The association between grip strength and carotid intima media thickness: A Mendelian randomization analysis of the Canadian Longitudinal Study on Aging.

BACKGROUND: Several two-sample Mendelian randomization studies have reported discordant results concerning the association between grip strength and cardiovascular disease, possibly due to the number of instrumental variables used, pleiotropic bias, and/ or effect modification by age and sex. METHODS: We conducted a sex- and age-stratified one-sample Mendelian randomization study in the Canadian Longitudinal Study on Aging. We investigated whether grip strength is associated with carotid intima media thickness (cIMT), a marker of vascular atherosclerosis event risk, using eighteen single nucleotide polymorphisms (SNP) identified as specifically associated with grip strength. RESULTS: A total of 20,258 participants of self-reported European ancestry were included in the analytic sample. Our Mendelian randomization findings suggest a statistically significant association between grip strength and cIMT (MR coefficient of 0.02 (95% CI: 0.01, 0.04)). We found no statistically significant differences between sexes (p-value = 0.201), or age groups [(≤ 60 years old versus >60 years old); p-value = 0.421]. CONCLUSION: This study provides evidence that grip strength is inversely associated with cIMT. Our one-sample MR study design allowed us to demonstrate that there is no evidence of heterogeneity of effects according to age group or biological sex.

Evidence for protein leverage on total energy intake, but not body mass index, in a large cohort of older adults.

BACKGROUND: Protein leverage (PL) is the phenomenon of consuming food until absolute intake of protein approaches a 'target value', such that total energy intake (TEI) varies passively with the ratio of protein: non-protein energy (fat + carbohydrate) in the diet. The PL hypothesis (PLH) suggests that the dilution of protein in energy-dense foods, particularly those rich in carbohydrates and fats, combines with protein leverage to contribute to the global obesity epidemic. Evidence for PL has been reported in younger adults, children and adolescents. This study aimed to test for PL and the protein leverage hypothesis (PLH) in a cohort of older adults. METHODS: We conducted a retrospective analysis of dietary intake in a cohort of 1699 community-dwelling older adults aged 67-84 years from the NuAge cohort. We computed TEI and the energy contribution (EC) from each macronutrient. The strength of leverage of macronutrients was assessed through power functions ([Formula: see text]). Body mass index (BMI) was calculated, and mixture models were fitted to predict TEI and BMI from macronutrients' ECs. RESULTS: In this cohort of older adults, 53% of individuals had obesity and 1.5% had severe cases. The mean TEI was 7673 kJ and macronutrients' ECs were 50.4%, 33.2% and 16.4%, respectively for carbohydrates, fat, and protein. There was a strong negative association (L = -0.37; p < 0.001) between the protein EC and TEI. Each percent of energy intake from protein reduced TEI by 77 kJ on average, ceteris paribus. However, BMI was unassociated with TEI in this cohort. CONCLUSIONS: Findings indicate clear evidence for PL on TEI, but not on BMI, likely because of aging, body composition, sarcopenia, or protein wasting.

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

Introduction: Cardiovascular disease risk factors (CVRFs) contribute to the development of cognitive impairment and dementia. Methods: This 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. Results: HDL-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. Discussion: Findings suggest that increases in the majority of circulating CVRFs are not associated with worse cognition in cognitively healthy older adults.

Systematic review of research barriers, facilitators, and stakeholders in long-term care and geriatric settings, and a conceptual mapping framework to build research capacity.

BACKGROUND: Older adults are underrepresented in research. Heterogeneity of research processes in this population, specifically in long-term care (LTC) and geriatric acute care (GAC), is not well described and may impede the design, planning, and conduct of research. In this study, we identified, quantified, and mapped stakeholders, research stages, and transversal themes of research processes, to develop a mapping framework to improve research capacity by better characterizing this heterogeneity. METHODS: Multicomponent mixed methods study. An environmental scan was used to initiate a preliminary framework. We conducted a systematic literature search on processes, barriers, and methods for clinical research in GAC and LTC to extract and update stakeholders, research stages, and themes. Importance and interactions of elements were synthesized via heatmaps by number of articles, mentions, and content intersections. RESULTS: For our initial framework and environmental scan, we surveyed 24 stakeholders. Of 9277 records, 68 articles were included in our systematic review and allowed us to identify 12 stakeholders, 13 research stages, 17 transversal themes (either barriers, facilitators, general themes, or recommendations), and 1868 intersections. Differences in relative importance between LTC and GAC emerged for stakeholders (staff, managers vs. caregivers, ethics committees), and for research stages (funding, facility recruitment vs. ethics, individual recruitment). Crucial themes according to specific stakeholders were collaboration for the research team; communication, trust, and human resources for managers; heterogeneity for patients and residents. A heatmap framework synthesizing vital stakeholders and themes per research stage was generated. CONCLUSIONS: We identified and quantified the interactions between stakeholders, stages, and themes to characterize heterogeneity in LTC and GAC research. Our framework may serve as a blueprint to co-construct and improve each stage of the research process.

