A web-based multidomain lifestyle intervention with connected devices for older adults: research protocol of the eMIND pilot randomized controlled trial.

BACKGROUND: Multidomain interventions composed of nutritional counseling, exercise and cognitive trainings have shown encouraging results as effective preventive strategies delaying age-related declines. However, these interventions are time- and resource-consuming. The use of Information and Communication Technologies (ICT) might facilitate the translation from research into real-world practice and reach a massive number of people. AIM: This article describes the protocol of the eMIND study, a randomized controlled trial (RCT) using a web-based multidomain intervention for older adults. METHODS: One hundred and twenty older adults (≥ 65 years), with a spontaneous memory complaint, will be randomly assigned to a six-month web-based multidomain (nutritional counseling, physical and cognitive trainings) intervention group with a connected accelerometer (number of steps, energy expenditure), or to a control group with access to general information on healthy aging plus the accelerometer, but no access to the multidomain intervention. The main outcome is the feasibility/acceptability of the web-based intervention. Secondary clinical outcomes include: cognitive functions, physical performance, nutritional status and cost-effectiveness. RESULTS: We expect a high amount of adherers (ie, > 75% compliance to the protocol) to reflect the feasibility. Acceptability, assessed through interviews, should allow us to understand motivators and barriers to this ICT intervention. We also expect to provide data on its effects on various clinical outcomes and efficiency. CONCLUSION AND DISCUSSION: The eMIND study will provide crucial information to help developing a future and larger web-based multidomain lifestyle RCT, which should facilitate the translation of this ICT intervention from the research world into real-life clinical practice for the healthcare of older adults.

Drug treatment for diabetes in nursing home residents.

AIMS: The aim of this study was to describe drug treatment for diabetes in a large sample of nursing home residents and to compare subjects' health outcomes according to the anti-diabetic agents used. METHODS: The cross-sectional data of 6275 residents [average age 86 years (± 8.2); 73.7% women] from 175 nursing homes in France were analysed. Participants were divided into one of the following four groups: diabetes non-drug treatment, diabetes hypoglycaemic (e.g. insulins, sulphonylurea) treatment, diabetes non-hypoglycaemic (e.g. metformin) treatment and no diabetes. Group comparisons were made on functional ability (activities of daily living score) and on the prevalence of the following variables (yes vs. no): emergency department visits, falls and fractures. RESULTS: Of the participants, 1076 (17.1%) had diabetes: 222 participants in the non-drug treatment group, 722 in the hypoglycaemic group and 132 in the non-hypoglycaemic group. The remaining 5199 participants made up the group without diabetes. Insulin and metformin were used by 549 and 185 participants, respectively. Activities of daily living scores differed across the four groups, with those in the non-drug treatment group being the most disabled. Adjusted multivariate analyses showed that, compared with the group without diabetes, those in the hypoglycaemic group had a higher probability of emergency department visits (odds ratio 1.26, 95% CI 1.03-1.54) and increased the incidence rate ratios (1.02, 95% CI 1.00-1.04) of disability (activities of daily living score), whereas the non-hypoglycaemic group was not significantly associated with these outcomes. CONCLUSIONS: The use of hypoglycaemic drugs was associated with poor health outcomes in nursing home residents. Therefore, more attention must be paid to adapting anti-diabetic treatment in this complex population.

Construct and convergent validity and repeatability of the Questionnaire d'Activité Physique pour les Personnes Âgées (QAPPA), a physical activity questionnaire for the elderly.

OBJECTIVES: To investigate repeatability, and construct and convergent validity of the Questionnaire d'Activité Physique pour les Personnes Âgées (QAPPA), a self-reported physical activity questionnaire for the elderly. STUDY DESIGN: Cross-sectional and prospective (1-year follow-up) data from two postal surveys among members of the medical insurance scheme of the French national education system. METHODS: A questionnaire on general health and the QAPPA were sent out twice, with a 1-year interval. Participants were ≥60 years of age (sample size varied from 225 to 393 according to the analysis). Intraclass correlations, Bland-Altman plots (continuous variables) and kappa coefficients (categorical variable) were used for repeatability analyses. Comparison tests were performed (Wilcoxon rank sum test and Kruskal-Wallis test) for construct validity. Chi-squared test and correlation coefficients were used to establish the convergent validity of the QAPPA. RESULTS: The QAPPA had acceptable repeatability with a 1-year interval, with moderate test-retest correlation coefficients (from r = 0.46 to r = 0.64) and a fair-to-good kappa coefficient (κ = 0.44). It discriminated between individuals by age group (with younger persons being more physically active than older persons) and exercise behaviour (with regular exercisers being more active than non-exercisers). The QAPPA was negatively associated with decline in physical function and comorbidity, and was positively associated with self-reported health and satisfaction with body functioning. CONCLUSION: This study found that the QAPPA is a valid tool for assessing the physical activity of older adults. It could be used for research purposes as well as for epidemiological surveillance.

