Validating intrinsic capacity to measure healthy aging in an upper middle-income country: Findings from the ELSI-Brazil.

Background: While efforts have been made to validate intrinsic capacity (IC) as a multidimensional indicator of healthy aging in high-income countries, we still need evidence from lower-income countries. We examined associations of IC with wide ranges of activities of daily living in a nationally representative sample of Brazilians aged≥50 years. Methods: This cross-sectional analysis included 7175 participants from the Brazilian Longitudinal Study of Aging. IC domains (cognitive, psychological, sensory, locomotor, and vitality) were determined using self-reported and physical performance measures. IC was operationalized through factorial analysis. We investigated associations of IC and its domains with functional ability in basic, instrumental, and advanced activities of daily living (ADL, IADL, and AADL) using logistic regressions adjusted for sociodemographic, clinical, and modifiable risk factors. Findings: The IC bi-factorial model revealed satisfactory goodness-of-fit. Preserved ability in ADL and IADL, respectively, ranged from 69% and 29% to 89% and 74% across IC quartiles. In adjusted analyses, every standard deviation increment in IC composite score was associated with almost twice the odds of preserved ADL (OR=1·72; 95%CI=1·54-1·93), preserved IADL (OR=1·95; 95%CI=1·77-2·16), and high performance in AADL (OR=1·79; 95%CI=1·59-2·00). Similar results were reported using the IC domains as predictors. Although age, race/ethnicity, and education did not modify associations of IC with functional ability, we found sex differences with stronger relationships of IC with preserved ADL or IADL in females. Interpretation: Our results support IC validity and reliability to measure healthy aging in diverse socioeconomic and cultural settings. Incorporating IC in routine practices can promote holistic and person-centered care approaches in aging societies. Funding: The Brazilian Ministry of Health and Ministry of Science, Technology, Innovation, and Communication.

Sarcopenia is associated with a greater risk of polypharmacy and number of medications: a systematic review and meta-analysis.

Polypharmacy in older adults is associated with multiple negative consequences that may affect muscular function, independently from the presence of medical conditions. The aim of this systematic review and meta-analysis was to investigate the association of sarcopenia with polypharmacy and higher number of medications. A systematic literature search of observational studies using PubMed, Web of Science, Scopus and Cochrane Library databases was conducted from inception until June 2022. To determine if sarcopenia is associated with a higher risk of polypharmacy and increased number of medications, a meta-analysis using a random-effects model was used to calculate the pooled effects (CRD42022337539). Twenty-nine studies were included in the systematic review and meta-analysis. Sarcopenia was associated with a higher prevalence of polypharmacy (odds ratio [OR]: 1.65, 95% confidence interval [CI] [1.23, 2.20], I2  = 84%, P < 0.01) and higher number of medications (mean difference: 1.39, 95% CI [0.59, 2.19], I2  = 95%, P < 0.01) compared with individuals without sarcopenia. Using meta-regression, a high variance was observed due to different populations (i.e., community-dwelling, nursing home residents, inpatients, outpatients) for both outcomes of polypharmacy (r = -0.338, SE = 0.1669, 95% CI [-0.67, -0.01], z = -2.03, P = 0.04) and number of medications (r = 0.589, SE = 0.2615, 95% CI [0.08, 1.10], z = 2.25, P = 0.02). This systematic review and meta-analysis reported a significantly increased risk of polypharmacy and higher number of medications in people with sarcopenia compared with individuals without this condition. Future research should clarify whether the specificity and number of medications is a direct contributor in accelerating the progression of muscle wasting and dysfunction contributing to sarcopenia in older adults.

Bounce Forward Better: Geriatric and Gerontological Research in the Post-pandemic Future.

In recent years, we have faced challenges in managing coronavirus disease 2019 (COVID-19), especially in older adults. The pandemic has precipitated a global health crisis that impeded older adults from maintaining their health. Disruption of the routine management of chronic diseases, physical inactivity deteriorating physical function and quality of life, malnutrition, and mental disorders have been suggested as major threats to the health of older adults. To address these problems and facilitate reactivation of normal care activities, this article summarizes the contents of a webinar held by the Annals of Geriatric Medicine and Research (AGMR) regarding the future directions of geriatric medicine and research in the post-COVID-19 era.

