Cost of care pathways before and after appropriate and inappropriate transfers to the emergency department among nursing home residents: results from the FINE study.

BACKGROUND: Transfers of nursing home (NH) residents to the emergency department (ED) is frequent. Our main objective was to assess the cost of care pathways 6 months before and after the transfer to the emergency department among NH residents, according to the type of transfer (i.e. appropriate or inappropriate). METHODS: This was a part of an observational, multicenter, case-control study: the Factors associated with INappropriate transfer to the Emergency department among nursing home residents (FINE) study. Sixteen public hospitals of the former Midi-Pyrénées region participated in recruitment, in 2016. During the inclusion period, all NH residents arriving at the ED were included. A pluri-disciplinary team categorized each transfer to the ED into 2 groups: appropriate or inappropriate. Direct medical and nonmedical costs were assessed from the French Health Insurance (FHI) perspective. Healthcare resources were retrospectively gathered from the FHI database and valued using the tariffs reimbursed by the FHI. Costs were recorded over a 6-month period before and after transfer to the ED. Other variables were used for analysis: sex, age, Charlson score, season, death and presence inside the NH of a coordinating physician or a geriatric nursing assistant. RESULTS: Among the 1037 patients initially included in the FINE study, 616 who were listed in the FHI database were included in this economic study. Among them, 132 (21.4%) had an inappropriate transfer to the ED. In the 6 months before ED transfer, total direct costs on average amounted to 8,145€ vs. 6,493€ in the inappropriate and appropriate transfer groups, respectively. In the 6 months after ED transfer, they amounted on average to 9,050€ vs. 12,094€. CONCLUSIONS: Total costs on average are higher after transfer to the ED, but there is no significant increase in healthcare expenditure with inappropriate ED transfer. Support for NH staff and better pathways of care could be necessary to reduce healthcare expenditures in NH residents. TRIAL REGISTRATION: clinicaltrials.gov, NCT02677272.

Motoric cognitive risk syndrome and incident dementia: results from a population-based prospective and observational cohort study.

BACKGROUND AND PURPOSE: Motoric cognitive risk syndrome (MCR), which is the juncture of subjective cognitive complaint and slow gait speed, is a pre-dementia stage. The aims of the study are (i) to compare characteristics between individuals who have MCR defined using slow walking speed and/or increased five-times-sit-to-stand (FTSS) time as its motor component(s); and (ii) to characterize the association of MCR and its various motor components with incident dementia including Alzheimer disease and non-Alzheimer dementia in the participants of the Epidémiologie de l'Ostéoporose (EPIDOS) study. METHODS: This prospective and observational cohort study selected 651 participants recruited from the EPIDOS study in Toulouse (France). MCR was defined as the association of subjective cognitive complaint and slow gait speed and/or increased FTSS time in participants without either dementia and mobility disabilities at baseline. Individuals with dementia were prospectively diagnosed during the physical and neuropsychological assessments included in the 7-year follow-up. RESULTS: The prevalence of MCR was around 7% when using an exclusive motor criterion, either slow gait speed or increased FTSS time, and was 20.9% when MCR subgroups were pooled. MCR was positively associated with incident dementia regardless of its type, and with Alzheimer disease in the slow gait speed MCR subgroup [odds ratio (OR) > 2.18 with P ≤ 0.037] but not with non-Alzheimer dementia. No significant association between incident dementia and MCR defined using increased FTSS time was shown. CONCLUSIONS: Our findings confirm that MCR is associated with incident dementia and that slow gait speed is the appropriate motor criterion for detecting dementia risk.

Motoric cognitive risk syndrome and mortality: results from the EPIDOS cohort.