Body Composition, Physical Function, and Dietary Patterns in People from 20 to Over 80 Years Old.

OBJECTIVES: Diet may influence biochemical pathways involved in age-related changes in body composition and physical function. This study aimed to describe dietary patterns and their relationships with body composition, physical performance, and grip strength according to age and sex. DESIGN: Cross-sectional study. SETTING: Data were collected in the Clinical Research Center (CRC) of the Gérontopôle of the Centre Hospitalier Universitaire (CHU) of Toulouse or at participants' homes when unable to attend the research facilities. PARTICIPANTS: 470 (63% female) people with a median age of 56 (38 - 70) years. MEASUREMENTS: The "Mediterranean-like" (i.e., plant-based foods, dairy), "Animal products" (i.e., meat, processed meat, butter, refined starch), and "Sugar and fast food" (i.e., ultra-processed and sugary foods) dietary patterns were extracted by principal component analysis. Total and trunk fat mass indexes (kg/m²), and total and appendicular lean mass indexes (kg/m²) were assessed by DXA. The physical tests comprised gait speed (m/sec), chair rise (sec), the Short Physical Performance Battery test (/12 points), and handgrip strength (kg). The associations were explored through multivariate linear regressions by sex and age groups: ≥20 to <50, ≥50 to <65, and ≥65 years. RESULTS: Men and women had higher adherence to the "Sugar and fast food" diet in the youngest group. Middle-aged and older women adhered more to a "Mediterranean-like" diet. Men kept a "Sugar and fast food" diet when middle-aged and changed to the "Animal products" diet when ≥65 years. Higher adherence to the "Mediterranean-like" diet was associated with lower BMI, body fat, and lean mass in middle-aged men. Higher adherence to the "Animal products" diet was associated with higher lean mass in middle-aged women, more trunk fat in young men, lower strength in middle-aged men, and higher strength in older men. Higher adherence to the "Sugar and fast food" diet was associated with higher body fat in middle-aged men but lower body fat in older men. CONCLUSION: Diets composed of sugary foods, fast foods, and processed meat were associated with higher fat mass and lower strength. Men were more prone to have less healthy food intake in all age groups.

Plasma Inflammatory Biomarkers and Anorexia of Ageing among Community-Dwelling Older Adults: An Exploratory Analysis of the MAPT Study.

Anorexia of aging and biological aging might share physiological underpinnings. The aim of this secondary analysis was to investigate the associations between circulating inflammation-related markers and anorexia of aging in community-dwelling older adults. C-reactive protein (CRP), tumor necrosis factor receptor-1 (TNFR-1), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and growth/differentiation factor-15 (GDF-15) were measured in plasma. Anorexia of aging was defined by the response "severe/moderate decrease in food intake" to the first item of the Mini-Nutritional Assessment. We included 463 subjects (median age=74y, IQR=71-78; 63.1% women). 33 subjects (7.1%) presented with anorexia at baseline, whereas 25 out of 363 (6.9%) developed it along 1-year follow-up. We found that TNFR1 (OR=1.74, 95%CI=1.27-2.39) and GDF-15 (OR=1.38, 95%CI=1.01-1.89) were associated with a significant increase in the odds of presenting with anorexia of aging cross-sectionally. No further significant associations were found. Biological aging mechanisms might be involved in the pathogenesis of anorexia of aging.

Assessment and Management of Appetite Loss in Older Adults: An ICFSR Task Force Report.

The Appetite loss in older people is an important unmet clinical need in geriatrics. The International Conference on Frailty and Sarcopenia Research (ICFSR) organized a Task Force on April 20th 2022, in Boston, to discuss issues related to appetite loss in older people, in particular, the assessment tools currently available, its evaluation in the primary care setting, and considerations about its management. There is a high heterogeneity in terms of the etiology of appetite loss in older people and a gold standard assessment tool for evaluating this condition is still absent. Although this may render difficult the management of poor appetite in clinical practice, validated assessment tools are currently available to facilitate early identification of appetite loss and support care decisions. As research on biomarkers of appetite loss progresses, assessment tools will soon be used jointly with biomarkers for more accurate diagnosis and prognosis. In addition, efforts to foster the development of drugs with a favorable risk/benefit ratio to combat poor appetite should be strengthened.