Effects of a 2-year exercise training on neuromuscular system health in older individuals with low muscle function.

BACKGROUND: Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, potentially determining the insurgence of sarcopenia. Evidence suggests that motoneuron and neuromuscular junction (NMJ) degeneration contribute to sarcopenia pathogenesis. Seeking for strategies able to slow down sarcopenia insurgence and progression, we investigated whether a 2-year mixed-model training involving aerobic, strength and balance exercises would be effective for improving or preserving motoneuronal health and NMJ stability, together with muscle mass, strength and functionality in an old, sarcopenic population. METHODS: Forty-five sarcopenic elderly (34 females; 11 males) with low dual-energy X-ray absorptiometry (DXA) lean mass and Short Physical Performance Battery (SPPB) score <9 were randomly assigned to either a control group [Healthy Aging Lifestyle Education (HALE), n = 21] or an intervention group [MultiComponent Intervention (MCI), n = 24]. MCI trained three times per week for 2 years with a mix of aerobic, strength and balance exercises matched with nutritional advice. Before and after the intervention, ultrasound scans of the vastus lateralis (VL), SPPB and a blood sample were obtained. VL architecture [pennation angle (PA) and fascicle length (Lf)] and cross-sectional area (CSA) were measured. As biomarkers of neuronal health and NMJ stability status, neurofilament light chain (NfL) and C-terminal agrin fragment (CAF) concentrations were measured in serum. Differences in ultrasound parameters, NfL and CAF concentration and physical performance between baseline and follow-up were tested with mixed ANOVA or Wilcoxon test. The relationship between changes in physical performance and NfL or CAF concentration was assessed through correlation analyses. RESULTS: At follow-up, MCI showed preserved VL architecture (PA, Lf) despite a reduced CSA (-8.4%, P < 0.001), accompanied by maintained CAF concentration and ameliorated overall SPPB performance (P = 0.007). Conversely, HALE showed 12.7% decrease in muscle CSA (P < 0.001), together with 5.1% and 5.5% reduction in PA and Lf (P < 0.001 and P = 0.001, respectively), and a 6.2% increase in CAF (P = 0.009) but improved SPPB balance score (P = 0.007). NfL concentration did not change in either group. In the population, negative correlations between changes in CAF concentration and SPPB total score were found (P = 0.047), whereas no correlation between NfL and SPPB variations was observed. CONCLUSIONS: The present findings suggest that our 2-year mixed aerobic, strength and balance training seemed effective for preventing the age and sarcopenia-related increases in CAF concentration, preserving NMJ stability as well as muscle structure (PA and Lf) and improving physical performance in sarcopenic older individuals.

Weight loss severity and functional decline among the oldest old in a middle-income country: The FIBRA study longitudinal findings.

BACKGROUND AND AIMS: Nutritional status is a key modifiable risk factor associated with disability, and further evidence suggests that weight change is also linked to this adverse outcome. Thus, this study aims to evaluate weight loss severity and functional decline in instrumental activities of daily living (IADL) in a seven-year period among a sample of Brazilian oldest-old adults. METHODS: Longitudinal prospective study using data from the FIBRA study (Frailty in Older Brazilians), a population-based investigation carried out in 2008/2009, with follow-up data collected in 2016/2017 from participants who were 80 years and older in the follow-up in Campinas, Brazil. Of the 167 participants with complete data in 2016-2017, 16 had improved their functional status and were excluded, so the final sample was restricted to 151 participants who maintained or declined functional status. We considered functional decline when a subject had greater IADL dependencies at follow-up than baseline. Logistic regression was performed to assess the effect of weight loss, according to severity (moderate weight loss: 5-10% of body weight; severe weight loss >10%) in increasing the number of disabilities than the group with stable weight, controlling for covariates (gender, age, education, and morbidity). An alpha level of <5% was adopted. RESULTS: During the follow-up period, 60.3% of the participants kept stable weight, 21.8% had moderate weight loss, and 17.9% had severe weight loss. During the follow-up, only severe weight loss was associated with a higher risk of functional decline (OR = 2.74; p = 0.032). CONCLUSIONS: Severe weight loss was associated with functional decline. This finding reinforces the importance of early identification of weight loss among older adults.

