Hospitalization costs in Portugal among people with obesity: results from a nationwide population-based cohort 2011 to 2021.

Background: Obesity has been extensively studied over the years, primarily focusing on the physiological aspects of the disease. However, the general burden of obesity mainly the financial implications and its influence on hospitalization and length of stay have only recently garnered attention in the literature, particularly in the case of Portugal. Aim: This study aimed to investigate the association between obesity and hospitalizations in the Portuguese adult population and compare the average costs of hospitalization among participants with and without obesity. Methods: At baseline, the analytic sample consisted of 10,102 participants aged ≥18 years from the Portuguese population-based Epidemiology of Chronic Diseases Cohort (EpiDoC). Participants were then followed for up to 10 years from 2011 to 2021 in three more waves of data collection. Body mass index was derived from self-reported weight and height, and instances of hospitalization were self-reported by the participants. The associated costs for each hospitalization episode were categorized according to national legislation and valued according to the pricing for Diagnosis Related Groups. Results: Obesity was associated with more hospitalizations (for example, Obesity class I vs. normal weight: OR = 1.33 [1.14-1.55]). However, when the presence of multimorbidity was considered, this association diminished. While longer hospital length of stay was observed in individuals with higher obesity categories, this difference did not reach statistical significance. On average, the total hospitalization costs per patient with obesity amounted to €200.4 per year. Conclusion: Obesity is as a risk factor for hospitalizations and potentially with higher length of stay hospitalizations, with this effect being partially mediated by the concurrent presence of multimorbidity. Consequently, obesity constitutes an additional burden on healthcare systems. This underscores the imperative of implementing cost-effective prevention programs aimed at addressing and managing this significant public health concern.

Paratesticular Cellular Angiofibroma (CAF): A Rare Case Report.

Cellular angiofibromas (CAFs) are infrequent and benign soft-tissue tumors that primarily affect the genitourinary region in both genders. The authors report the case of a 71-year-old male patient who exhibited progressively increasing swelling in both testicles, with greater prominence noted on the left side. Initial findings from physical examination and scrotal ultrasound indicated the possibility of bilateral hydrocele, so the patient was recommended surgical intervention of the left more prominent side. Intraoperatively, a left paratesticular mass was identified and subsequently excised. Histopathological analysis confirmed the diagnosis of cellular angiofibroma. Surgeons should be cognizant of this tumor type to optimize treatment strategies, as local excision demonstrates a potential to preserve the testicle and yield favorable outcomes. Although occurrences of local recurrence are extremely rare, long-term follow-up is imperative.

Trajectories and determinants of ageing in Portugal: insights from EpiDoC, a nationwide population-based cohort.

INTRODUCTION: The population in Portugal is ageing due to increased life expectancy and reduced fertility rates. We aimed to estimate the health trajectories of Portuguese older adults (60 + years old) in a 10-year period and to assess associated sociodemographic, lifestyle factors and multimorbidity status. METHODS: Using the population-based EpiDoC cohort, we estimated the trajectories of health-related quality of life and physical function of 4135 Portuguese older adults over 10 years using linear mixed models. Factors associated to health-related quality of life and physical function were assessed using linear mixed models and random intercept tobit regression, respectively. RESULTS: The physical disability of participants increased by 0.263 (0.240, 0.286), and health-related quality of life declined by 0.074 (-0.084, -0.063), over 10 years. With advancing age, older adults reported a faster reduction in health-related quality of life and faster increase in physical disability. In general, women were in worse health than men at baseline, albeit with a similar rate of change throughout the follow-up. Higher education and regular exercise were associated with better health-related quality of life and physical function while multimorbidity and excess weight were associated with worse reporting of these outcomes. CONCLUSIONS: These findings, based on longitudinal data with 10 years of follow-up, are essential to effectively plan resource allocation, plan better healthcare and design informed public health policies in Portugal. This study characterizes ageing in Portugal showing increased physical disability and decreased health-related quality of life with advancing age older adults, helping to develop public health policies.