Frailty, Cognitive Impairment, and Incident Major Neurocognitive Disorders: Results of the NuAge Cohort Study.

BACKGROUND: Frailty is associated with an increased risk of major neurocognitive disorders (MNCD). OBJECTIVE: This study aims to compare the Fried physical model and the CARE deficit accumulation model for their association with incident major neurocognitive disorders (MNCD), and to examine how the addition of cognitive impairment to these frailty models impacts the incidence in community-dwelling older adults. METHODS: A subset of community dwellers (n = 1,259) who participated in the "Quebec Longitudinal Study on Nutrition and Successful Aging" (NuAge) were selected in this Elderly population-based observational cohort study with 3 years of follow-up. Fried and CARE frailty stratifications into robust, pre-frail and frail groups were performed using the NuAge baseline assessment. Incident MNCD (i.e., Modified Mini Mental State (3MS) score < 79/100 and Instrumental Activity Daily Living (IADL) score < 6/8) were collected each year over a 3-year follow-up period. RESULTS: A greater association with incident MNCD of the CARE frail state was observed with an increased predictive value when combined with cognitive impairment in comparison to Fried's one, the highest incidences being observed using the robust state as the reference. Results with the Fried frail state were more heterogenous, with no association with the frail state alone, whereas cognitive impairment alone showed the highest significant incidence. CONCLUSION: The association of the CARE frail state with cognitive impairment increased the predictive value of MNCD, suggesting that the CARE frailty model may be of clinical interest when screening MCND in the elderly population.

Serum metabolomic adaptations following a 12-week high-intensity interval training combined to citrulline supplementation in obese older adults.

Physical activity and nutrition play important roles in preventing adverse health outcomes that accompany aging. It has been shown that high-intensity interval training (HIIT) combined with citrulline (CIT) supplementation can improve physical and functional capacities. The aim of this study was to evaluate serum metabolites following a 12-week HIIT combined or not with CIT in obese older adults, and to correlate the metabolic changes with clinico-biological parameters changes. Eighty-six obese older adults completed a 12-week HIIT program combined with a 10 g daily supplementation of either CIT or placebo (PLA) during a double-blinded randomized interventional trial. Only participants with blood samples at T0 (before the intervention) and/or T12 (after the intervention) were included in our sub-analysis (HIIT-PLA-T0: n = 44 and HIIT-PLA-T12: n = 28; HIIT-CIT-T0: n = 39 and HIIT-CIT-T12: n = 42). Serum samples were analyzed by different liquid or gas phase chromatography methods coupled to mass spectrometry. Among the identified metabolites, 44 changed significantly following the 12-week intervention (Time effect), and 10 of them were more affected when HIIT was combined with CIT (Time × Supp effect). Arginine increased significantly due to the 12-week intervention. Correlation analyses demonstrated that decreased triglyceride (TG) (16:1/18:1/16:0) and aspartic acid significantly correlated with a reduction of adiposity-related parameters (fat mass, leg lean mass, leptin, total triglycerides and low-density lipoprotein). Arginine, TG (16:1/18:1/16:0) and aspartic acid might constitute biomarkers of cardiometabolic health and adiposity. Further studies are needed to confirm these associations and understand the underlying mechanisms.Highlights A 12-week intervention involving high-intensity interval training (HIIT) with or without citrulline (CIT) supplementation induced adaptations in the serum metabolome of obese older adults through significant changes in 44 metabolites.Changes in 23 metabolites were observed when a CIT supplementation was administered along with a 12-week HIIT intervention.TG (16:1/18:1/16:0) correlated with several adiposity parameters including leptin, triglycerides, legs lean mass.Aspartic acid correlated with several adiposity parameters including leptin, LDL cholesterol as well as android, arms and trunk fat mass.