The Free Triiodothyronine/Free Thyroxine Ratio Is Associated with Frailty in Older Adults: A Longitudinal Multisetting Study.

Background: Various models have been proposed to predict frailty, including those based on clinical criteria and phenotypes. However, a simple biomarker associated with frailty has been not yet identified. The aim of this study is to evaluate the relationship between free triiodothyronine (fT3)/free thyroxine (fT4) ratio value and the degree of frailty among three different cohorts of older individuals: (1) acutely ill hospitalized patients, (2) nursing-home (NH) residents, and (3) home-dwelling centenarians. Methods: We performed a secondary analysis of de-identified patient-level data from two prospective observational studies on acutely hospitalized older patients (Geriatric Acute Unit [GAU]), and home-dwelling centenarians (CENT), and a retrospective-prospective observational study on older NH residents. Demographic characteristics, along with a 30-items Frailty Index (FI) and serum thyrotropin, fT3 and fT4 measurements were obtained. Results: Six hundred fifteen individuals (aged 86.4 ± 8.9 years; 55.1% females) were included in the study, including 298 (48.5%) GAU, 250 (40.6%) NH, and 67 (10.9%) CENT. A significant inverse relationship between fT3/fT4 ratio and FI values was observed (ρs = -0.17 [confidence interval; CI: -0.092 to 0.252], p < 0.001), and this was confirmed by logistic multivariate analysis (ß = -0.44, odds ratio [OR]: 0.64 [CI: 0.47-0.87], p < 0.001) (after adjustment for age, sex, and cohorts). Moreover, a progressively decreased mortality risk was associated with rising fT3/fT4 ratio (OR 0.60 [CI: 0.44-0.80] ß = -0.51, p < 0.001]. Conclusions: The fT3/fT4 ratio value was inversely correlated with frailty degree and mortality risk in a large cohort of older individuals, including centenarians, regardless of their sex and clinical condition. fT3/fT4 ratio value could represent an easily measured independent biochemical marker of frailty degree in older people.

Biochemical Markers of Musculoskeletal Health and Aging to be Assessed in Clinical Trials of Drugs Aiming at the Treatment of Sarcopenia: Consensus Paper from an Expert Group Meeting Organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d'Expérimentation en Santé (CARES SPRL), Under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of Musculoskeletal Conditions and Aging.

In clinical trials, biochemical markers provide useful information on the drug's mode of action, therapeutic response and side effect monitoring and can act as surrogate endpoints. In pharmacological intervention development for sarcopenia management, there is an urgent need to identify biomarkers to measure in clinical trials and that could be used in the future in clinical practice. The objective of the current consensus paper is to provide a clear list of biochemical markers of musculoskeletal health and aging that can be recommended to be measured in Phase II and Phase III clinical trials evaluating new chemical entities for sarcopenia treatment. A working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) proposed classifying biochemical markers into 2 series: biochemical markers evaluating musculoskeletal status and biochemical markers evaluating causal factors. For series 1, the group agreed on 4 biochemical markers that should be assessed in Phase II or Phase III trials (i.e., Myostatin-Follistatin, Brain Derived Neurotrophic Factor, N-terminal Type III Procollagen and Serum Creatinine to Serum Cystatin C Ratio - or the Sarcopenia Index). For series 2, the group agreed on 6 biochemical markers that should be assessed in Phase II trials (i.e., the hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate, and cortisol, and the inflammatory markers C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-α), and 2 in Phase III trials (i.e., IGF-I and CRP). The group also proposed optional biochemical markers that may provide insights into the mode of action of pharmacological therapies. Further research and development of new methods for biochemical marker assays may lead to the evolution of these recommendations.