Reliability of Self-Screening for Intrinsic Capacity Impairments Using the ICOPE Monitor App.

AIM: To verify the inter-rater agreement of the Integrated Care for Older People (ICOPE) STEP 1 screening tool using the ICOPE Monitor app, comparing self-assessment to a screening performed by a health professional. METHODS: We compared the results of the ICOPE Step 1 obtained by self-screening with those obtained by a professional screening using Gwet's agreement coefficient in two studies. Study 1 tested inter-rater reliability in participants to the INSPIRE-T cohort who agreed to undergo the self-and the professional screening on the same day. Study 2 used data from the INSPIRE-ICOPE care cohort. We included real-life users of the French health system whose first ICOPE Step 1 was a self-assessment followed by a professional Step 1within 130 days (mean=76 days, SD=60). RESULTS: Study 1 included 79 participants (45 aged less than 60, 34 aged 60 and over, 60% female, mean (SD) age of 54.5 (18.5) years). Of the 207 participants in Study 2, 49 were less than 60, and 158 were 60 and over (54% female, mean (SD) age 67 (16.1) years). Agreement coefficients in Study 1 ranged from 0.49 (CI95% 0.24; 0.66) in the cognition domain - moderate agreement) to 0.99 (CI95% 0.96;1.00) in the nutrition domain - very good agreement); and in Study 2 from 0.36 (CI95% 0.23;0.49) in the cognition domain to 0.97 (95% 0.95;1.00) in the nutrition domain. The agreement coefficients for the cognition and hearing domains were higher for the participants aged <60 than those aged 60 and over. The time orientation items (cognition) showed high reliability. CONCLUSION: Our study supports using ICOPE Step 1 as a self-assessment screening tool. High reliability was found for intrinsic capacity's nutrition, psychological, and locomotion domains, regardless of age. We discuss aspects of the self-assessment of cognition, vision, and hearing domains when using the ICOPE monitor app in older adults.

Effect of a 1-Year Nutritional Blend Supplementation on Plasma p-tau181 and GFAP Levels among Community-Dwelling Older Adults: A Secondary Analysis of the Nolan Trial.

Background: Observational studies and some randomized controlled trials have suggested that nutritional supplementation could be a possible intervention pathway to prevent cognitive decline and Alzheimer's disease (AD). As measuring amyloid-ß and tau pathophysiology by positron emission tomography (PET) or cerebrospinal fluid (CSF) analyses may be perceived as complex, plasma versions of such biomarkers have emerged as more accessible alternatives with comparable capacity of predicting cognitive impairment. Objectives: This study aimed to evaluate the effect of a 1-year intervention with a nutritional blend on plasma p-tau181 and glial fibrillary acidic protein (GFAP) levels in community-dwelling older adults. Effects were further assessed in exploratory analyses within sub-cohorts stratified according to p-tau status (with the third tertile considered as high: ≥15.1 pg/ mL) and to apolipoprotein E (APOE) ε4 allele status. Methods: A total of 289 participants ≥70 years (56.4% female, mean age 78.1 years, SD=4.7) of the randomized, double-blind, multicenter, placebo-controlled Nolan trial had their plasma p-tau181 assessed, and daily took either a nutritional blend (composed of thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid, cobalamin, vitamin E, vitamin C, vitamin D, choline, selenium, citrulline, eicosapentaenoic acid - EPA, and docosahexaenoic acid - DHA) or placebo for 1 year. Results: After 1-year, both groups presented a significant increase in plasma p-tau181 and GFAP values, with no effect of the intervention (p-tau181 between-group difference: 0.27pg/mL, 95%CI: -0.95, 1.48; p=0.665; GFAP between-group difference: -3.28 pg/mL, 95%CI: -17.25, 10.69; p=0.644). P-tau-and APOE ε4-stratified analyses provided similar findings. Conclusions: In community-dwelling older adults, we observed an increase in plasma p-tau181 and GFAP levels that was not different between the supplementation groups after one year.

Appetite Loss and Anorexia of Aging in Clinical Care: An ICFSR Task Force Report.

