequences with focus on labour market and health care” aims to triangulate evidence from different data sources such as social security and general population data, the national cohort CON-VINCE as well as national health surveys. We seek to arrive at robust assessments of how socio-economic determinants shape vaccination willingness, occurrence, severity and persistence of long COVID, and economic consequences of long COVID in Luxembourg. [less ▲]

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See detailGene-corrected p.A30P SNCA patient-derived isogenic neurons rescue neuronal branching and function
Barbuti, Peter A; Ohnmacht, Jochen UL; Santos, Bruno FR et al

in Scientific Reports (2021), 11

Parkinson’s disease (PD) is characterised by the degeneration of A9 dopaminergic neurons and the pathological accumulation of alpha-synuclein. The p.A30P SNCA mutation generates the pathogenic form of the ... [more ▼]

Parkinson’s disease (PD) is characterised by the degeneration of A9 dopaminergic neurons and the pathological accumulation of alpha-synuclein. The p.A30P SNCA mutation generates the pathogenic form of the alpha-synuclein protein causing an autosomal-dominant form of PD. There are limited studies assessing pathogenic SNCA mutations in patient-derived isogenic cell models. Here we provide a functional assessment of dopaminergic neurons derived from a patient harbouring the p.A30P SNCA mutation. Using two clonal gene-corrected isogenic cell lines we identified image-based phenotypes showing impaired neuritic processes. The pathological neurons displayed impaired neuronal activity, reduced mitochondrial respiration, an energy deficit, vulnerability to rotenone, and transcriptional alterations in lipid metabolism. Our data describes for the first time the mutation-only effect of the p.A30P SNCA mutation on neuronal function, supporting the use of isogenic cell lines in identifying image-based pathological phenotypes that can serve as an entry point for future disease-modifying compound screenings and drug discovery strategies. [less ▲]

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See detailTherapeutic maps for a sensor-based evaluation of deep brain stimulation programming
Bremm, René Peter UL; Berthold; Krüger, Rejko UL et al

in Biomedizinische Technik. Biomedical Engineering (2021)

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See detailGenetic evaluation of dementia with Lewy bodies implicates distinct disease subgroups
Kaivola, Karri; Shah, Zalak; Chia, Ruth et al

in Brain: a Journal of Neurology (2021), awab402

The APOE locus is strongly associated with risk for developing Alzheimer’s disease and dementia with Lewy bodies (DLB). In particular, the role of the APOE ε4 allele as a putative driver of α-synuclein ... [more ▼]

The APOE locus is strongly associated with risk for developing Alzheimer’s disease and dementia with Lewy bodies (DLB). In particular, the role of the APOE ε4 allele as a putative driver of α-synuclein pathology is a topic of intense debate. Here, we performed a comprehensive evaluation in 2,466 DLB cases versus 2,928 neurologically healthy, aged controls. Using an APOE-stratified genome-wide association study approach, we found that GBA is associated with risk for DLB in patients without APOE ε4 (p = 6.58 x 10−9, OR = 3.41, 95% CI = 2.25–5.17), but not with DLB with APOE ε4 (p = 0.034, OR = 1.87, 95%, 95% CI = 1.05–3.37). We then divided 495 neuropathologically examined DLB cases into three groups based on the extent of concomitant Alzheimer’s disease co-pathology: pure DLB (n = 88), DLB with intermediate Alzheimer’s disease co-pathology (DLB + iAD, n = 66), and DLB with high Alzheimer’s disease co-pathology (DLB + AD, n = 341). In each group, we tested the association of the APOE ε4 against the 2,928 neurologically healthy controls. Our examination found that APOE ε4 was associated with DLB + AD (p = 1.29x10−32, OR = 4.25, 95% CI = 3.35–5.39) and DLB + iAD (p = 0.0011, OR = 2.31, 95% CI = 1.40–3.83), but not with pure DLB (p = 0.31, OR = 0.75, 95% CI = 0.43–1.30). In conclusion, though deep clinical data were not available for these samples, our findings do not support the notion that APOE ε4 is an independent driver of α-synuclein pathology in pure DLB, but rather implicate GBA as the main risk gene for the pure DLB subgroup. [less ▲]

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See detailMendelian randomization study of smoking, alcohol, and coffee drinking in relation to Parkinso's disease
Domenighetti, Cloe; Sugier, Pierre Emmanuel; Sreelatha, Ashwin Ashok Kumar et al

in Journal of Parkinson's Disease (2021)

Background:Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson’s disease (PD). The prodromal phase of PD raises the possibility ... [more ▼]

Background:Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson’s disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. Objective:To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. Methods:We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used the inverse-variance weighted method to compute odds ratios (ORIVW) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p = 0.017). Results:We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60–0.93, p = 0.009) without significant directional pleiotropy. Associations in participants ≤67 years old and cases with disease duration ≤7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. Conclusion:Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power. [less ▲]