Serum Metabolome Adaptations Following 12 Weeks of High-Intensity Interval Training or Moderate-Intensity Continuous Training in Obese Older Adults.

Physical activity can be effective in preventing some of the adverse effects of aging on health. High-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) are beneficial interventions for the quality of life of obese older individuals. The understanding of all possible metabolic mechanisms underlying these beneficial changes has not yet been established. The aim of this study was to analyze changes in the serum metabolome after 12 weeks of HIIT and MICT in obese older adults. Thirty-eight participants performed either HIIT (n = 26) or MICT (n = 12) three times per week for 12 weeks. Serum metabolites as well as clinical and biological parameters were assessed before and after the 12-week intervention. Among the 364 metabolites and ratio of metabolites identified, 51 metabolites changed significantly following the 12-week intervention. Out of them, 21 significantly changed following HIIT intervention and 18 significantly changed following MICT. Associations with clinical and biological adaptations revealed that changes in acyl-alkyl-phosphatidylcholine (PCae) (22:1) correlated positively with changes in handgrip strength in the HIIT group (r = 0.52, p < 0.01). A negative correlation was also observed between 2-oxoglutaric acid and HOMA-IR (r = -0.44, p < 0.01) when considering both groups together (HIIT and MICT). This metabolite also correlated positively with quantitative insulin-sensitivity check index (QUICKI) in both groups together (r = 0.46, p < 0.01) and the HIIT group (r = 0.51, p < 0.01). Additionally, in the MICT group, fumaric acid was positively correlated with triglyceride levels (r = 0.73, p < 0.01) and acetylcarnitine correlated positively with low-density lipoprotein (LDL) cholesterol (r = 0.81, p < 0.01). These four metabolites might represent potential metabolites of interest concerning muscle strength, glycemic parameters, as well as lipid profile parameters, and hence, for a potential healthy aging. Future studies are needed to confirm the association between these metabolites and a healthy aging.

Olfactory Dysfunction Associated with Cognitive Decline in an Elderly Population.

BACKGROUND: In many neurological disorders, including Alzheimer disease, early olfactory dysfunction is observed. OBJECTIVE: In order to determine if deficits in olfactory memory are present in the elderly and if olfactory dysfunction correlates with cognitive impairment in the aging population, olfactory testing has been done on seniors from the NuAge cohort accepting to participate in the Olfactory Response Cognition and Aging (ORCA) secondary sub-study. The t-Mini Mental Statement Examination and the Telephone Interview for Cognitive Status tests were done to assess cognition levels. RESULTS: Overall, 94% of the ORCA cohort displayed olfactory dysfunction. Deficits in olfactory memory were also present. A correlation was observed between olfactory function and cognitive test scores. Moreover, in women who smoked, there was an association between olfactory memory and cognitive scores. CONCLUSION: Our results suggest that olfactory dysfunction may predict impending cognitive decline and highlights the need for olfactory training in seniors to improve olfaction and overall well-being.

Motoric cognitive risk syndrome and incident hospitalization in Quebec's older population: Results of the NuAge cohort study.

Background: Screening older adults at risk of hospitalization is essential to prevention of this adverse event. Motoric cognitive risk syndrome (MCR) has been associated with incident dementia and falls, which are both risk factors of hospitalization. There is no information on the association of MCR with incident hospitalization in older adults. Objective: The study aims to examine the association of MCR with incident hospitalization in community-dwelling older adults. Design: Quebec older population-based observational cohort study with 3 years of follow-up. Setting: Community dwellings. Subjects: A subset of 999 participants recruited in the NuAge study. Methods: Participants with MCR (i.e., with slow gait and cognitive complaint without dementia or motor disability) were identified at baseline assessment. Incident hospitalization (i.e., ≥1) and its recurrence (i.e., ≥2) were collected annually over a 3 year follow-up period. Results: The prevalence of MCR was 5.0% at baseline. The overall incidence of hospitalization was 29.0% and its recurrence 4.8%. MCR was associated with incident recurrent hospitalization [adjusted Hazard Ratio (aHR) = 2.58 with 95% Confidence Interval (CI) = (1.09-6.09) and P = 0.031], but not with incident hospitalization [aHR = 1.48, with 95%CI = (0.95-2.28) and P = 0.081]. Conclusion: MCR is associated with incident recurrent hospitalization in NuAge participants, suggesting that MCR may be of clinical interest for screening individuals at risk for hospitalization in Quebec's older population.