Bounce Forward Better: Geriatric and Gerontological Research in the Post-pandemic Future.

In recent years, we have faced challenges in managing coronavirus disease 2019 (COVID-19), especially in older adults. The pandemic has precipitated a global health crisis that impeded older adults from maintaining their health. Disruption of the routine management of chronic diseases, physical inactivity deteriorating physical function and quality of life, malnutrition, and mental disorders have been suggested as major threats to the health of older adults. To address these problems and facilitate reactivation of normal care activities, this article summarizes the contents of a webinar held by the Annals of Geriatric Medicine and Research (AGMR) regarding the future directions of geriatric medicine and research in the post-COVID-19 era.

Comprehensive Geriatric Hospital at Home: Adaptation to Referral and Case-Mix Changes During the COVID-19 Pandemic.

OBJECTIVES: To describe the evolution of a Hospital at Home (HAH) based on comprehensive geriatric assessment (CGA), including its adaptability to changing case-mixes and pathways during the COVID-19 pandemic. DESIGN: Observational study of consecutive admissions to a combined step-up (admissions from home) and step-down (hospital discharge) HAH during 3 periods: prepandemic (2018‒February 2020) vs pandemic (March‒December 2020, and January‒December 2021). SETTING AND PARTICIPANTS: Participants were all consecutive patients admitted to a CGA-based HAH, located in Barcelona, Spain. Referrals followed acute events or exacerbation of chronic conditions, by either primary care (step-up) or after post-surgical discharge (step-down). METHODS: HAH intervention based on CGA and incorporated geriatric rehabilitation. Patient case-mix, functional evolution (Barthel index), and mortality were compared across periods and between pathways. RESULTS: HAH capacity expanded 3 fold from 15 to 45 virtual beds and altogether managed 688 consecutive patients [mean age (SD) = 82.5 (9.6) years; 59% women]. Pandemic case-mix was slightly older (mean age = 83.5 vs 82 years, P = .012) than prepandemic, with greater mobility impairment. Across periods, step-up increased (26.1%, 40.9%, 48.2%, P < .01) because of medical events, skin ulcers, and post-acute stroke, whereas step-down decreased; multivariable models showed no differences in functional improvement or mortality. When comparing pathways, step-up featured older patients with higher comorbidity, worse functional status, and lower absolute functional gain than step-down (5.6 vs 13 points of Barthel index, P < .01), remaining statistically significant after adjusting for covariates (P = .003); no differences in mortality were observed. CONCLUSIONS AND IMPLICATIONS: A multipurpose, step-down and step-up CGA HAH expanded its activity and adapted to changing case-mixes and pathways throughout COVID-19 pandemic waves. Although further quantitative and qualitative studies are needed to assess the impact of this model, our results suggest that harnessing the adaptability of HAH may help advance a paradigm shift toward more person-centered, cost-effective models of clinical care aimed at older adults.

RBDtector: an open-source software to detect REM sleep without atonia according to visual scoring criteria.

REM sleep without atonia (RSWA) is a key feature for the diagnosis of rapid eye movement (REM) sleep behaviour disorder (RBD). We introduce RBDtector, a novel open-source software to score RSWA according to established SINBAR visual scoring criteria. We assessed muscle activity of the mentalis, flexor digitorum superficialis (FDS), and anterior tibialis (AT) muscles. RSWA was scored manually as tonic, phasic, and any activity by human scorers as well as using RBDtector in 20 subjects. Subsequently, 174 subjects (72 without RBD and 102 with RBD) were analysed with RBDtector to show the algorithm's applicability. We additionally compared RBDtector estimates to a previously published dataset. RBDtector showed robust conformity with human scorings. The highest congruency was achieved for phasic and any activity of the FDS. Combining mentalis any and FDS any, RBDtector identified RBD subjects with 100% specificity and 96% sensitivity applying a cut-off of 20.6%. Comparable performance was obtained without manual artefact removal. RBD subjects also showed muscle bouts of higher amplitude and longer duration. RBDtector provides estimates of tonic, phasic, and any activity comparable to human scorings. RBDtector, which is freely available, can help identify RBD subjects and provides reliable RSWA metrics.

