Vitamine K et fonctions cognitives chez la personne âgée en santé : une approche épidémiologique nutritionnelle

La vitamine K fait l’objet d’un intérêt croissant en regard du rôle qu’elle peut jouer dans la santé humaine hormis celui bien établi dans la coagulation sanguine. De plus en plus d’études expérimentales lui confèrent des fonctions dans le système nerveux central, particulièrement dans la synthèse des sphingolipides, l’activation de la protéine vitamine K-dépendante Gas6 et la protection contre les dommages oxydatifs. Toutefois, il demeure beaucoup moins bien établi si la perturbation de ces fonctions peut conduire à des déficits cognitifs. L’objectif principal de cette thèse est de vérifier l’hypothèse selon laquelle le statut vitaminique K des personnes âgées en santé est un déterminant de la performance cognitive. En vue de la réalisation de cet objectif, une meilleure compréhension des indicateurs du statut vitaminique K s’avérait nécessaire. Chacune des études présentées vise donc un objectif spécifique : 1) évaluer le nombre de rappels alimentaires de 24 heures non consécutifs nécessaire pour mesurer l’apport habituel de vitamine K des personnes âgées; 2) évaluer la valeur d’une seule mesure de la concentration sérique de vitamine K comme marqueur de l’exposition à long terme; et 3) examiner l’association entre le statut vitaminique K et la performance cognitive des personnes âgées en santé de la cohorte québécoise NuAge. Trois dimensions cognitives ont été évaluées soient la mémoire épisodique verbale et non-verbale, les fonctions exécutives et la vitesse de traitement de l’information. Cette thèse présente la première étude appuyant l’hypothèse d’un rôle de la vitamine K dans la cognition chez les personnes âgées. Spécifiquement, la concentration sérique de vitamine K a été associée positivement à la performance en mémoire épisodique verbale, et plus particulièrement au processus de consolidation de la trace mnésique. En accord avec les travaux chez l’animal et l’action de la protéine Gas6 dans l’hippocampe, un rôle spécifique de la vitamine K à l’étape de consolidation est biologiquement plausible. Aucune association significative n’a été observée avec les fonctions exécutives et la vitesse de traitement de l’information. Parallèlement, il a été démontré qu’une mesure unique de la concentration sérique de vitamine K constitue une mesure adéquate de l’exposition à long terme à la vitamine K. De même, il a été établi que six à 13 rappels alimentaires de 24 heures sont nécessaires pour estimer précisément l’apport de vitamine K des personnes âgées en santé. Collectivement, les résultats de ces deux études fournissent des informations précieuses aux chercheurs permettant une meilleure interprétation des études existantes et une meilleure planification des études futures. Les résultats de cette thèse constituent une avancée importante dans la compréhension du rôle potentiel de la vitamine K dans le système nerveux central et renforce la nécessité qu’elle soit considérée en tant que facteur nutritionnel du vieillissement cognitif, en particulier chez les personnes traitées par un antagoniste de la vitamine K.There is an increasing interest in the potential roles of vitamin K in human health aside from the one well established in blood clotting. Notably, a growing number of experimental studies show that vitamin K has biological functions in the central nervous system, particularly in the synthesis of sphingolipids, the activation of the vitamin K-dependent protein Gas6, and the prevention of oxidative damage. However, it remains uncertain whether the disruption of these functions can lead to cognitive deficits. The main objective of this thesis is to test the hypothesis that vitamin K status is a determinant of cognitive performance in healthy older adults. In order to achieve this goal, a better understanding of vitamin K status indicators was needed. Accordingly, three studies are presented each aiming at a specific objective: 1) estimate the number of non-consecutive 24-hour dietary recalls needed to assess usual vitamin K intake; 2) determine whether a single measurement of serum vitamin K concentration is an adequate indicator of long-term vitamin K exposure; and 3) examine the association between vitamin K status and cognitive performance in healthy older adults from the Québec NuAge Study. Three cognitive domains were assessed namely verbal and non-verbal episodic memory, executive functions, and speed of processing. This thesis presents the first study providing support for a role of vitamin K in cognition in older adults. Specifically, serum vitamin K concentration was positively associated with performance in verbal episodic memory, particularly in the consolidation process of the memory trace. Consistent with rodent studies and the action of the protein Gas6 in the hippocampus, a specific role of vitamin K in memory consolidation is biologically plausible. No significant association was observed with executive functions and speed of processing. Additionally, it was established that a single measurement of serum vitamin K concentration is adequate for assessing long-term vitamin K exposure in healthy older adults. Similarly, it was determined that six to 13 24-hour dietary recalls are needed to accurately assess usual vitamin K intake. Collectively, both studies provide valuable information to researchers for better interpretation of existing studies and planning future ones. Results from this thesis constitute an important step in the understanding of the potential role of vitamin K in the central nervous system, emphasizing the need to consider this micronutrient as a nutritional factor of cognitive aging, especially among those treated with vitamin K antagonists

