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

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.

Machine learning for predicting neurodegenerative diseases in the general older population: a cohort study.

BACKGROUND: In the older general population, neurodegenerative diseases (NDs) are associated with increased disability, decreased physical and cognitive function. Detecting risk factors can help implement prevention measures. Using deep neural networks (DNNs), a machine-learning algorithm could be an alternative to Cox regression in tabular datasets with many predictive features. We aimed to compare the performance of different types of DNNs with regularized Cox proportional hazards models to predict NDs in the older general population. METHODS: We performed a longitudinal analysis with participants of the English Longitudinal Study of Ageing. We included men and women with no NDs at baseline, aged 60 years and older, assessed every 2 years from 2004 to 2005 (wave2) to 2016-2017 (wave 8). The features were a set of 91 epidemiological and clinical baseline variables. The outcome was new events of Parkinson's, Alzheimer or dementia. After applying multiple imputations, we trained three DNN algorithms: Feedforward, TabTransformer, and Dense Convolutional (Densenet). In addition, we trained two algorithms based on Cox models: Elastic Net regularization (CoxEn) and selected features (CoxSf). RESULTS: 5433 participants were included in wave 2. During follow-up, 12.7% participants developed NDs. Although the five models predicted NDs events, the discriminative ability was superior using TabTransformer (Uno's C-statistic (coefficient (95% confidence intervals)) 0.757 (0.702, 0.805). TabTransformer showed superior time-dependent balanced accuracy (0.834 (0.779, 0.889)) and specificity (0.855 (0.0.773, 0.909)) than the other models. With the CoxSf (hazard ratio (95% confidence intervals)), age (10.0 (6.9, 14.7)), poor hearing (1.3 (1.1, 1.5)) and weight loss 1.3 (1.1, 1.6)) were associated with a higher DNN risk. In contrast, executive function (0.3 (0.2, 0.6)), memory (0, 0, 0.1)), increased gait speed (0.2, (0.1, 0.4)), vigorous physical activity (0.7, 0.6, 0.9)) and higher BMI (0.4 (0.2, 0.8)) were associated with a lower DNN risk. CONCLUSION: TabTransformer is promising for prediction of NDs with heterogeneous tabular datasets with numerous features. Moreover, it can handle censored data. However, Cox models perform well and are easier to interpret than DNNs. Therefore, they are still a good choice for NDs.

Long COVID cognitive sequelae 6 months postinfection and beyond: a scoping review protocol.

INTRODUCTION: The novel and expanding field of long COVID research has undergone diverse methodological approaches in recent years. This protocol lays out the methodological approach, which aims at identifying nuances in current research. It underscores the necessity for a more precise understanding of prolonged cognitive sequelae and their relation to initial disease severity. The findings will add valuable insights for the development of targeted rehabilitation, healthcare interventions and thereby aid patients, clinicians, policymakers and researchers. Our upcoming research is introduced here. METHODS AND ANALYSIS: To map current research in the field, a scoping review will be conducted and documented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Review Extension standards. A systematic search of scientific databases (PubMed, EMBASE), presented 1409 eligible results, published up to 21 December 2023. After removal of duplicates, 925 articles were extracted for screening. Two independent reviewers will screen for titles, abstracts and full texts, to extract data, which will then be organised using charting software. Data for various variables, that is, journal info, studied population demographics, study design, long COVID related data, cognitive outcomes and neuropsychological tests will be gathered. Descriptive analyses, evidence gap maps, heat map quantifications and narrative synthesis will be conducted for reporting of results.This scoping review has been registered with the Open Science Framework (https://doi.org/10.17605/OSF.IO/JHFX6). ETHICS AND DISSEMINATION: Ethical approval is not required, as the study does not involve human participants. The findings will be disseminated through a publication in a scientific journal and within the professional network.

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

Background: Deep 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. Objective: To profile the baseline dataset and to explore risk factors, comorbidities and clinical profiles associated with PD, atypical parkinsonism and controls. Methods: Epidemiological 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. Results: The mean (SD) age at onset (AAO) of PD was 62.3 (11.8) years with 15% early onset (AAO < 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 > 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). Conclusion: Luxembourg 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.

