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

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 < 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).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

Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes

Several phenotypic differences observed in Parkinson’s disease (PD) patients have been linked to age at onset (AAO). We endeavoured to find out whether these differences are due to the ageing process itself by using a combined dataset of idiopathic PD (n = 430) and healthy controls (HC; n = 556) excluding carriers of known PD-linked genetic mutations in both groups. We found several significant effects of AAO on motor and non-motor symptoms in PD, but when comparing the effects of age on these symptoms with HC (using age at assessment, AAA), only positive associations of AAA with burden of motor symptoms and cognitive impairment were significantly different between PD vs HC. Furthermore, we explored a potential effect of polygenic risk score (PRS) on clinical phenotype and identified a significant inverse correlation of AAO and PRS in PD. No significant association between PRS and severity of clinical symptoms was found. We conclude that the observed non-motor phenotypic differences in PD based on AAO are largely driven by the ageing process itself and not by a specific profile of neurodegeneration linked to AAO in the idiopathic PD patients

Etude épidémiologique et moléculaire des voies métaboliques associées au glutathion dans le cancer du sein

NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

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

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

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

<div><p>Objectives</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusion</p><p>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.</p></div

Distribution of data available for the three types of population.

<p>^a: the <i>p</i>-value was derived from Chi-squared test</p><p>^b: the <i>p</i>-value was derived from Kruskal-Wallis test</p><p>Distribution of data available for the three types of population.</p

Answers supplied for “lifestyle.”

<p>(A) Lifestyle distribution depending on population. (B) Representativeness depending on lifestyle: the overall participants compared to the Luxembourgish seniors. From the full-participants (<i>n</i> = 286), the overall participants (<i>n</i> = 421) and from the general population ≥ 65 years of Luxembourg (source: Statec 2001, <i>n</i> = 57,230). For this criteria, the overall participants (<i>p</i> < 0.0001) as well as the group of full-participants (<i>p</i> < 0.0001), were significantly different from the Luxembourgish seniors (Chi-squared test).</p

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