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.

Protein intake, physical activity and grip strength in European and North American community-dwelling older adults: a pooled analysis of individual participant data from four longitudinal ageing cohorts.

INTRODUCTION: Higher dietary protein, alone or in combination with physical activity (PA), may slow the loss of age-related muscle strength in older adults. We investigated the longitudinal relationship between protein intake and grip strength, and the interaction between protein intake and PA, using four longitudinal ageing cohorts. METHODS: Individual participant data from 5584 older adults (52% women; median: 75, IQR: 71.6, 79.0 years) with up to 8.5 years (mean: 4.9, SD: 2.3 years) of follow-up from the Health ABC, NuAge, LASA and Newcastle 85+ cohorts were pooled. Baseline protein intake was assessed with food frequency questionnaires and 24h recalls and categorized into <0.8, 0.8-<1.0, 1.0-<1.2 and ≥1.2 g/kg adjusted body weight (aBW)/d. The prospective association between protein intake, its interaction with PA, and grip strength (sex- and cohort-specific) was determined using joint models (hierarchical linear mixed effects and a link function for Cox proportional hazards models). RESULTS: Grip strength declined on average by 0.018 SD (95%CI: -0.026, -0.006) every year. No associations were found between protein intake, measured at baseline, and grip strength, measured prospectively, or rate of decline of grip strength in models adjusted for sociodemographic, anthropometric, lifestyle and health variables (e.g., protein intake ≥1.2 vs <0.8 g/kg aBW/d: ß= -0.003, 95%CI: -0.014,0.005 SD per year). There also was no evidence of an interaction between protein intake and PA. CONCLUSIONS: We failed to find evidence in this study to support the hypothesis that higher protein intake, alone or in combination with higher PA, slowed the rate of grip strength decline in older adults.

Clinical and Biological Adaptations in Obese Older Adults Following 12-Weeks of High-Intensity Interval Training or Moderate-Intensity Continuous Training.

Sarcopenia and obesity are considered a double health burden. Therefore, the implementation of effective strategies is needed to improve the quality of life of older obese individuals. The aim of this study was to compare the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on functional capacities, muscle function, body composition and blood biomarkers in obese older adults. Adipose tissue gene expression and markers of muscle mitochondrial content and quality control involved in exercise adaptations were also investigated. Sixty-eight participants performed either HIIT (n = 34) on an elliptical trainer or MICT (n = 34) on a treadmill, three times per week for 12 weeks. HIIT produced significantly higher benefits on some physical parameters (six-minute walking test (HIIT: +12.4% vs. MICT: +5.2%); step test (HIIT: +17.02% vs. MICT: +5.9%); ten-repetition chair test (HIIT: -17.04% vs. MICT: -4.7%)). Although both HIIT and MICT led to an improvement in lower limb power (HIIT: +25.2% vs. MICT: +20.4%), only MICT led to higher improvement in lower limb muscle strength (HIIT: +4.3% vs. MICT: +23.2%). HIIT was more beneficial for increasing total lean body mass (HIIT: +1.58% vs. MICT: -0.81%), while MICT was more effective for decreasing relative gynoid fat mass (HIIT: -1.09% vs. MICT: -4.20%). Regarding adipose tissue gene expression, a significant change was observed for cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) in the HIIT group (A.U; HIIT at T0: 32.10 ± 39.37 vs. HIIT at T12: 48.2 ± 59.2). Mitochondrial transcription factor A (TFAM) content, a marker of mitochondrial biogenesis, increased significantly following HIIT (+36.2%) and MICT (+57.2%). A significant increase was observed in the HIIT group for Translocase of Outer Membrane 20 (TOM20; +54.1%; marker of mitochondrial content), Mitofusin-2 (MFN2; +71.6%; marker of mitochondrial fusion) and Parkin RBR E3 Ubiquitin Protein Ligase (PARKIN; +42.3%; marker of mitophagy). Overall, our results indicate that even though MICT (walking on treadmill) and HIIT (on an elliptical) are effective intervention strategies in obese older adults, HIIT appears to have slightly more beneficial effects. More specifically, HIIT led to higher improvements than MICT on functional capacities, lean mass and skeletal muscle markers of mitochondrial content, fusion, and mitophagy. Thus, MICT but also HIIT (time-efficient training) could be recommended as exercise modalities for obese older adults to maintain or improve mobility, health and quality of life.