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See detailA new brain organoid model to study Parkinson’s Disease
Bolognin, Silvia UL; Smits, Lisa UL; Nickels, Sarah Louise UL et al

in Biomedical Science and Engineering (2021)

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See detailThe retrograde procedural memory in people with Parkinson’s disease with or without freezing of gait – a cross-sectional study
Pauly, Laure UL; Rauschenberger, Armin UL; Pauly, Claire UL et al

Poster (2021, September 17)

Objective: To investigate the retrograde procedural memory in people with typical Parkinson’s disease (PwP) with or without freezing of gait (FOG). We hypothesized that the retrograde procedural memory is ... [more ▼]

Objective: To investigate the retrograde procedural memory in people with typical Parkinson’s disease (PwP) with or without freezing of gait (FOG). We hypothesized that the retrograde procedural memory is more strongly impaired in patients with FOG (FOG+) than in patients without FOG (FOG-). Background: Given that cognitive functions, like executive control and automaticity, are crucial for mobility, it is of great importance to get a deeper knowledge of the cognitive impairment that may interfere with walking and causing gait disturbances in PwP, i.e. FOG. The integrity of retrograde procedural memory, the ability to execute skills that have been learned in earlier life stages, is essential for a person’s ability to complete routine, procedural activities like walking. As FOG is characterized as a de-automatization disorder, we hypothesized an impairment of the retrograde procedural memory in patients with FOG. Methods: A total of 194 patients from the Luxembourg Parkinson’s study were included into the cross-sectional study. All patients were assigned to the FOG+ / FOG- groups based on a semi-structured interview conducted by a study physician. The extended evaluation system of the cube copying test was applied to evaluate both the cube-drawing procedure, representing the retrograde procedural memory, and the final result, representing the visuo-constructive abilities (Pauly et al., 2020, MDS abstract). We compared the cube copying performance of n=97 FOG+ with n=97 age-, gender- and education-matched FOG-. Results: FOG+ scored lower on the cube copying procedure compared to the FOG- (p=0.027), which is suggestive of an impaired retrograde procedural memory in FOG+. No significant differences in the visuo-constructional abilities were detected (p=0.945). Conclusion: In line with FOG being considered a de-automatization of walking, a skill acquired in earlier life stages, the present results suggest that PwP with FOG have an impaired retrograde procedural memory in comparison to PwP without FOG. The results lend support to the ability of the extended evaluation system of the cube copying test to assess impaired retrograde procedural memory and help improve our understanding of behavioral symptoms in PwP. [less ▲]

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See detailThe evolution and social determinants of mental health during the first wave of the COVID-19 outbreak in Luxembourg
Ribeiro, Fabiana UL; Schröder, Valerie UL; Krüger, Rejko UL et al

in Psychiatry Research (2021), 303

Studies have been showing a negative impact of pandemic control measures on mental health. However, few studies assessed these effects longitudinally during the peak of the first wave of the COVID-19 ... [more ▼]

Studies have been showing a negative impact of pandemic control measures on mental health. However, few studies assessed these effects longitudinally during the peak of the first wave of the COVID-19 pandemic. The goals of this study were to explore whether differential effects of COVID-19 restrictions on mental health could be observed by sex and age in a Luxembourgish nationally representative sample during the initial outbreak of COVID-19. Furthermore, we aimed to assess whether there are differences in risk and protective factors longitudinally at two assessment times. A total of 1,756 respondents aged 18 years and older (50.74% women) reported sociodemographic and socio-economic characteristics, depression, anxiety, stress, and loneliness. Women and younger respondents reported higher rates of severe depression and anxiety symptoms, suggesting higher vulnerability to the pandemic control measures. This study contributes to the investigation of mental health consequences of the pandemic and the pandemic control measures, particularly related to shifts in care task responsibilities, gender and socio-economic inequalities, as well as younger groups' uncertainty about the future. [less ▲]

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See detailReplication of a Novel Parkinson's Locus in a European Ancestry Population
Grover, Sandeep; Kumar-Sreelatha, Ashwin Ashok; Bobbili, Dheeraj R. et al

in Movement Disorders (2021)

ABSTRACT Background A recently published East Asian genome-wide association study of Parkinson;s disease (PD) reported 2 novel risk loci, SV2C and WBSCR17. Objectives The objective of this study were to ... [more ▼]