BACKGROUND AND PURPOSE: Cognitive impairment, slow walking speed and motoric cognitive risk syndrome (MCR) have separately been associated with an increased risk for mortality in the short term. The aim of the study was to examine the association of MCR and its components [i.e. subjective cognitive complaint (SCC) and slow walking speed] with short-, medium- and long-term mortality in older community-dwellers. METHODS: In all, 3778 participants from the Epidémiologie de l'Ostéoporose (EPIDOS) study were selected. MCR was defined as the combination of slow walking speed and SCC in participants without major neurocognitive disorders. Deaths were prospectively recorded using mail, phone calls, questionnaires and/or the French national death registry at 5, 10, 15 and 19 (end of follow-up period) years. RESULTS: Over the follow-up of 19 years, 80.5% (n = 3043) participants died. Slow walking speed and MCR were associated with mortality [hazard ratio (HR) 1.20 with P = 0.004 for slow walking speed and HR = 1.26 with P = 0.002 for MCR at 10 years; HR = 1.27 with P ≤ 0.001 for slow walking speed and HR = 1.22 with P = 0.001 for MCR at 15 years; HR = 1.41 with P ≤ 0.001 at 19 years for slow walking speed and MCR]. There was no association between SCC and mortality. Kaplan-Meier distributions of mortality showed that participants with MCR and slow walking speed died earlier compared to healthy participants and those with SCC (P < 0.001). CONCLUSIONS: Slow walking speed and MCR were associated with an increased risk for mortality at the medium and long term, whereas no association was found with SCC.

Vitamin D deficiency is associated with orthostatic hypotension in oldest-old women.

OBJECTIVES: Orthostatic hypotension, a condition that mostly affects 'oldest-old' (i.e. ≥80 years) adults, is primarily explained by age-related dysfunction of blood pressure control. Vitamin D may contribute to blood pressure control. The aim of this study was to determine whether vitamin D deficiency is associated with orthostatic hypotension in oldest-old adults. DESIGN: Cross-sectional analysis at baseline of the EPIDOS study. SETTING: Five French areas. PARTICIPANTS: A total of 329 community-dwelling oldest-old women (mean age 83.3 ± 0.2 years). MAIN OUTCOMES MEASURES: Orthostatic hypotension was defined as a systolic blood pressure drop of ≥20 mmHg and/or a diastolic blood pressure drop of ≥10 mmHg within 3 min of standing. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25OHD) concentration ≤10 ng mL(-1) . Covariates included in the models were age, body mass index, diabetes mellitus, supine mean arterial pressure, number of drugs taken per day, use of antihypertensive or psychoactive drugs, cognition, quadriceps strength, current smoking, alcohol consumption, serum concentrations of parathyroid hormone, calcium and creatinine and season of testing. RESULTS: Diastolic orthostatic hypotension was observed more often among women with vitamin D deficiency (19.2%) compared to those without (10.0%; P = 0.03). There was an inverse linear association between 25OHD concentration and change in diastolic blood pressure after 3 min of standing (adjusted ß = -0.07, P = 0.046). Similarly, 25OHD deficiency was associated with orthostatic hypotension [adjusted odds ratio (OR) 3.36, P = 0.004], specifically with diastolic orthostatic hypotension (adjusted OR 3.81, P = 0.003). CONCLUSIONS: 25OHD deficiency was associated with orthostatic hypotension in oldest-old women, due to a greater drop in diastolic blood pressure on standing. This finding may lead to better understanding of the pathophysiology of falls in oldest-old adults with vitamin D deficiency.

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.

Nutrition for the older adult - Current concepts. Report from an ESPEN symposium.

BACKGROUND & AIMS: In view of the global demographic shift, a scientific symposium was organised by the European Society for Clinical Nutrition and Metabolism (ESPEN) to address nutrition-related challenges of the older population and provide an overview of the current state of knowledge. METHODS: Eighteen nutrition-related issues of the ageing global society were presented by international experts during the symposium and summarised in this report. RESULTS: Anorexia of ageing, dysphagia, malnutrition, frailty, sarcopenia, sarcopenic obesity, and the metabolic syndrome were highlighted as major nutrition-related geriatric syndromes. Great progress has been made in recent years through standardised definitions of some but not all syndromes. Regarding malnutrition, the GLIM approach has shown to be suitable also in older adults, justifying its continuous implementation. For anorexia of ageing, a consensus definition is still required. Intervention approaches should be integrated and person-centered with the aim of optimizing intrinsic capacity and maintaining functional capacity. Landmark studies like EFFORT and FINGER have impressively documented the potential of individualised and multifactorial interventions for functional and health benefits. Combining nutritional intervention with physical training seems particularly important whereas restrictive diets and drug treatment should generally be used with caution because of undesirable risks. Obesity management in older adults should take into account the risk of promoting sarcopenia. CONCLUSIONS: In the future, even more individualised approaches like precision nutrition may enable better nutritional care. Meanwhile all stakeholders should focus on a better implementation of currently available strategies and work closely together to improve nutritional care for older adults.

Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept.

PURPOSE: To evaluate the impact of dosimetry based on MAA SPECT/CT for the prediction of response, toxicity and survival, and for treatment planning in patients with hepatocellular carcinoma (HCC) treated with (90)Y-loaded glass microspheres (TheraSphere®). METHODS: TheraSphere® was administered to 71 patients with inoperable HCC. MAA SPECT/CT quantitative analysis was used for the calculation of the tumour dose (TD), healthy injected liver dose (HILD), and total injected liver dose. Response was evaluated at 3 months using EASL criteria. Time to progression (TTP) and overall survival (OS) were evaluated using the Kaplan-Meier method. Factors potentially associated with liver toxicity were combined to construct a liver toxicity score (LTS). RESULTS: The response rate was 78.8%. Median TD were 342 Gy for responding lesions and 191 Gy for nonresponding lesions (p < 0.001). With a threshold TD of 205 Gy, MAA SPECT/CT predicted response with a sensitivity of 100% and overall accuracy of 90%. Based on TD and HILD, 17 patients underwent treatment intensification resulting in a good response rate (76.4%), without increased grade III liver toxicity. The median TTP and OS were 5.5 months (2-9.5 months) and 11.5 months (2-31 months), respectively, in patients with TD <205 Gy and 13 months (10-16 months) and 23.2 months (17.5-28.5 months), respectively, in those with TD >205 Gy (p = 0.0015 and not significant). Among patients with portal vein thrombosis (PVT) (n = 33), the median TTP and OS were 4.5 months (2-7 months) and 5 months (2-8 months), respectively, in patients with TD <205 Gy and 10 months (6-15.2 months) and 21.5 months (12-28.5 months), respectively, in those with TD >205 Gy (p = 0.039 and 0.005). The median OS was 24.5 months (18-28.5 months) in PVT patients with TD >205 Gy and good PVT targeting on MAA SPECT/CT. The LTS was able to detect severe liver toxicity (n = 6) with a sensitivity of 83% and overall accuracy of 97%. CONCLUSION: Dosimetry based on MAA SPECT/CT was able to accurately predict response and survival in patients treated with glass microspheres. This method can be used to adapt the injected activity without increasing liver toxicity, thus defining a new concept of boosted selective internal radiation therapy (B-SIRT). This new concept and LTS enable fully personalized treatment planning with glass microspheres to be achieved.

Tools in the assessment of sarcopenia.

This review provides a framework for the development of an operational definition of sarcopenia and of the potential end points that might be adopted in clinical trials among older adults. While the clinical relevance of sarcopenia is widely recognized, there is currently no universally accepted definition of the disorder. The development of interventions to alter the natural history of sarcopenia also requires consensus on the most appropriate end points for determining outcomes of clinical importance which might be utilized in intervention studies. We review current approaches to the definition of sarcopenia and the methods used for the assessment of various aspects of physical function in older people. The potential end points of muscle mass, muscle strength, muscle power, and muscle fatigue, as well as the relationships between them, are explored with reference to the availability and practicality of the available methods for measuring these end points in clinical trials. Based on current evidence, none of the four potential outcomes in question is sufficiently comprehensive to recommend as a uniform single outcome in randomized clinical trials. We propose that sarcopenia may be optimally defined (for the purposes of clinical trial inclusion criteria as well as epidemiological studies) using a combination of measures of muscle mass and physical performance. The choice of outcome measures for clinical trials in sarcopenia is more difficult; co-primary outcomes, tailored to the specific intervention in question, may be the best way forward in this difficult but clinically important area.

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.

Frailty and sarcopenia: definitions and outcome parameters.