Appetite loss/anorexia of aging is a highly prevalent and burdensome geriatric syndrome that strongly impairs the quality of life of older adults. Loss of appetite is associated with several clinical conditions, including comorbidities and other geriatric syndromes, such as frailty. Despite its importance, appetite loss has been under-evaluated and, consequently, under-diagnosed and under-treated in routine clinical care. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met virtually on September 27th 2021 to debate issues related to appetite loss/anorexia of aging. In particular, topics related to the implementation and management of appetite loss in at-risk older adult populations, energy balance during aging, and the design of future clinical trials on this topic were discussed. Future actions in this field should focus on the systematic assessment of appetite in the care pathway of older people, such as the Integrated Care for Older People (ICOPE) program recommended by the World Health Organization. Moreover, clinical care should move from the assessment to the treatment of appetite loss/anorexia. Researchers continue to pursue their efforts to find out effective pharmacologic and non-pharmacologic interventions with a favorable risk/benefit ratio.

Omega-3 Supplementation for the Prevention of Cognitive Decline in Older Adults: Does It Depend on Homocysteine Levels?

BACKGROUND: Recent evidence point towards an interaction between omega-3 (n-3) polyunsaturated fatty acids (PUFA) and plasma homocysteine (Hcy). OBJECTIVES: This study tested the hypothesis that effects of red blood cell n-3 PUFA are modified according to baseline plasma Hcy in the large Mulit-domain Alzheimer Prevention Trial (MAPT) throughout the 3-years of treatment with an additional 2 years of observational follow-up. DESIGN: Experimental study. PARTICIPANTS: From the 1680 participants that were randomized in the four groups of the MAPT study (two of which received n-3 PUFA, the other two without n-3 PUFA), 782 were selected because they had baseline data on both Hcy and n-3 PUFA. MEASUREMENTS: Cognitive performance was measured with a broad set of cognitive tests including free and total recall of the cued selective reminding test, digit symbol substitution test, category naming test and Trail-making tests (TMT-A and B) and Clinical dementia rating scale. RESULTS: We found a significant association between TMT-A and red blood cell n-3 PUFA levels in participants with Hcy values ≤16.8 µMol/L after adjustments at baseline (Estimate: -1.3, 95% CI: -2.3; -0.3, p=0.01). Additionally, participants with high Hcy values had a significant worsening after adjustments in TMT-B after a 5-year n-3 PUFA supplementation, compared to low levels of Hcy (Mean difference: 34.8, 95% CI: 7.8;61.7). CONCLUSION: This study shows that Hcy levels could modify the association between red blood cell n-3 PUFA and executive function. People with high Hcy may benefit less from a n-3 PUFA supplementation to prevent cognitive decline.

Apelin controls emotional behavior in age- and metabolic state-dependent manner.

Apelin is a small peptide secreted by the adipose tissue notably in conditions of obesity-induced hyper-insulinemia. Apelin exerts a range of physiological functions at the periphery including the improvement of insulin sensitivity and the increase of muscle strength or cardiac contractibility. Interestingly, the brain is endowed with a high density of APJ, the single target of apelin, and growing evidence suggests various central actions of this adipokine. Recent studies reported that the intracerebroventricular infusion of apelin modulates emotional states in middle age stressed animals. However, results are so far been mixed and have not allowed for definitive conclusions about the impact of apelin on anxio-depressive-like phenotype. This study aims 1) to evaluate whether serum apelin levels are associated with mood in older adults and 2) to determine the impact of the genetic apelin inactivation in 12-month old mice fed a standard diet (STD) or in 6-month old mice fed a high fat diet (HFD). A higher plasma apelin level was associated with higher depressive symptoms in older adults. In line with these clinical findings, 12-month old apelin knock-out (Ap-/-) mice displayed a spontaneous antidepressant-like phenotype. In a marked contrast, 6-month old Ap-/- mice harbored a higher degree of peripheral insulin resistance than wild-types in response to HFD and were more prone to develop anxiety while the depressive-like state was not modified. We also provided evidence that such anxious behavior was associated with an impairment of central serotonergic and dopaminergic neuronal activities. Finally, although the insulin sensitizing drug metformin failed to reverse HFD-induced insulin resistance in 6-month old Ap-/- mice, it reversed their anxious phenotype. These results emphasize a complex contribution of apelin in the regulation of emotional state that might depend on the age and the metabolic status of the animals. Further investigations are warranted to highlight the therapeutic potential of manipulating the apelinergic system in mood-related disorders.