Differentiation of central disorders of hypersomnolence with manual and artificial-intelligence-derived polysomnographic measures.

Differentiation of central disorders of hypersomnolence (DOH) is challenging but important for patient care. This study aimed to investigate whether biomarkers derived from sleep structure evaluated both by manual scoring as well as with artificial intelligence (AI) algorithms allow distinction of patients with different DOH. We included video-polysomnography data of 40 narcolepsy type 1 (NT1), 26 narcolepsy type 2 (NT2), 23 idiopathic hypersomnia (IH) patients and 54 subjects with subjective excessive daytime sleepiness (sEDS). Sleep experts manually scored sleep stages. A previously validated AI algorithm was employed to obtain automatic hypnograms and hypnodensity graphs (where each epoch is represented as a mixture of sleep stage probabilities). One-thousand-three features describing sleep architecture and instability were extracted from manual/automatic hypnogram and hypnodensity graphs. After feature selection, random forest classifiers were trained and tested in a 5-fold-cross-validation scheme to distinguish groups pairwise (NT1-vs-NT2, NT1-vs-IH, …) and single groups from the pooled remaining ones (NT1-vs-rest, NT2-vs-rest,…). The accuracy/F1-score values obtained in the test sets were: 0.74±0.04/0.79±0.05 (NT1-vs-NT2), 0.89±0.09/0.91±0.08 (NT1-vs-IH), 0.93±0.06/0.91±0.07 (NT1-vs-sEDS), 0.88±0.04/0.80±0.07 (NT1-vs-rest), 0.65±0.10/0.70±0.09 (NT2-vs-IH), 0.72±0.12/0.60±0.10 (NT2-vs-sEDS), 0.54±0.19/0.38±0.13 (NT2-vs-rest), 0.57±0.11/0.35±0.18 (IH-vs-sEDS), 0.71±0.08/0.35±0.10 (IH-vs-rest) and 0.76±0.08/0.71±0.13 (sEDS-vs-rest). The results confirm previous findings on sleep instability in NT1 patients and show that combining manual and automatic AI-based sleep analysis could be useful for better distinction of NT2 from IH, but no precise sleep biomarker of NT2 or IH could be identified. Validation in a larger and multi-centric cohort is needed to confirm these findings.

Lower-Limb Muscle Power Is Negatively Associated with Protein Intake in Older Adults: A Cross-Sectional Study.

The present study examined the association between lower-limb muscle power and protein-related parameters in older adults. This study followed a cross-sectional design. Participants were community-dwelling older adults. Candidates were considered eligible if they were 60 years or older, lived independently, and possessed sufficient physical and cognitive abilities to perform all the measurements required by the protocol. The 5 times sit-to-stand (5STS) test was performed as fast as possible according to a standard protocol. Absolute, relative, and allometric muscle power measures were estimated using 5STS-based equations. Diet was assessed by 24-h dietary recall and diet composition was estimated using a nutritional software. One-hundred and ninety-seven older adults participated to the present study. After adjustment for covariates, absolute and allometric muscle power were negatively associated with body weight-adjusted protein intake. Our findings indicate that absolute and allometric muscle power estimated through a simple equation are negatively associated with body weight-adjusted protein intake in community-dwelling older adults.

WHO working definition of vitality capacity for healthy longevity monitoring.

Intrinsic capacity, a crucial concept in healthy ageing, is defined by WHO as "the composite of all the physical and mental capacities that an individual can draw on at any point in time". Vitality capacity is considered the underlying physiological determinant of intrinsic capacity. To advance the measurement and monitoring of vitality capacity, a working group of WHO staff members and twenty experts representing six WHO regions was convened to discuss and clarify the attributes of vitality capacity and to develop a clear working definition of the concept. Potential biomarkers to measure vitality capacity were identified, and the following consensual working definition was developed: vitality capacity is a physiological state (due to normal or accelerated biological ageing processes) resulting from the interaction between multiple physiological systems, reflected in (the level of) energy and metabolism, neuromuscular function, and immune and stress response functions of the body.