Associations between appetite, physical activity and sedentary behaviour from hip- and wrist-worn accelerometers in community-dwelling older adults.

AIM: The objective of the current study was to examine whether physical activity and sedentary behavior were associated with appetite among community-dwelling older adults. METHODS: Cross-sectional analysis was performed on three cohort studies: the Longitudinal Aging Study Amsterdam (LASA); the Health, Aging and Body Composition Study (HABC Study) and the I'm Still Standing Study (ISS Study); (n = 1173, n = 162, n = 125; age range: 57-99, 85-95, 80-100 years; women: 51%, 56%, 61%, respectively). Physical activity and sedentary behavior were measured using hip-worn (LASA and HABC) and wrist-worn (ISS) accelerometers. Appetite was self-reported. Logistic regression models were fitted by accelerometer placement to explore the association between good appetite and various physical activity metrics (total activity, sedentary behavior, and time spent in different intensities of physical activity). RESULTS: Among cohorts using hip-worn accelerometers, those having total activity within the highest tertile had more than double the odds of having good appetite compared with those within the lowest tertile (odds ratio [OR] 2.16 (1.15-4.06)). Each additional percent of daily sedentary behavior decreased the odds for having good appetite by 3% (OR 0.97 (0.95-0.996)), while each additional percent of daily light-intensity physical activity increased the odds for having good appetite by 4% (OR 1.02 (1.01-1.06)). No association was found between either physical activity or sedentary behavior and appetite for measurements with the wrist-worn accelerometers. CONCLUSIONS: Among community-dwelling older adults, the associations between appetite, accelerometer-assessed physical activity and sedentary behavior differ by accelerometer placement location. This study highlights the importance of careful interpretation of accelerometer data from different body locations and concurrent health outcomes. Geriatr Gerontol Int 2023; 23: 411-417.

A Core Outcome Set for nutritional intervention studies in older adults with malnutrition and those at risk: a study protocol.

BACKGROUND: Malnutrition (i.e., protein-energy malnutrition) in older adults has severe negative clinical consequences, emphasizing the need for effective treatments. Many, often small, randomized controlled trials (RCTs) testing the effectiveness of nutritional interventions for the treatment of malnutrition showed mixed results and a need for meta-analyses and data pooling has been expressed. However, evidence synthesis is hampered by the wide variety of outcomes and their method of assessment in previous RCTs. This paper describes the protocol for developing a Core Outcome Set (COS) for nutritional intervention studies in older adults with malnutrition and those at risk. METHODS: The project consists of five phases. The first phase consists of a scoping review to identify frequently used outcomes in published RCTs and select additional patient-reported outcomes. The second phase includes a modified Delphi Survey involving experienced researchers and health care professionals working in the field of malnutrition in older adults, followed by the third phase consisting of a consensus meeting to discuss and agree what critical outcomes need to be included in the COS. The fourth phase will determine how each COS outcome should be measured based on a systematic literature review and a second consensus meeting. This will be followed by a dissemination and implementation phase. Patient and Public Involvement (PPI) representatives will contribute to study design, oversight, consensus, and dissemination. CONCLUSIONS: The result of this project is a COS that should be included in any RCT evaluating the effect of nutritional interventions in older adults with malnutrition and those at risk. This COS will facilitate comparison of RCT results, will increase efficient use of research resources and will reduce bias due to measurement of the outcome and publication bias. Ultimately, the COS will support clinical decision making by identifying the most effective approaches for treating and preventing malnutrition in older adults.

Association of physical activity with physical function and quality of life in people with hip and knee osteoarthritis: longitudinal analysis of a population-based cohort.