Biomarkers of Age-Related Frailty and Frailty Related to Diseases: An Exploratory, Cross-Sectional Analysis from the MAPT Study.

BACKGROUND: Frailty may in most cases result from two main causes: the aging process (age-related frailty) and diseases (evolving chronic conditions or acute medical illnesses - disease-related frailty). The biological determinants characterizing these two main causes of frailty may be different. OBJECTIVES: The aim of this study is to compare the biological and neuroimaging profile of people without frailty, those with age-related frailty, and subjects with disease-related frailty in community-dwelling older adults. MATERIAL AND METHODS: We performed a secondary, cross-sectional analysis from the Multidomain Alzheimer Preventive Trial (MAPT). We included 1199 subjects without frailty throughout the 5-year follow-up, 82 subjects with incident age-related frailty, and 53 with incident disease-related frailty. Available blood biomarkers involved nutritional (eg, vitamin D, omega-3 fatty acids), inflammatory-related (IL-6, TNFR1, GDF15), neurodegenerative (eg, beta-amyloid, neurofilament light chain) and neuroimaging markers (MRI, Amyloid-PET). RESULTS: Although not statistically significant, the results of the unadjusted model showed increasing gradients for inflammatory markers (GDF15, TNFR1) and decreasing gradients for nutritional and neuroimaging markers (omega 3 index, hippocampal volume) from age-related frailty participants to individuals with disease-related frailty. Considering the linear models we observed higher GDF15 values in disease-related frailty group compared to age-related frailty individuals [ß = 242.8 (49.5, 436.2)]. We did not find any significant difference between subjects without frailty and those with age-related frailty. Subjects with disease-related frailty compared to subjects without frailty had lower values of DHA [ß = -2.42 (-4.76, -0.08)], Omega 3 Index [ß = -0.50 (-0.95, -0.06)] and hippocampal volume [ß = -0.22 (-0.42,-0.02)]. They also had higher values of GDF15 [ß = 246.1 (88.9, 403.4)] and TNFR1 [ß = 157.5 (7.8, 307.2)]. CONCLUSION: Age-related frailty and disease-related frailty may represent different degrees of frailty severity on a biological level. Further research is needed to identify biomarkers potentially able to distinguish these classifications of frailty.

Circulating Levels of Apelin, GDF-15 and Sarcopenia: Lack of Association in the MAPT Study.

OBJECTIVES: Apelin and GDF-15 have been proposed as biomarkers of age-related sarcopenia but evidence in human models is scarce. This study aimed to explore the associations between blood apelin and GDF-15 with sarcopenia incidence and the evolution of sarcopenia components over two years in older adults >70 years. DESIGN: Secondary longitudinal analysis of the Multidomain Alzheimer Preventive Trial. PARTICIPANTS: Older adults (>70 years) attending primary care centers in France and Monaco. SETTING: Community. MEASUREMENTS: Serum Apelin (pg/mL) and plasma GDF-15 (pg/mL) were measured. Outcomes included sarcopenia defined by the European Working Group on Sarcopenia in Older People (EWGSOP) and its determinants (appendicular lean mass [ALM] evaluated through a Dual-energy X-ray Absorptiometry (DXA) scan, handgrip strength (HGS) and the 4-meter gait speed) measured over 2 years. Linear mixed models and logistic regression were used to explore the longitudinal associations. RESULTS: We included 168 subjects from MAPT (median age=76y, IQR=73-79; 78% women). Serum apelin was not significantly associated with sarcopenia incidence (OR=1.001;95%CI=1.000,1.001;p-value>0.05 in full-adjusted models) nor with ALM (ß=-5.8E-05;95%CI=-1.0E-04,2.12E-04;p>0.05), HGS (ß=-1.1E-04;95%CI=-5.0E-04,2.8E-04;p>0.05), and GS (ß=-5.1E-06;95%CI=-1.0E-05,2.0E-05;p>0.05) in fully adjusted models. Similarly, plasma GDF-15 was not associated with both the incidence of sarcopenia (OR=1.001,95%CI=1.000,1.002,p>0.05) and the evolution of its determinants ([ALM, ß=2.1E-05;95%CI=-2.6E-04,3.03E-04;p>0.05], HGS [ß=-5.9E-04;95%CI=-1.26E-03,8.1E-05; p>0.05] nor GS [ß=-2.6E-06;95%CI=-3.0E-05, 2.3E-05;p>0.05]) in fully adjusted models. CONCLUSIONS: Blood apelin and GDF-15 were not associated with sarcopenia incidence or with the evolution of sarcopenia components over a 2-year follow-up in community-dwelling older adults. Well-powered longitudinal studies are needed to confirm or refute our findings.