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.

Prevalence and Cost of Care for Parkinson's Disease in Luxembourg: An Analysis of National Healthcare Insurance Data.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder, with an increasing prevalence worldwide. Estimates of the economic burden associated with PD vary widely across existing studies due to differences in setting and study design. The prevalence and cost of care for PD in Luxembourg are currently unknown. OBJECTIVE: The aims of this study were to estimate (1) the prevalence of PD in Luxembourg and (2) the cost of care for PD to the national healthcare insurance based on routinely collected healthcare data. METHODS: This analysis was based on individual patient-level data collected by the national healthcare insurance in Luxembourg during 2007-2017, which covers over 95% of the resident population. People with PD were identified based on drug reimbursement profiles. Cost of care was estimated according to a comparative analysis of the healthcare resources consumed by people with PD compared with an age- and sex-matched control group. RESULTS: We determined a PD prevalence of 928 per 100,000 individuals aged 50 years and older in 2016, higher in men (1032 per 100,000) than in women (831 per 100,000). The total mean cost of care for PD was estimated at €22,673 per patient per year in 2016, with the highest costs being associated with long-term care (69%). CONCLUSION: This was the first attempt to estimate the prevalence and cost of care of PD in Luxembourg. The work demonstrated the usefulness of routinely collected data in Luxembourg for such analyses. Our study confirms the significant burden of PD to the healthcare system, especially on long-term care.

An individualized functional magnetic resonance imaging protocol to assess semantic congruency effects on episodic memory in an aging multilingual population.

The cognitive stimulation induced by multilingualism may slow down age-related memory impairment. However, a suitable neuroscientific framework to assess the influence of multilingualism on age-related memory processes is missing. We propose an experimental paradigm that assesses the effects of semantic congruency on episodic memory using functional magnetic resonance imaging (fMRI). To this end, we modified the picture-word interference (PWI) task to be suitable for the assessment of older multilingual subjects undergoing fMRI. In particular, stimulus materials were prepared in multiple languages (French, German, Luxembourgish, English) and closely matched in semantic properties, thus enabling participants to perform the experiment in a language of their choice. This paradigm was validated in a group (n = 62) of healthy, older participants (over 64 years) who were multilingual, all practicing three or more languages. Consistent with the engagement of semantic congruency processes, we found that the encoding and recognition of semantically related vs. unrelated picture-word pairs evoked robust differences in behavior and the neural activity of parietal-temporal networks. These effects were negligibly modulated by the language used to perform the task. Based on this validation in a multilingual population, we conclude that the proposed paradigm will allow future studies to evaluate whether multilingualism aptitude engages neural systems in a manner that protects long-term memory from aging-related decline.

Depression burden in luxembourg: Individual risk factors, geographic variations and the role of migration, 2013-2015 European Health Examination Survey.

BACKGROUND: Depression is a complex mental disorder that affects an increasing proportion of the worldwide population. This study aims to estimate the prevalence of depressive symptoms in Luxembourg, associated risk factors and geographic variations. Additionally, it aims to assess whether first and second generation immigrants are at higher risk for depressive symptoms compared to non-immigrants. METHODS: Representative cross-sectional data from 1499 residents of Luxembourg, aged 25-64 years, were collected from the Luxembourg European Health Survey (EHES-LUX). Depressive symptoms were defined as a score of ≥5 on the Patient Health Questionnaire for depression (PHQ-9) (i.e. mild, moderate or severe). Standard and Bayesian regression models were used to examine associations between depressive symptoms, immigration status and geographic distribution across Luxembourg. RESULTS: The prevalence of depressive symptoms was 21.55% (15.54% mild, 3.54% moderate, and 2.49% moderately severe to severe). The odds of having depressive symptoms was higher among second generation immigrants compared to non-immigrants (OR: 1.58, 95% CI: 1.04, 2.41), independent of socioeconomic and behavioral characteristics. Healthier diet, higher social support and good health perception were protective towards experiencing depressive symptoms. One of the highest likelihoods of reporting depressive symptoms was observed in the South-West of the country with a positive effect at 80% credible region [CR] (1.42 [0.92, 2.73]). LIMITATIONS: The participation rate was low (26.7%). The cross-sectional nature of the study does not allow us to establish causality. CONCLUSIONS: Depression constitutes an important public health challenge in Luxembourg due to the impact on the overall health of the population. Social programs of health promotion should be developed to improve mental wellbeing in immigrants, especially those of second generation.