Methylmalonic acid analysis using urine filter paper samples to screen for metabolic vitamin B12 deficiency in older adults.

Aim: Methylmalonic acid (MMA) analysis in urine represents a noninvasive approach to screening for vitamin B12 deficiency in older adults. A method allowing the analysis of MMA/creatinine in fasting urine collected on filter paper was developed/validated. Method: Dry urine specimens were eluted using a solution containing internal standards, filtrated and analyzed by ultra-performance LC-MS/MS. Results: The method allowed the chromatographic separation of MMA from succinic acid. Dried urine samples were stable for 86 days at room temperature. The MMA/creatinine ratios measured in urine collected on filter paper were highly correlated with values derived from the corresponding liquid specimens. Conclusion: This robust filter paper method might greatly improve the accessibility and cost-effectiveness of vitamin B12 deficiency screening in older adults.

CARE frailty e-health scale: Association with incident adverse health outcomes and comparison with the Cardiovascular Health Study frailty scale in the NuAge cohort.

BACKGROUND: This study examines and compares CARE and Cardiovascular Health Study (CHS) frailty states (i.e., robust, prefrail and frail) for their association with incident adverse health outcomes, including falls, depression, cognitive and functional decline, major neurocognitive disorders, hospitalization and mortality in community-dwelling older adults living in the province of Quebec (Canada). METHODS: A subset of individuals (n = 1098) who participated in "Nutrition as a determinant of successful aging: The Quebec longitudinal study" (NuAge), which is an elderly population-based observational cohort study with 3 years of follow-up, were selected. CARE and CHS frailty states were determined using the NuAge baseline assessment. Incident falls (i.e., ≥1, ≥2 and severe falls), depression (i.e., 30-item Geriatric Depression Scale score > 10/30), decline in cognition (i.e., Modified Mini Mental State (3MS) score < 79/100) and functionality (i.e., Activity Daily Living (ADL) score ≤ 3/4 and an Instrumental Activity Daily Living (IADL) score ≤ 6/8), major neurocognitive disorders (i.e., 3MS score < 79/100 and IADL score < 6/8), hospitalization and mortality were annually recorded over a 3-year follow-up period. RESULTS: 66.8% and 23.6% of participants were classified as pre-frail and frail with CARE respectively, whereas this distribution of frailty states differed with CHS (47.9% and 8.4%). There were significant associations of CARE pre-frail and frail states with all incident adverse health outcomes, the lowest odds ratio (OR) being reported with falls and the highest with cognitive decline (OR ranging from 1.63 to 12.85 with P ≤ 0.032). All ORs of the CARE frailty states were greater than those of the CHS, except for frail participants with IADL decline (OR = 4.92 for CARE versus OR = 9.62 for CHS). CONCLUSIONS: CARE frail states were associated with incident adverse health outcomes and these associations were greater than with CHS, suggesting that the CARE scale is of clinical interest when screening for frailty and related adverse health outcomes in the elderly population.

Serum ω-3 Fatty Acids and Cognitive Domains in Community-Dwelling Older Adults from the NuAge Study: Exploring the Associations with Other Fatty Acids and Sex.