Trajectories of Symptoms in Nursing Home Residents after a Transfer to the Emergency Department.

OBJECTIVE: To describe the trajectories of pain, dyspnea, fever, confusion, agitation and fatigue of nursing home residents' (NHRs) after a transfer to the emergency department (ED). DESIGN: Observational multicenter study. SETTING: 17 EDs in France. PARTICIPANTS: 751 NHRs presenting to EDs over four non-consecutive weeks (one week per season) in 2016. MEASUREMENTS: Trajectories of symptoms (binary variables) including pain, dyspnea, fever, agitation, confusion and fatigue at four times: before ED transfer, during the transfer, in the ED and after discharge. RESULTS: Group-based multi-trajectory modelling was performed to identify groups of NHRs following similar trajectories of symptoms evolution after a transfer to ED. Five groups were identified. In group 1 (n=190), NHRs presented with confusion and a rising prevalence of fatigue. In group 2 (n=212), NHRs presented with a highly prevalent but declining pain. In group 3 (n=158), NHRs presented with similar peaking pain prevalence, rising confusion and fatigue, and a high but stable agitation prevalence. In group 4 (n=144), NHRs presented with a highly prevalent but declining dyspnea, rising then declining fever, rising confusion, and a high and fluctuating fatigue prevalence. In group 5 (n=47), NHRs presented with a highly prevalent but declining fever, rising then declining dyspnea, stable and high both fatigue and pain prevalence, stable and low prevalence of confusion. CONCLUSION: Symptom alleviation in NHRs transferred to ED was better achieved in those with pain, fever or dyspnea rather than in those with confusion, agitation and fatigue. NHRs' resilience through the stress of an ED transfer could be predicted by comorbidity and functional abilities, challenged by acute conditions representing various levels of stress intensity, and evaluated on the course of non-specific symptoms. NHRs' resilience is key to estimate the appropriateness of an ED transfer and should facilitate advance care planning regarding NHRs' hospitalizations.

Prospective Associations between Plasma Amyloid-Beta 42/40 and Frailty in Community-Dwelling Older Adults.

BACKGROUND: Brain amyloid-beta (Aß) plaques, a hallmark of the pathophysiology of Alzheimer's disease, have been associated with frailty. Whether the plasma Aß markers show similar relationship with frailty is unknown. OBJECTIVES: To investigate the prospective associations between plasma Aß42/40 ratio and overtime frailty in community-dwelling older adults. METHODS: From the 5-year Multidomain Alzheimer Preventive Trial (MAPT), we included 477 adults ≥70 years with available data on plasma Aß42/40 ratio (lower is worse). Fried frailty phenotype (robust, pre-frail and frail) was assessed at the same time-point of plasma Aß measures and after until the end of follow-up. The outcomes of interest were the change in the frailty phenotype over time (examined by mixed-effect ordinal logistic regressions) and incident frailty (examined by Cox proportional hazard models). RESULTS: Plasma Aß42/40 did not show significant associations with incident frailty; however, after adjusting for Apolipoprotein E (APOE) ε4 genotype, people in the lower quartile of plasma Aß42/40 (≤0.103) had higher risk of incident frailty (HR=2.63; 95% CI, 1.00 to 6.89), compared to those in the upper quartile (>0.123). Exploratory analysis found a significant association between the lower quartile of plasma Aß42/40 and incident frailty among APOE ε4 non-carriers (HR=3.48; 95% CI, 1.19 to 10.16), but not among carriers. No associations between plasma Aß42/40 and evolution of frailty were observed. CONCLUSION: No significant associations between plasma Aß42/40 and frailty were found when APOE ε4 status was not accounted into the model. Nevertheless, APOE ε4 non-carriers with high Aß burden might be more susceptible to develop frailty.

Frailty Index, Hospital Admission and Number of Days Spent in Hospital in Nursing Home Residents: Results from the Incur Study.