An operational definition of musculoskeletal decline in older people is needed to allow development of interventions for prevention or treatment, as was developed for the treatment of osteoporosis. Frailty and sarcopenia are linked, but distinct, correlates of musculoskeletal aging that have many causes, including age-related changes in body composition, inflammation, and hormonal imbalance. With the emergence of a number of exciting candidate therapies to retard the loss of muscle mass with aging, the derivation of a consensual definition of sarcopenia and physical frailty becomes an urgent priority. Although several consensual definitions have been proposed, these require clinical validation. An operational definition, which might provide a threshold for treatment/trial inclusion, should incorporate a loss of muscle mass as well as evidence of a decrease in muscle strength and/or physical activity. Evidence is required for a link between improvements in the measures of muscle strength and/or physical activity and clinical outcomes to allow development of interventions to improve clinical outcomes in frail older patients.

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.

Challenges in the Development of Drugs for Sarcopenia and Frailty - Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force.

Sarcopenia and frailty represent two burdensome conditions, contributing to a broad spectrum of adverse outcomes. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met virtually in September 2021 to discuss the challenges in the development of drugs for sarcopenia and frailty. Lifestyle interventions are the current mainstay of treatment options in the prevention and management of both conditions. However, pharmacological agents are needed for people who do not respond to lifestyle modifications, for those who are unable to adhere, or for whom such interventions are inaccessible/unfeasible. Preliminary results of ongoing trials were presented and discussed. Several pharmacological candidates are currently under clinical evaluation with promising early results, but none have been approved for either frailty or sarcopenia. The COVID-19 pandemic has reshaped how clinical trials are conducted, in particular by enhancing the usefulness of remote technologies and assessments/interventions.

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.

Resilience: Biological Basis and Clinical Significance - A Perspective Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force.

The Resilience is a construct receiving growing attention from the scientific community in geriatrics and gerontology. Older adults show extremely heterogeneous (and often unpredictable) responses to stressors. Such heterogeneity can (at least partly) be explained by differences in resilience (i.e., the capacity of the organism to cope with stressors). The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met in Boston (MA,USA) on April 20, 2022 to discuss the biological and clinical significance of resilience in older adults. The identification of persons with low resilience and the prompt intervention in this at-risk population may be critical to develop and implement preventive strategies against adverse events. Unfortunately, to date, it is still challenging to capture resilience, especially due to its dynamic nature encompassing biological, clinical, subjective, and socioeconomic factors. Opportunities to dynamically measure resilience were discussed during the ICFSR Task Force meeting, emphasizing potential biomarkers and areas of intervention. This article reports the results of the meeting and may serve to support future actions in the field.

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.

Serum vitamin D deficiency as a predictor of incident non-Alzheimer dementias: a 7-year longitudinal study.

BACKGROUND: Hypovitaminosis D has been cross-sectionally associated with dementia and stroke. The objective of this longitudinal study was to determine whether serum vitamin D deficiency at baseline could predict the onset of non-Alzheimer dementias (NAD) within 7 years among older women. METHODS: Forty high-functioning older women (78.4 years, 76.4/82.0; median, 25th/75th percentile) from the EPIDOS Toulouse study were divided into two groups based on vitamin D deficiency (i.e., serum 25-hydroxyvitamin D <10 ng/ml) at baseline. At the end of the 7-year follow-up period, women matching the DSM-IV but not the NINCDS-ADRDA criteria were diagnosed with NAD while those matching the NINCDS-ADRDA criteria were considered to have Alzheimer's disease (AD). Subtle cognitive impairments at baseline, cardiovascular risk factors and Parkinson's disease were used as potential confounders. RESULTS: NAD was reported in 6 women (82.8 years, 80.6/86.0) after 7 years of follow-up. More NAD were observed in women with vitamin D deficiency (p = 0.023). There was no between-group difference regarding the onset of AD (p = 0.332). We found an association between vitamin D deficiency at baseline and the onset of NAD (adjusted odds ratio = 19.57, p = 0.042). Conversely, vitamin D deficiency was not associated with AD (p = 0.222). CONCLUSION: Baseline vitamin D deficiency predicted the onset of NAD within 7 years among older women.