BACKGROUND: Omega-3 (n-3) PUFAs are suggested to play a role in the prevention of cognitive decline. The evidence may be inconsistent due to methodologic issues, including interrelations with other long-chain (14 or more carbons) fatty acids (LCFAs) and use of sex as a confounding factor rather than an effect modifier. OBJECTIVES: This study evaluated the association between serum n-3 PUFAs and performance across 4 cognitive domains, overall and by sex, while controlling for other LCFAs. METHODS: In total, 386 healthy older adults (aged 77.4 ± 3.8 y; 53% females) from the Quebec Longitudinal Study on Nutrition and Successful Aging underwent a cognitive evaluation and blood sampling. Verbal and nonverbal episodic memory, executive functioning, and processing speed were evaluated. Serum LCFA concentrations were measured by gas chromatography. LCFAs were grouped according to standard fatty acid classes and factor analysis using principal component analysis (FA-PCA). Multivariate linear regression models were performed, including unadjusted and adjusted models for other LCFAs. RESULTS: Higher n-3 PUFA concentrations were associated with better nonverbal memory and processing speed in fully adjusted models not including other LCFAs (ßs of 0.21 and 0.19, respectively). The magnitude of these associations varied when other LCFAs were entered in the model (ßs of 0.27 and 0.32, respectively) or when FA-PCA factors were considered (ßs of 0.27 and 0.21, respectively). Associations with verbal episodic memory were limited to higher concentrations of EPA, whereas there was no association between n-3 PUFAs and executive functioning. Higher n-3 PUFAs were associated with better verbal and nonverbal episodic memory in females and with better executive functioning and processing speed in males. CONCLUSIONS: These results suggest that other LCFAs should be considered when evaluating the association between n-3 PUFAs and cognitive performance in healthy older adults. Sex differences across cognitive domains warrant further investigation.

Impact of high-intensity interval training with or without l-citrulline on physical performance, skeletal muscle, and adipose tissue in obese older adults.

BACKGROUND: Aging is associated with a progressive decline in skeletal muscle mass and strength as well as an increase in adiposity. These changes may have devastating impact on the quality of life of older adults. Mitochondrial dysfunctions have been implicated in aging-related and obesity-related deterioration of muscle function. Impairments in mitochondrial quality control processes (biogenesis, fusion, fission, and mitophagy) may underlie this accumulation of mitochondrial dysfunction. High-intensity interval training (HIIT) was shown to improve muscle and mitochondrial function in healthy young and old adults and to improve body composition in obese older adults. Recent studies also positioned citrulline (CIT) supplementation as a promising intervention to counter obesity-related and aging-related muscle dysfunction. In the present study, our objectives were to assess whether HIIT, alone or with CIT, improves muscle function, functional capacities, adipose tissue gene expression, and mitochondrial quality control processes in obese older adults. METHODS: Eighty-one-old and obese participants underwent a 12 week HIIT with or without CIT on an elliptical trainer [HIIT-CIT: 20 men/25 women, 67.2 ± 5.0 years; HIIT-placebo (PLA): 18 men/18 women, 68.1 ± 4.1 years]. Handgrip and quadriceps strength, lower limb muscle power, body composition, waist circumference, and functional capacities were assessed pre and post intervention. Vastus lateralis muscle biopsies were performed in a subset of participants to quantify markers of mitochondrial content (TOM20 and OXPHOS subunits), biogenesis (TFAM), fusion (MFN1&2, OPA1), fission (DRP1), and mitophagy (Parkin). Subcutaneous abdominal adipose tissue biopsies were also performed to assess the expression of genes involved in lipid metabolism. RESULTS: HIIT-PLA and HIIT-CIT displayed improvements in functional capacities (P < 0.05), total (mean ± SD: HIIT-PLA: +1.27 ± 3.19%, HIIT-CIT: +1.05 ± 2.91%, P < 0.05) and leg lean mass (HIIT-PLA: +1.62 ± 3.85%, HIIT-CIT: +1.28 ± 4.82%, P < 0.05), waist circumference (HIIT-PLA: -2.2 ± 2.9 cm, HIIT-CIT: -2.6 ± 2.5 cm, P < 0.05), and muscle power (HIIT-PLA: +15.81 ± 18.02%, HIIT-CIT: +14.62 ± 20.02%, P < 0.05). Only HIIT-CIT decreased fat mass (-1.04 ± 2.42%, P < 0.05) and increased handgrip and quadriceps strength (+4.28 ± 9.36% and +10.32 ± 14.38%, respectively, P < 0.05). Both groups increased markers of muscle mitochondrial content, mitochondrial fusion, and mitophagy (P < 0.05). Only HIIT-CIT decreased the expression of the lipid droplet-associated protein CIDEA (P < 0.001). CONCLUSIONS: High-intensity interval training is effective in improving functional capacities, lean mass, muscle power, and waist circumference in obese older adults. HIIT also increases markers of mitochondrial biogenesis, mitochondrial fusion, and mitophagy. Importantly, adding CIT to HIIT results in a greater increase in muscle strength and a significant decrease in fat mass. The present study therefore positions HIIT combined with CIT as an effective intervention to improve the health status of obese older adults.