OBJECTIVES: To investigate the predictive capacity of an age-related deficit accumulation index (the so-called Frailty Index [FI] proposed by Rockwood) for hospital admission (HA) and number of days spent in hospital (DSH) among nursing home residents. DESIGN, SETTING AND PARTICIPANTS: Data are from a longitudinal cohort study, the Incidence of pNeumonia and related ConseqUences in nursing home Residents (INCUR), of 768 elder people (75.4% women) living in 13 nursing homes in France. MEASUREMENTS: The FI was computed taking into account 30 possible deficits at the baseline visit. Hospital admissions were defined as all urgent and involuntary admissions including unplanned readmissions. The length of stay was the total number of days spent by the resident in the hospital. Cox proportional hazard models in the presence of competing risks (death) were performed to study the relationship between the FI and HA over a 12-month follow-up. A Zero-inflated negative binomial regression was performed to study the association between the FI and DSH. RESULTS: Mean age of participants was 86.7 (standard deviation [SD] 6.9) years, with a mean FI of 0.37 (SD 0.11). At the end of the follow-up, 238 (30.9%) HA events were recorded. Positive associations of the FI with DSH and HA were reported (per 0.01 FI increment: age- and gender-adjusted hazard ratio 1.15, 95% confidence interval 1.020-1.297, p=0.02 and OR 1.209 (1.075 - 1.359, p<0.001, respectively). CONCLUSIONS AND IMPLICATIONS: The FI is a strong predictor of negative health-related outcomes as HA and DSH events, even with very old and complex nursing home residents.

A Web-Based Multidomain Lifestyle Intervention for Older Adults: The eMIND Randomized Controlled Trial.

Importance/Objective: To describe the feasibility and acceptability of a 6-month web-based multidomain lifestyle training intervention for community-dwelling older people and to test the effects of the intervention on both function- and lifestyle-related outcomes. DESIGN: 6-month, parallel-group, randomized controlled trial (RCT). SETTING: Toulouse area, South-West, France. PARTICIPANTS: Community-dwelling men and women, ≥ 65 years-old, presenting subjective memory complaint, without dementia. INTERVENTION: The web-based multidomain intervention group (MIG) received a tablet to access the multidomain platform and a wrist-worn accelerometer measuring step counts; the control group (CG) received only the wrist-worn accelerometer. The multidomain platform was composed of nutritional advices, personalized exercise training, and cognitive training. Main outcomes and measures: Feasibility, defined as the proportion of people connecting to ≥75% of the prescribed sessions, and acceptability, investigated through content analysis from recorded semi-structured interviews. Secondary outcomes included clinical (eg, cognitive function, mobility, health-related quality of life (HRQOL)) and lifestyle (eg, step count, food intake) measurements. RESULTS: Among the 120 subjects (74.2 ±5.6 years-old; 57.5% women), 109 completed the study (n=54, MIG; n=55, CG). 58 MIG subjects connected to the multidomain platform at least once; among them, adherers of ≥75% of sessions varied across multidomain components: 37 people (63.8% of 58 participants) for cognitive training, 35 (60.3%) for nutrition, and three (5.2%) for exercise; these three persons adhered to all multidomain components. Participants considered study procedures and multidomain content in a positive way; the most cited weaknesses were related to exercise: too easy, repetitive, and slow progression. Compared to controls, the intervention had a positive effect on HRQOL; no significant effects were observed across the other clinical and lifestyle outcomes. CONCLUSIONS AND RELEVANCE: Providing multidomain lifestyle training through a web-platform is feasible and well-accepted, but the training should be challenging enough and adequately progress according to participants' capabilities to increase adherence. Recommendations for a larger on-line multidomain lifestyle training RCT are provided.

Frequency of Conditions Associated with Declines in Intrinsic Capacity According to a Screening Tool in the Context of Integrated Care for Older People.

