Sarcopenia and poor nutritional status in older adults.

BACKGROUND & AIMS: The association between sarcopenia and malnutrition has been poorly studied in the older population. The purpose of this study is to address the association between sarcopenia, according to different validated definitions, and nutritional status in a large population of community-dwelling older adults. METHODS: Observational, cross-sectional study of the Geriatric Frailty Clinic (GFC) for Assessment of Frailty and Prevention of Disability, held by the "Gérontopôle" of the Toulouse University Hospital. Patients aged above 65 years who benefitted from a Dual X-ray Densitometry (DXA) during their assessment at the GFC from June 5th 2013 to January 28th 2020 were included. Sarcopenia was defined according to proposed validated definitions. The Mini Nutritional Assessment (MNA) was used to stratify nutritional status, and identify patients with a poor nutritional status (at risk of malnutrition or malnourished, MNA <24). Multiple logistic regression analyses were performed between MNA and each sarcopenia definition adjusted for confounders. RESULTS: Among the 938 patients with DXA data, a total of 809 (86.2 %) subjects were included in the analysis (mean age 81.8 ± 6.9 years, 527 females (65.1 %)). Prevalence of sarcopenia ranged from 12.6 % to 44.9 %, according to various definitions. Overall 244 (30.2 %) of the patients had a poor nutritional status (MNA-score <24), Baumgartner and Newman definitions of sarcopenia were both associated with low MNA-scores (OR = 4.69, CI 3.15-6.98 and OR = 2.30, CI 1.55-3.14, respectively), EWGSOP2 "confirmed sarcopenia" definition was also associated with low MNA-scores (OR = 3.68, CI 2.30-5.89), as well as for the lean mass definition according EWGSOP2 cut-off (OR 5.22 CI 3.52-7.73). Both FNIH and EWGSOP2 "probable sarcopenia" definitions were not associated with the risk of malnutrition. CONCLUSIONS: In this study, the prevalence of sarcopenia ranged from 12.6 to 44.9 % according to various definitions. A score of MNA under 24, was associated with almost all of the sarcopenia definitions. This study reinforces the concept that malnutrition and sarcopenia are strictly related. When facing malnutrition in daily clinical practice, body composition should be assessed and the proposed nutritional intervention should be tailored by these results in order to prevent the onset of late-life disability.

Can We Use Blood Biomarkers as Entry Criteria and for Monitoring Drug Treatment Effects in Clinical Trials? A Report from the EU/US CTAD Task Force.

In randomized clinical trials (RCTs) for Alzheimer's Disease (AD), cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers are currently used for the detection and monitoring of AD pathological features. The use of less resource-intensive plasma biomarkers could decrease the burden to study volunteers and limit costs and time for study enrollment. Blood-based markers (BBMs) could thus play an important role in improving the design and the conduct of RCTs on AD. It remains to be determined if the data available on BBMs are strong enough to replace CSF and PET biomarkers as entry criteria and monitoring tools in RCTs.

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.

Blood Biomarkers from Research Use to Clinical Practice: What Must Be Done? A Report from the EU/US CTAD Task Force.

Timely and accurate diagnosis of Alzheimer's disease (AD) in clinical practice remains challenging. PET and CSF biomarkers are the most widely used biomarkers to aid diagnosis in clinical research but present limitations for clinical practice (i.e., cost, accessibility). Emerging blood-based markers have the potential to be accurate, cost-effective, and easily accessible for widespread clinical use, and could facilitate timely diagnosis. The EU/US CTAD Task Force met in May 2022 in a virtual meeting to discuss pathways to implementation of blood-based markers in clinical practice. Specifically, the CTAD Task Force assessed: the state-of-art for blood-based markers, the current use of blood-based markers in clinical trials, the potential use of blood-based markers in clinical practice, the current challenges with blood-based markers, and the next steps needed for broader adoption in clinical practice.

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.

Framework Implementation of the INSPIRE ICOPE-CARE Program in Collaboration with the World Health Organization (WHO) in the Occitania Region.

INTRODUCTION: Limiting the number of dependent older people in coming years will be a major economic and human challenge. In response, the World Health Organization (WHO) has developed the «Integrated Care for Older People (ICOPE)¼ approach. The aim of the ICOPE program is to enable as many people as possible to age in good health. To reach this objective, the WHO proposes to follow the trajectory of an individual's intrinsic capacity, which is the composite of all their physical and mental capacities and comprised of multiple domains including mobility, cognition, vitality / nutrition, psychological state, vision, hearing. OBJECTIVE: The main objective of the INSPIRE ICOPE-CARE program is to implement, in clinical practice at a large scale, the WHO ICOPE program in the Occitania region, in France, to promote healthy aging and maintain the autonomy of seniors using digital medicine. METHOD: The target population is independent seniors aged 60 years and over. To follow this population, the 6 domains of intrinsic capacity are systematically monitored with pre-established tools proposed by WHO especially STEP 1 which has been adapted in digital form to make remote and large-scale monitoring possible. Two tools were developed: the ICOPE MONITOR, an application, and the BOTFRAIL, a conversational robot. Both are connected to the Gerontopole frailty database. STEP 1 is performed every 4-6 months by professionals or seniors themselves. If a deterioration in one or more domains of intrinsic capacity is identified, an alert is generated by an algorithm which allows health professionals to quickly intervene. The operational implementation of the INSPIRE ICOPE-CARE program in Occitania is done by the network of Territorial Teams of Aging and Prevention of Dependency (ETVPD) which have more than 2,200 members composed of professionals in the medical, medico-social and social sectors. Targeted actions have started to deploy the use of STEP 1 by healthcare professionals (physicians, nurses, pharmacists,…) or different institutions like French National old age insurance fund (CNAV), complementary pension funds (CEDIP), Departmental Council of Haute Garonne, etc. Perspective: The INSPIRE ICOPE-CARE program draws significantly on numeric tools, e-health and digital medicine to facilitate communication and coordination between professionals and seniors. It seeks to screen and monitor 200,000 older people in Occitania region within 3 to 5 years and promote preventive actions. The French Presidential Plan Grand Age aims to largely implement the WHO ICOPE program in France following the experience of the INSPIRE ICOPE-CARE program in Occitania.