Prevalence of Dementia and Cognitive Complaints in the Context of High Cognitive Reserve: A Population-Based Study.

OBJECTIVES: This study aimed to assess the prevalence of dementia and cognitive complaints in a cross-sectional sample of Luxembourg seniors, and to discuss the results in the societal context of high cognitive reserve resulting from multilingualism. METHODS: A population sample of 1,377 people representative of Luxembourg residents aged over 64 years was initially identified via the national social insurance register. There were three different levels of contribution: full participation in the study, partial participation, and non-participation. We examined the profiles of these three different samples so that we could infer the prevalence estimates in the Luxembourgish senior population as a whole using the prevalence estimates obtained in this study. RESULTS: After careful attention to the potential bias and of the possibility of underestimation, we considered the obtained prevalence estimates of 3.8% for dementia (with corresponding 95% confidence limits (CL) of 2.8% and 4.8%) and 26.1% for cognitive complaints (CL = [17.8-34.3]) as trustworthy. CONCLUSION: Based on these findings, we postulate that high cognitive reserve may result in surprisingly low prevalence estimates of cognitive complaints and dementia in adults over the age of 64 years, which thereby corroborates the longer disability-free life expectancy observed in the Luxembourg population. To the best of our knowledge, this study is the first to report such Luxembourgish public health data.

Lifelong exposure to multilingualism: new evidence to support cognitive reserve hypothesis.

OBJECTIVE: Investigate the protective effect of multilingualism on cognition in seniors. METHODS: As part of the MemoVie study conducted on 232 non-demented volunteers aged 65 and more, neurogeriatric and neuropsychological evaluations were performed. Participants were classified as presenting either cognitive impairment without dementia (CIND) or being free of any cognitive impairment (CIND-free). Language practices, socio-demographic data and lifestyle habits were recorded. In this retrospective nested case-control design, we used as proxies of multilingualism: number of languages practiced, age of acquisition and duration of practice, emphasizing the temporal pattern of acquisition, and the resulting practice of several languages sequentially or concomitantly during various periods of life. This special angle on the matter offered to our work a dimension particularly original and innovative. RESULTS: 44 subjects (19%) had CIND, the others were cognitively normal. All practiced from 2 to 7 languages. When compared with bilinguals, participants who practiced more than 2 languages presented a lower risk of CIND, after adjustment for education and age (odds ratio (OR) = 0.30, 95% confidence limits (95%CL) = [0.10-0.92]). Progressing from 2 to 3 languages, instead of staying bilingual, was associated with a 7-fold protection against CIND (OR = 0.14, 95%CL = [0.04-0.45], p = 0.0010). A one year delay to reach multilingualism (3 languages practiced being the threshold) multiplied the risk of CIND by 1.022 (OR = 1.022, 95%CL = [1.01-1.04], p = 0.0044). Also noteworthy, just as for multilingualism, an impact of cognitively stimulating activities on the occurrence of CIND was found as well (OR = 0.979, 95%CL = [0.961-0.998], p = 0.033). CONCLUSION: The study did not show independence of multilingualism and CIND. Rather it seems to show a strong association toward a protection against CIND. Practicing multilingualism from early life on, and/or learning it at a fast pace is even more efficient. This protection might be related to the enhancement of cognitive reserve and brain plasticity, thereby preserving brain functions from alterations during aging.