Associations between circulating cardiovascular disease risk factors and cognitive performance in cognitively healthy older adults from the NuAge study

IntroductionCardiovascular disease risk factors (CVRFs) contribute to the development of cognitive impairment and dementia.MethodsThis study examined the associations between circulating CVRF biomarkers and cognition in 386 cognitively healthy older adults (mean age = 78 ± 4 years, 53% females) selected from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge). Memory, executive function, and processing speed were assessed at baseline and 2-year follow-up. CVRF biomarkers included total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides, glucose, insulin, high sensitivity C-reactive protein (hs-CRP), homocysteine, protein carbonyls, and cortisol. Linear mixed models were used to determine associations between individual CVRF biomarkers and cognition at both time points.ResultsHDL-C was most consistently associated with cognition with higher values related to better performance across several domains. Overall, stronger and more consistent relationships between CVRF biomarkers and cognition were observed in females relative to males.DiscussionFindings suggest that increases in the majority of circulating CVRFs are not associated with worse cognition in cognitively healthy older adults

Aging all over the place : a multidisciplinary framework, that considers place and life trajectories of older adults within their communities

Abstract : Purpose This conceptual paper describes Aging All Over the Place (AAOP), a federative framework for action, research and policy that considers older adults’ diverse experiences of place and life trajectories, along with person-centered care. Design/methodology/approach The framework was developed through group discussions, followed by an appraisal of aging models and validation during workshops with experts, including older adults. Findings Every residential setting and location where older adults go should be considered a ‘place’, flexible and adaptable enough so that aging in place becomes aging all over the place. Healthcare professionals, policymakers and researchers are encouraged to collaborate around four axes: 1) biopsychosocial health and empowerment; 2) welcoming, caring, mobilized, and supportive community; 3) spatiotemporal life and care trajectories; and 4) out-of-home care and services. When consulted, a Seniors Committee showed appreciation for flexible person-centered care, recognition of life transitions and care trajectories, and meaningfulness of the name. Originality Building on the introduction of an ecological experience of aging, AAOP broadens the concept of care as well as the political and research agenda by greater integration of community and clinical actions. AAOP also endeavors to avoid patronizing older adults and engage society in strengthening circles of benevolence surrounding older adults, regardless of their residential setting. AAOP’s applicability is evidenced by existing projects that shared its approach. Social implications Population aging and the pandemic call for intersectoral actions and for stakeholders beyond healthcare to act as community leaders. AAOP proposes opportunities to connect environmental determinants of health and person-centered care

a pooled analysis of four longitudinal aging cohorts

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.BACKGROUND: Dietary protein may slow the decline in muscle mass and function with aging, making it a sensible candidate to prevent or modulate disability progression. At present, studies providing reliable estimates of the association between protein intake and physical function, and its interaction with physical activity (PA), in community-dwelling older adults are lacking. OBJECTIVES: We investigated the longitudinal relation between protein intake and physical function, and the interaction with PA. METHODS: We undertook a pooled analysis of individual participant data from cohorts in the PROMISS (PRevention Of Malnutrition In Senior Subjects in the European Union) consortium (the Health Aging and Body Composition Study, Quebec Longitudinal Study on Nutrition and Successful Aging, Longitudinal Aging Study Amsterdam, and Newcastle 85+) in which 5725 community-dwelling older adults were followed up to 8.5 y. The relation between protein intake and walking speed was determined using joint models (linear mixed-effects and Cox proportional hazards models) and the relation with mobility limitation was investigated using multistate models. RESULTS: Higher protein intake was modestly protective of decline in walking speed in a dose-dependent manner [e.g., protein intake ≥1.2 compared with 0.8 g/kg adjusted body weight (aBW)/d: β = 0.024, 95% CI: 0.009, 0.032 SD/y], with no clear indication of interaction with PA. Participants with protein intake ≥0.8 g/kg aBW/d had also a lower likelihood of incident mobility limitation, which was observed for each level of PA. This association seemed to be dose-dependent for difficulty walking but not for difficulty climbing stairs. No associations between protein intake and other mobility limitations transitions were observed. CONCLUSIONS: Higher daily protein intake can reduce physical function decline not only in older adults with protein intake below the current RDA of 0.8 g/kg BW/d, but also in those with a protein intake that is already considered sufficient. This dose-dependent association was observed for each level of PA, suggesting no clear synergistic association between protein intake and PA in relation to physical function.publishersversionpublishe