Vitamin B-12 Intake from Dairy but Not Meat Is Associated with Decreased Risk of Low Vitamin B-12 Status and Deficiency in Older Adults from Quebec, Canada.

BACKGROUND: Vitamin B-12 deficiency can result in irreversible neurologic damages. It is most prevalent among older adults (∼5%-15%), mainly due to impaired absorption. Vitamin B-12 bioavailability varies between food sources, so their importance in preventing deficiency may also vary. OBJECTIVES: Using the NuAge Database and Biobank, we examined the associations between vitamin B-12 intake (total and by specific food groups) and low vitamin B-12 status and deficiency in older adults. METHODS: NuAge-the Quebec Longitudinal Study on Nutrition and Successful Aging-included 1753 adults aged 67-84 y who were followed 4 y. Analytic samples comprised 1230-1463 individuals. Dietary vitamin B-12 intake was assessed annually using three 24-h dietary recalls. Vitamin B-12 status was assessed annually as low serum vitamin B-12 (<221 pmol/L), elevated urinary methylmalonic acid (MMA)/creatinine ratio (>2 µmol/mmol), and a combination of both (deficiency). Vitamin B-12 supplement users were excluded. Multilevel logistic regressions, adjusted for relevant confounders, were used. RESULTS: Across all study years, 21.8%-32.5% of participants had low serum vitamin B-12, 12.5%-17.0% had elevated urine MMA/creatinine, and 10.1%-12.7% had deficiency. Median (IQR) total vitamin B-12 intake was 3.19 µg/d (2.31-4.37). Main sources were "dairy" and "meat, poultry, and organ meats." The ORs (95% CIs) in the fifth quintile compared with the first of total vitamin B-12 intake were as follows: for low serum vitamin B-12, 0.52 (0.37, 0.75; P-trend < 0.0001); for elevated urine MMA/creatinine, 0.63 (0.37, 1.08; P-trend = 0.091); and for vitamin B-12 deficiency, 0.38 (0.18, 0.79; P-trend = 0.006). Similarly, ORs (95% CIs) in the fourth quartile compared with the first of dairy-derived vitamin B-12 intake were 0.46 (0.32, 0.66; P-trend < 0.0001), 0.51 (0.30, 0.87; P-trend = 0.006), and 0.35 (0.17, 0.73; P-trend = 0.003), respectively. No associations were observed with vitamin B-12 from "meat, poultry, and organ meats." CONCLUSIONS: Higher dietary vitamin B-12 intake, especially from dairy, was associated with decreased risk of low vitamin B-12 status and deficiency in older adults. Food groups might contribute differently at reducing risk of deficiency in older populations.

New onset, transient and stable motoric cognitive risk syndrome: Clinical characteristics and association with incidence of probable dementia in the NuAge cohort.

Background: Motoric cognitive risk syndrome (MCR) is a pre-dementia stage. The existence of stable and transient MCR, their related clinical characteristics and their association with incident dementia is a matter of debate. Objective: This study aims to examine the clinical characteristics and the time course associated with new onset, transient and stable MCR, and their association with incidence of probable dementia in community-dwelling older adults living in the province of Quebec (Canada). Design: Quebec elderly population-based observational cohort study with 3 years of follow-up. Setting: Community dwellers. Subjects: A subset of participants (n = 1,113) from the "Quebec Longitudinal Study on Nutrition and Successful Aging" (NuAge) cohort. Methods: Participants with MCR were identified at baseline and after 1 year of follow-up. Socio-demographic characteristics, 30-item Geriatric depression scale (GDS) score, cardiovascular risk factors and diseases were recorded at baseline. Incidence of probable dementia was measured at annual follow-up visits over a 3-year period. Results: Over the period of the first year of follow-up, the prevalence of MCR was 8.5% with 4.3% having new onset MCR, 2.8% transient MCR and 1.4% stable MCR. A higher 30-item GDS score was reported with new onset and transient MCR, and the highest prevalence of cerebrovascular diseases was shown with stable MCR compared to non-MCR participants (p < 0.05). MCR was associated with overall incidence of probable dementia, regardless of its status (Hazard Ratio ≥ 1.86, p ≤ 0.034). Conclusion: Greater prevalence of depressive symptoms and cerebrovascular diseases were reported, respectively, with new onset and transient MCR, and stable MCR. The association of MCR with incidence of probable dementia remains significant, regardless of MCR subtypes.