ABSTRACT Background A recently published East Asian genome-wide association study of Parkinson;s disease (PD) reported 2 novel risk loci, SV2C and WBSCR17. Objectives The objective of this study were to determine whether recently reported novel SV2C and WBSCR17 loci contribute to the risk of developing PD in European and East Asian ancestry populations. Methods We report an association analysis of recently reported variants with PD in the COURAGE-PD cohort (9673 PD patients; 8465 controls) comprising individuals of European and East Asian ancestries. In addition, publicly available summary data (41,386 PD patients; 476,428 controls) were pooled. Results Our findings confirmed the role of the SV2C variant in PD pathogenesis (rs246814, COURAGE-PD PEuropean = 6.64 × 10−4, pooled PD P = 1.15 × 10−11). The WBSCR17 rs9638616 was observed as a significant risk marker in the East Asian pooled population only (P = 1.16 × 10−8). Conclusions Our comprehensive study provides an up-to-date summary of recently detected novel loci in different PD populations and confirmed the role of SV2C locus as a novel risk factor for PD irrespective of the population or ethnic group analyzed. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society [less ▲]

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See detailGenome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture
Chia, Ruth; Sabir, Marya S.; Bandres-Ciga, Sara et al

in Nature Genetics (2021)

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic ... [more ▼]

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer’s disease and Parkinson’s disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition. [less ▲]

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See detailPathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
Dewan, Ramita; Chia, Ruth; Ding, Jinhui et al

in Neuron (2021), 109(3), 448-460

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients ... [more ▼]

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered. [less ▲]

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See detailThe Parkinson’s-disease-associated mutation LRRK2-G2019S alters dopaminergic differentiation dynamics via NR2F1
Walter, Jonas; Bolognin, Silvia UL; Poovathingal, Suresh et al

in Cell Reports (2021)

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See detailEditorial: Celebrating the Diversity of Genetic Research to Dissect the Pathogenesis of Parkinson's Disease
Farrer, Matthew J.; Bardien, Soraya; Hattori, Nobutaka et al

in Frontiers in Neurology (2021), 12

Parkinson's disease (PD) is the fastest growing neurological disorder worldwide, taking into account age-standardized rates for prevalence, disability and deaths (1). PD is characterized by a clinical ... [more ▼]

Parkinson's disease (PD) is the fastest growing neurological disorder worldwide, taking into account age-standardized rates for prevalence, disability and deaths (1). PD is characterized by a clinical symptomatology involving both motor and non-motor symptoms. According to the Global Burden of Disease study (2018), the global burden of this disorder has more than doubled over the past two decades from 2.5 million patients in 1990 to 6.1 million patients in 2016 (2). In this editorial and eBook, we highlight the research done on PD by members of a global consortium known as the Genetic Epidemiology of Parkinson's disease (GEoPD) Consortium. We begin the editorial by providing a brief history of how GEoPD was started and how it has subsequently developed into an international endeavor. We then briefly summarize the completed and ongoing projects, and conclude with the future vision of this unique consortium. [less ▲]

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See detailQuantifying activities of daily living impairment in Parkinson’s disease using the Functional Activities Questionnaire
Becker, Sara; Pauly, Claire UL; Lawton, Michael et al

in Neurological Sciences (2021)

Objective Cognitive-driven activity of daily living (ADL) impairment in Parkinson’s disease (PD) is increasingly discussed as prodromal marker for dementia. Diagnostic properties of assessments for this ... [more ▼]

Objective Cognitive-driven activity of daily living (ADL) impairment in Parkinson’s disease (PD) is increasingly discussed as prodromal marker for dementia. Diagnostic properties of assessments for this specifc ADL impairment are sparsely investigated in PD. The ability of the Functional Activities Questionnaire (FAQ) for diferentiating between PD patients with normal cognition and with mild cognitive impairment (PD-MCI), according to informant and self-reports, was examined. Global cognitive function in groups with and without mild ADL impairment was compared according to diferent cut-ofs. Methods Multicenter data of 589 patients of an international cohort (CENTRE-PD) were analyzed. Analyses were run separately for informant-rated and self-rated FAQ. Receiver operating characteristic (ROC) analysis was conducted to defne the optimal FAQ cut-of for PD-MCI (≥1), and groups were additionally split according to reported FAQ cut-ofs for PD-MCI in the literature (≥3,≥5). Binary logistic regressions examined the efect of the Montreal Cognitive Assessment (MoCA) score in PD patients with and without mild ADL impairment. Results Two hundred and twenty-fve (38.2%) patients were classifed as PD-MCI. For all three cut-of values, sensitivity was moderate to low (<0.55), but specifcity was moderately high (>0.54) with a tendency of higher values for self-reported defcits. For the self-report, the cut-of≥3 showed a signifcant efect of the MoCA (B= −0.31, p=0.003), where FAQ≥3 patients had worse cognition. No efect for group diferences based on informant ratings was detected. Conclusion Our data argue that self-reported ADL impairments assessed by the FAQ show a relation to the severity of cognitive impairment in PD. [less ▲]

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See detailPINK1 deficiency impairs adult neurogenesis of dopaminergic neurons
Brown, Sarah J; Boussaad, Ibrahim UL; Jarazo, Javier UL et al

in Scientific Reports (2021)

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