Prevalence of protein intake below recommended in community‐dwelling older adults: a meta‐analysis across cohorts from the PROMISS consortium

European Horizon 2020 PROMISS Project ‘PRevention Of Malnutrition In Senior Subjects in the EU’, (grant agreement no. 678732). The content only reflects the author’s view and the commission is not responsible for any use that may be made of the information it contains.Background: Lower protein intake in older adults is associated with loss of muscle mass and strength. The present study aimed to provide a pooled estimate of the overall prevalence of protein intake below recommended (according to different cut-off values) among community-dwelling older adults, both within the general older population and within specific subgroups. Methods: As part of the PRevention Of Malnutrition In Senior Subjects in the EU (PROMISS) project, a meta-analysis was performed using data from four cohorts (from the Netherlands, UK, Canada, and USA) and four national surveys [from the Netherlands, Finland (two), and Italy]. Within those studies, data on protein and energy intake of community-dwelling men and women aged ≥55 years were obtained by either a food frequency questionnaire, 24 h recalls administered on 2 or 3 days, or food diaries administered on 3 days. Protein intake below recommended was based on the recommended dietary allowance of 0.8 g/kg body weight (BW)/d, by using adjusted BW (aBW) instead of actual BW. Cut-off values of 1.0 and 1.2 were applied in additional analyses. Prevalences were also examined for subgroups according to sex, age, body mass index (BMI), education level, appetite, living status, and recent weight loss. Results: The study sample comprised 8107 older persons. Mean ± standard deviation protein intake ranged from 64.3 ± 22.3 (UK) to 80.6 ± 23.7 g/d [the Netherlands (cohort)] or from 0.94 ± 0.38 (USA) to 1.17z ± 0.30 g/kg aBW/d (Italy) when related to BW. The overall pooled prevalence of protein intake below recommended was 21.5% (95% confidence interval: 14.0–30.1), 46.7% (38.3–55.3), and 70.8% (65.1–76.3) using the 0.8, 1.0, and 1.2 cut-off value, respectively. A higher prevalence was observed among women, individuals with higher BMI, and individuals with poor appetite. The prevalence differed only marginally by age, education level, living status, and recent weight loss. Conclusions: In community-dwelling older adults, the prevalence of protein intake below the current recommendation of 0.8 g/kg aBW/d is substantial (14–30%) and increases to 65–76% according to a cut-off value of 1.2 g/kg aBW/d. To what extent the protein intakes are below the requirements of these older people warrants further investigation.publishersversionpublishe

Multidimensional associations between nutrient intake and healthy ageing in humans

Background Little is known about how normal variation in dietary patterns in humans affects the ageing process. To date, most analyses of the problem have used a unidimensional paradigm, being concerned with the effects of a single nutrient on a single outcome. Perhaps then, our ability to understand the problem has been complicated by the fact that both nutrition and the physiology of ageing are highly complex and multidimensional, involving a high number of functional interactions. Here we apply the multidimensional geometric framework for nutrition to data on biological ageing from 1560 older adults followed over four years to assess on a large-scale how nutrient intake associates with the ageing process. Results Ageing and age-related loss of homeostasis (physiological dysregulation) were quantified via the integration of blood biomarkers. The effects of diet were modelled using the geometric framework for nutrition, applied to macronutrients and 19 micronutrients/nutrient subclasses. We observed four broad patterns: (1) The optimal level of nutrient intake was dependent on the ageing metric used. Elevated protein intake improved/depressed some ageing parameters, whereas elevated carbohydrate levels improved/depressed others; (2) There were non-linearities where intermediate levels of nutrients performed well for many outcomes (i.e. arguing against a simple more/less is better perspective); (3) There is broad tolerance for nutrient intake patterns that don’t deviate too much from norms (‘homeostatic plateaus’). (4) Optimal levels of one nutrient often depend on levels of another (e.g. vitamin E and vitamin C). Simpler linear/univariate analytical approaches are insufficient to capture such associations. We present an interactive tool to explore the results in the high-dimensional nutritional space. Conclusion Using multidimensional modelling techniques to test the effects of nutrient intake on physiological dysregulation in an aged population, we identified key patterns of specific nutrients associated with minimal biological ageing. Our approach presents a roadmap for future studies to explore the full complexity of the nutrition-ageing landscape

| [Afrique du Sud: défis et succès du confinement liés au COVID-19]