Age-Related Frailty: A Clinical Model for Geroscience?

In their everyday practice, geriatricians are confronted with the fact that older age and multimorbidity are associated to frailty. Indeed, if we take the example of a very old person with no diseases that progressively becomes frail with no other explanation, there is a natural temptation to link frailty to aging. On the other hand, when an old person with a medical history of diabetes, arthritis and congestive heart failure becomes frail there appears an obvious relationship between frailty and comorbidity. The unsolved question is: Considering that frailty is multifactorial and in the majority of cases comorbidity and aging are acting synergistically, can we disentangle the main contributor to the origin of frailty: disease or aging? We believe that it is important to be able to differentiate age-related frailty from frailty related to comorbidity. In fact, with the emergence of geroscience, the physiopathology, diagnosis, prognosis and treatment will probably have to be different in the future.

Can We Distinguish Age-Related Frailty from Frailty Related to Diseases ? Data from the MAPT Study.

BACKGROUND: No study has tried to distinguish subjects that become frail due to diseases (frailty related to diseases) or in the absence of specific medical events; in this latter case, it is possible that aging process would act as the main frailty driver (age-related frailty). OBJECTIVES: To classify subjects according to the origin of physical frailty: age-related frailty, frailty related to diseases, frailty of uncertain origin, and to compare their clinical characteristics. MATERIALS AND METHODS: We performed a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT), including 195 subjects ≥70 years non-frail at baseline who became frail during a 5-year follow-up (mean age 77.8 years ± 4.7; 70% female). Physical frailty was defined as presenting ≥3 of the 5 Fried criteria: weight loss, exhaustion, weakness, slowness, low physical activity. Clinical files were independently reviewed by two different clinicians using a standardized assessment method in order to classify subjects as: "age-related frailty", "frailty related to diseases" or "frailty of uncertain origin". Inconsistencies among the two raters and cases of uncertain frailty were further assessed by two other experienced clinicians. RESULTS: From the 195 included subjects, 82 (42%) were classified as age-related frailty, 53 (27%) as frailty related to diseases, and 60 (31%) as frailty of uncertain origin. Patients who became frail due to diseases did not differ from the others groups in terms of functional, cognitive, psychological status and age at baseline, however they presented a higher burden of comorbidity as measured by the Cumulative Illness Rating Scale (CIRS) (8.20 ± 2.69; vs 6.22 ± 2.02 frailty of uncertain origin; vs. 3.25 ± 1.65 age-related frailty). Time to incident frailty (23.4 months ± 12.1 vs. 39.2 ± 19.3 months) and time spent in a pre-frailty condition (17.1 ± 11.4 vs 26.6 ± 16.6 months) were shorter in the group of frailty related to diseases compared to age-related frailty. Orthopedic diseases (n=14, 26%) were the most common pathologies leading to frailty related to diseases, followed by cardiovascular diseases (n=9, 17%) and neurological diseases (n = 8, 15%). CONCLUSION: People classified as age-related frailty and frailty related to diseases presented different frailty-associated indicators. Future research should target the underlying biological cascades leading to these two frailty classifications, since they could ask for distinct strategies of prevention and management.

Predictive Factors of In-Hospital Mortality in Older Adults with Community-Acquired Bloodstream Infection.

OBJECTIVES: To assess the prevalence of intra-hospital mortality and associated risk factors in older people aged 75+, admitted with blood stream infections (BSI). DESIGN: Single center retrospective study performed in an 850-bed of the academic hospital of the Université Libre de Bruxelles. SETTING AND PARTICIPANTS: From January 2015 to December 2017, all inpatients over 75 years old admitted with BSI were included. MEASURES: Demographical, clinical and microbiological data were collected. RESULTS: 212 patients were included: median age was 82 [79-85] years and 60 % were female. The in-hospital mortality rate was 19%. The majority of microorganisms were Gram-negative strains, of which Escherichia coli was the most common, and urinary tract infection was the most common origin of BSI. Compared to patients who survived, the non-survivor group had a higher SOFA score (6 versus 3, p<0.0001), a higher comorbidity score (5 versus 4, p<0.0001), more respiratory tract infections (28 vs 6 %, p < 0.0001) and fungal infections (5 vs 1 %, p = 0.033), bedridden status (60 vs 25 %, p < 0.0001), and healthcare related infections (60 vs 40 %, p = 0.019). Using Cox multivariable regression analysis, only SOFA score was independently associated with mortality (HR 1.75 [95%IC 1.52-2.03], p<0.0001). CONCLUSIONS AND IMPLICATIONS: BSI in older people are severe infections associated with a significant in-hospital mortality. Severity of clinical presentation at onset remains the most important predictor of mortality for BSI in older people. BSI originating from respiratory source and bedridden patients are at greater risk of intra-hospital mortality. Further prospective studies are needed to confirm these results.