Late-Life Depressive Symptomatology, Motoric Cognitive Risk Syndrome, and Incident Dementia: The "NuAge" Study Results.

Background: Late-life depressive symptomatology and motoric cognitive risk syndrome (MCR) have independently been associated with an increased risk for incident dementia. This study aimed to examine the association of late-life depressive symptomatology, MCR, and their combination on incident dementia in community-dwelling older adults living in Quebec (Canada). Methods: The study was carried out in a subset of 1,098 community dwellers aged ≥65 years recruited in the "Nutrition as a determinant of successful aging: The Quebec longitudinal study" (NuAge), an observational prospective cohort study with 3 years follow-up. At baseline, MCR was defined by the association of subjective cognitive complaint with slow walking speed, and late-life depressive symptomatology with a 30-item Geriatric Depression Scale (GDS) score >5/30. Incident dementia, defined as a Modified Mini-Mental State score ≤79/100 test and Instrumental Activity Daily Living score <4/4, was assessed at each annual visit. Results: The prevalence of late-life depressive symptomatology only was 31.1%, of MCR only 1.8%, and the combination of late-life depressive symptomatology and MCR 2.4%. The combination of late-life depressive symptomatology and MCR at baseline was associated with significant overall incident dementia (odds ratio (OR) = 2.31 with P ≤ 0.001) but not for MCR only (OR = 3.75 with P = 0.186) or late-life depressive symptomatology only (OR = 1.29 with P = 0.276). Conclusions: The combination of late-life depressive symptomatology and MCR is associated with incident dementia in older community dwellers. The results suggested an interplay between late-life depressive symptomatology and MCR exposing them to an increased risk for dementia.

Multiplatform metabolomics for an integrative exploration of metabolic syndrome in older men.

BACKGROUND: Metabolic syndrome (MetS), a cluster of factors associated with risks of developing cardiovascular diseases, is a public health concern because of its growing prevalence. Considering the combination of concomitant components, their development and severity, MetS phenotypes are largely heterogeneous, inducing disparity in diagnosis. METHODS: A case/control study was designed within the NuAge longitudinal cohort on aging. From a 3-year follow-up of 123 stable individuals, we present a deep phenotyping approach based on a multiplatform metabolomics and lipidomics untargeted strategy to better characterize metabolic perturbations in MetS and define a comprehensive MetS signature stable over time in older men. FINDINGS: We characterize significant changes associated with MetS, involving modulations of 476 metabolites and lipids, and representing 16% of the detected serum metabolome/lipidome. These results revealed a systemic alteration of metabolism, involving various metabolic pathways (urea cycle, amino-acid, sphingo- and glycerophospholipid, and sugar metabolisms…) not only intrinsically interrelated, but also reflecting environmental factors (nutrition, microbiota, physical activity…). INTERPRETATION: These findings allowed identifying a comprehensive MetS signature, reduced to 26 metabolites for future translation into clinical applications for better diagnosing MetS. FUNDING: The NuAge Study was supported by a research grant from the Canadian Institutes of Health Research (CIHR; MOP-62842). The actual NuAge Database and Biobank, containing data and biologic samples of 1,753 NuAge participants (from the initial 1,793 participants), are supported by the Fonds de recherche du Québec (FRQ; 2020-VICO-279753), the Quebec Network for Research on Aging, a thematic network funded by the Fonds de Recherche du Québec - Santé (FRQS) and by the Merck-Frost Chair funded by La Fondation de l'Université de Sherbrooke. All metabolomics and lipidomics analyses were funded and performed within the metaboHUB French infrastructure (ANR-INBS-0010). All authors had full access to the full data in the study and accept responsibility to submit for publication.