At the beginning of March 2020, South Africa (59 million inhabitants) was hit by the pandemic of COVID-19 and soon became the most affected country in Africa by the SARS-CoV-2 virus. From one single case on March 5th, the number of cases increased rapidly, forcing the South-African Government to swiftly react and place the country under strict lockdown for six weeks. The strategy of the South African Government bore fruits with a contained spread of the virus. If the number of positive cases at the end of the lockdown reached 5647, the number of fatal casualties was limited to 103 deaths. The lockdown was overall well respected, even if serious problems of food supply soon occurred in informal settlements, leading to riots and confrontation with security forces. Indeed, populations were obedient, but not being able to practice sport or outdoors activities appeared heavy

Prospective associations of protein intake parameters with muscle strength and physical performance in community-dwelling older men and women from the Quebec NuAge cohort

BACKGROUND: Dietary protein has been related to muscle function in aging. Beyond total intake, parameters such as protein distribution across meals might also be important. OBJECTIVES: We aimed to examine prospective associations of different protein intake parameters with muscle strength and physical performance in community-dwelling older men and women. METHODS: In total, 524 men and 574 women aged 67-84 y at baseline (T1) were followed annually for 3 y (T2, T3, T4). Outcomes included handgrip strength (kPa), knee extensor strength (kg), and physical performance (Timed Up and Go, s) at T4, and their 3-y changes (T4 minus T1). Protein intake parameters were assessed using nine 24-h recalls collected over 3 y (T1, T2, T3) and included daily total intake (g/d), number of protein-providing meals and snacks, and protein distribution across meals (expressed as CV). Associations were examined by multivariable linear regression models including all protein intake parameters simultaneously. Also, the optimal protein dose (g) per meal for the maximum effect size of total daily intake was determined. RESULTS: Higher daily protein intake was associated with better knee extensor strength and physical performance at T4 in both sexes and less physical performance decline in women. Optimal protein doses per meal were 30-35 g in men and 35-50 g in women for these outcomes. In men, more uneven protein distribution was associated with better physical performance at T4 and less handgrip strength decline. In women, a higher number of protein-providing snacks was associated with better handgrip strength and knee extensor strength at T4 and less handgrip strength decline. In neither sex was number of protein-providing meals associated with outcomes. CONCLUSIONS: Higher daily protein intake, up to 30-50 g protein/meal, may contribute to better knee extensor strength and physical performance in generally well-functioning older men and women. More aspects of protein intake may contribute to muscle strength and physical performance than solely the daily quantity, notably the protein dose per meal

Dietary Vitamin K Intake Is Associated with Cognition and Behaviour among Geriatric Patients: The CLIP Study

Our objective was to determine whether dietary vitamin K intake was associated with cognition and behavior among older adults. 192 consecutive participants ≥65 years, recruited in the cross-sectional CLIP (Cognition and LIPophilic vitamins) study, were separated into two groups according to the tertiles of dietary phylloquinone intake (i.e., lowest third below 207 µg/day versus the other two thirds combined). Daily dietary phylloquinone intake was estimated from 50-item interviewer-administered food frequency questionnaire. Cognition was assessed with Mini-Mental State Examination (MMSE); behaviour with Frontotemporal Behavioral Rating Scale (FBRS). Age, gender, social problems, education, body mass index (BMI), comorbidities, history of stroke, use vitamin K antagonists, inadequate fatty fish intake, serum thyroid-stimulating hormone (TSH), vitamin B12, albumin, and estimated glomerular filtration rate were used as confounders. Compared to participants in the lowest third of dietary phylloquinone intake (n = 64), those with higher intake had higher (i.e., better) mean MMSE score (22.0 ± 5.7 versus 19.9 ± 6.2, p = 0.024) and lower (i.e., better) FBRS score (1.5 ± 1.2 versus 1.9 ± 1.3, p = 0.042). In multivariate linear regressions, log dietary phylloquinone intake was positively associated with MMSE score (adjusted β = 1.66, p = 0.013) and inversely associated with FBRS score (adjusted β = −0.33, p = 0.037). Specifically, log dietary phylloquinone intake correlated negatively with FBRS subscore of physical neglect (r = −0.24, p = 0.001). Higher dietary phylloquinone intake was associated with better cognition and behavior among older adults