BACKGROUND: The screening tool of the Integrated Care for Older People (ICOPE Step 1), designed to detect declines in the domains of intrinsic capacity, has been incipiently investigated in older adult populations. OBJECTIVES: To retrospectively estimate the frequency of priority conditions associated with declines in intrinsic capacity according to an adaptation of the screening tool ICOPE Step 1 among participants of the Multidomain Alzheimer Preventive Trial (MAPT). DESIGN: A cross-sectional retrospective analysis from the baseline assessment of the MAPT. SETTING: The data was gathered during a preventive consultation for cardiovascular risk factors in memory clinics in France. PARTICIPANTS: Seven hundred fifty-nine older adults aged 70-89 years with memory complaints, allocated to the multidomain groups of the MAPT study. MEASUREMENTS: Five domains of intrinsic capacity (cognition, locomotion, nutrition, sensorial, and psychological) were assessed using a screening tool similar to the ICOPE Step 1 (MAPT Step 1). The frequency of six conditions associated with declines in intrinsic capacity (cognitive decline, limited mobility, malnutrition, visual impairment, hearing loss, and depressive symptoms) was obtained for older adults with memory complaints participating in the MAPT study. RESULTS: Overall, 89.3% of the participants had one or more conditions associated with declines in intrinsic capacity. The overall frequency of each condition was: 52.2% for cognitive decline, 20.2% for limited mobility, 6.6% for malnutrition, 18.1% for visual impairment, 56.2% for hearing loss, and 39% for depressive symptoms. CONCLUSION: After being screened with an adaptation of the ICOPE step 1 (MAPT step 1) tool, 9/10 older adults had one or more conditions associated with declines in intrinsic capacity. The relative frequency differs across conditions and could probably be lower in a population without memory complaints. The frequency of screened conditions associated with declines in IC highlights how relevant it is to develop function-centered care modalities to promote healthy aging.

The INSPIRE Research Initiative: A Program for GeroScience and Healthy Aging Research Going from Animal Models to Humans and the Healthcare System.

Aging is the most important risk factor for the onset of several chronic diseases and functional decline. Understanding the interplays between biological aging and the biology of diseases and functional loss as well as integrating a function-centered approach to the care pathway of older adults are crucial steps towards the elaboration of preventive strategies (both pharmacological and non-pharmacological) against the onset and severity of burdensome chronic conditions during aging. In order to tackle these two crucial challenges, ie, how both the manipulation of biological aging and the implementation of a function-centered care pathway (the Integrated Care for Older People (ICOPE) model of the World Health Organization) may contribute to the trajectories of healthy aging, a new initiative on Gerosciences was built: the INSPIRE research program. The present article describes the scientific background on which the foundations of the INSPIRE program have been constructed and provides the general lines of this initiative that involves researchers from basic and translational science, clinical gerontology, geriatrics and primary care, and public health.

The INSPIRE Bio-Resource Research Platform for Healthy Aging and Geroscience: Focus on the Human Translational Research Cohort (The INSPIRE-T Cohort).

BACKGROUND: The Geroscience field focuses on the core biological mechanisms of aging, which are involved in the onset of age-related diseases, as well as declines in intrinsic capacity (IC) (body functions) leading to dependency. A better understanding on how to measure the true age of an individual or biological aging is an essential step that may lead to the definition of putative markers capable of predicting healthy aging. OBJECTIVES: The main objective of the INStitute for Prevention healthy agIng and medicine Rejuvenative (INSPIRE) Platform initiative is to build a program for Geroscience and healthy aging research going from animal models to humans and the health care system. The specific aim of the INSPIRE human translational cohort (INSPIRE-T cohort) is to gather clinical, digital and imaging data, and perform relevant and extensive biobanking to allow basic and translational research on humans. METHODS: The INSPIRE-T cohort consists in a population study comprising 1000 individuals in Toulouse and surrounding areas (France) of different ages (20 years or over - no upper limit for age) and functional capacity levels (from robustness to frailty, and even dependency) with follow-up over 10 years. Diversified data are collected annually in research facilities or at home according to standardized procedures. Between two annual visits, IC domains are monitored every 4-month by using the ICOPE Monitor app developed in collaboration with WHO. Once IC decline is confirmed, participants will have a clinical assessment and blood sampling to investigate markers of aging at the time IC declines are detected. Biospecimens include blood, urine, saliva, and dental plaque that are collected from all subjects at baseline and then, annually. Nasopharyngeal swabs and cutaneous surface samples are collected in a large subgroup of subjects every two years. Feces, hair bulb and skin biopsy are collected optionally at the baseline visit and will be performed again during the longitudinal follow up. EXPECTED RESULTS: Recruitment started on October 2019 and is expected to last for two years. Bio-resources collected and explored in the INSPIRE-T cohort will be available for academic and industry partners aiming to identify robust (set of) markers of aging, age-related diseases and IC evolution that could be pharmacologically or non-pharmacologically targetable. The INSPIRE-T will also aim to develop an integrative approach to explore the use of innovative technologies and a new, function and person-centered health care pathway that will promote a healthy aging.