Delirium as late manifestation of infective endocarditis after transcatheter aortic valve implantation.

More than one-third of the cases of infective endocarditis (IE) occur in older patients. The disease is often characterized by atypical symptoms. The incidence of neurological complications is high and represents a strong independent predictor of severe outcomes and mortality. IE is a rare but serious complication of transcatheter aortic valve implantation (TAVI). A persistent delirium as a unique manifestation of post-TAVI IE in an older patient is presented in this clinical case.

Frailty in kidney transplantation: a review on its evaluation, variation and long-term impact.

The problem of frailty in kidney transplantation is an increasingly discussed topic in the transplant field, partially also generated by the multiple comorbidities by which these patients are affected. The criteria currently used to establish the presence and degree of frailty can be rapidly assessed in clinical practice, even in patients with chronic kidney disease (CKD). The main objectives of this work are: (i) to describe the method of evaluation and the impact that frailty has in patients affected by CKD, (ii) to explore how frailty should be studied in the pre-transplant evaluation, (iii) how frailty changes after a transplant and (iv) the impact frailty has over the long term on the survival of renal transplant patients.

When the Pandemic Will Be Over: Lots of Hope and Some Concerns.

The COVID-19 pandemic significantly threatened healthcare systems worldwide. The worst-hit population has been represented by older people with underlying chronic comorbidities, while children and adolescents developed mild or asymptomatic forms of the disease. However, certain medical conditions (i.e., obesity, respiratory, or neurological or immune disorders) may increase the risk for poor health outcomes even in young and middle-aged people. Beyond the direct negative effects of the infection, the pandemic posed several health challenges through an increase in psycho-social issues (i.e., anxiety, depression, fatigue, sleep alterations, loneliness, reduced assistance, and loss of income). Accordingly, the pandemic is negatively impacting the accumulation of the functional reserves of each individual, starting from early life. With the long-term effects of the pandemic to be seen in the coming years, clinicians must be prepared to manage such high clinical complexity of people they encounter, through the implementation of multidimensional and multidisciplinary interventions.

Geriatric syndromes and functions in older adults with COVID-19 hospitalized in sub-acute care: a multicenter study.

OBJECTIVE: Alternatives to conventional acute hospitalizations have been particularly useful during the COVID-19 pandemic. However, little is known on the management and outcomes of COVID-19 in older patient admitted to non-acute settings. The main aim of this study was to determine the effect of geriatrics syndromes on functional outcomes in older COVID-19 patients cared in sub-acute units. METHODS: Prospective multicenter observational cohort study of patients aged 65 years and older with COVID-19, admitted to sub-acute units in Italy and Spain. Multivariable logistic regression models were used to test the association between geriatric syndromes and other clinical variables, and the functional status at discharge, defined by a Barthel Index > = 80. RESULTS: A total of 158 patients were included in the study with a median age of 82 [Interquartile Range 81, 83]; of these 102 (65%) patients had a Barthel Index ≥ 80 at discharge. In the main multivariable logistic regression model a higher severity of frailty-measured with the Clinical Frailty Scale-(OR 0.30; CI 0.18-0.47), and the presence of delirium (OR 0.04; CI 0.00-0.35) at admission were associated with lower odds of a higher functional status at discharge. Other variables associated with lower functional status were female gender (OR 0.36; CI 0.13-0.96), and a higher number of comorbidities (OR 0.48; CI 0.26-0.82). CONCLUSION: The study reports a relatively high prevalence of functional recovery for older COVID-19 patients admitted to sub-acute units. Additionally, it underlines the importance of targeting geriatrics syndromes, in particular frailty and delirium, for their possible effects on functional recovery.