Hip and knee osteoarthritis (HKOA) is a chronic disease characterized by joint pain that leads to reduced physical function and health-related quality of life (HRQoL). At present, no cure is available. Clinical trials indicate that people with HKOA benefit from physical activity in several health-related outcomes. However, few studies have evaluated the long-term positive effect of regular physical activity. This study analyzed participants with HKOA from a nationwide population-based cohort (EpiDoC Cohort) to assess the impact of physical activity on patients' physical function and HRQoL over a long-term follow-up. The regular weekly frequency of intentional physical activity was self-reported as non-frequent (0 times/week), frequent (1-2 times/week), or very frequent (≥ 3 times/week). This study followed 1086 participants over a mean period of 4.7 ± 3.4 years, during which 6.3% and 14.9% of participants reported frequent and very frequent physical activity, respectively. Using linear mixed models, we found that frequent (ß = - 0.101 [- 0.187, - 0.016]; ß = 0.039 [- 0.002, 0.080]) and very frequent physical activity (ß = - 0.061 [- 0.118, - 0.004]; ß = 0.057 [0.029, 0.084]) were associated with improved physical function and HRQoL over time, respectively, when compared with non-frequent exercise, adjusting for years to baseline, sex, age, years of education, body mass index, multimorbidity, hospitalizations, clinical severity, and unmanageable pain levels. These findings raise awareness of the importance of maintaining exercise/physical activity long term to optimize HRQoL and physical function. Further studies must address barriers and facilitators to improve the adoption of regular physical activity among citizens with HKOA.

A Web-Based Self-help Intervention for Coping With the Loss of a Partner: Protocol for Randomized Controlled Trials in 3 Countries.

BACKGROUND: The death of a partner is a critical life event in later life, which requires grief work as well as the development of a new perspective for the future. Cognitive behavioral web-based self-help interventions for coping with prolonged grief have established their efficacy in decreasing symptoms of grief, depression, and loneliness. However, no study has tested the efficacy for reducing grief after losses occurring less than 6 months ago and the role of self-tailoring of the content. OBJECTIVE: This study aims to evaluate the clinical efficacy and acceptance of a web-based self-help intervention to support the grief process of older adults who have lost their partner. It will compare the outcomes, adherence, and working alliance in a standardized format with those in a self-tailored delivery format and investigate the effects of age, time since loss, and severity of grief at baseline as predictors. Focus groups to understand user experience and a cost-effectiveness analysis will complement the study. METHODS: The study includes 3 different randomized control trials. The trial in Switzerland comprises a waitlist control group and 2 active arms consisting of 2 delivery formats, standardized and self-tailored. In the Netherlands and in Portugal, the trials follow a 2-arm design that will be, respectively, complemented with focus groups on technology acceptance and cost-effectiveness analysis. The main target group will consist of adults aged >60 years from the general population in Switzerland (n≥85), the Netherlands (n≥40), and Portugal (n≥80) who lost their partner and seek help for coping with grief symptoms, psychological distress, and adaptation problems in daily life. The trials will test the intervention's clinical efficacy for reducing grief (primary outcome) and depression symptoms and loneliness (secondary outcomes) after the intervention. Measurements will take place at baseline (week 0), after the intervention (week 10), and at follow-up (week 20). RESULTS: The trials started in March 2022 and are expected to end in December 2022 or when the needed sample size is achieved. The first results are expected by January 2023. CONCLUSIONS: The trials will provide insights into the efficacy and acceptance of a web-based self-help intervention among older adults who have recently lost a partner. Results will extend the knowledge on the role of self-tailoring, working alliance, and satisfaction in the effects of the intervention. Finally, the study will suggest adaptations to improve the acceptance of web-based self-help interventions for older mourners and explore the cost-effectiveness of this intervention. Limitations include a self-selective sample and the lack of cross-cultural comparisons. TRIAL REGISTRATION: Switzerland: ClinicalTrials.gov NCT05280041; https://clinicaltrials.gov/ct2/show/NCT05280041; Portugal: ClinicalTrials.gov NCT05156346; https://clinicaltrials.gov/ct2/show/NCT05156346. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/37827.

Animal foods and mobility limitations in community-dwelling young-old adults: longitudinal analysis of the EpiDoC cohort.

BACKGROUND: Nutrition and particularly protein play a role in optimally stimulating muscle protein synthesis and maintaining function. Animal foods are excellent sources of high-quality protein. Therefore, we aimed to determine the association between the consumption of animal foods and mobility limitations in young-old adults. METHODS: The analytic sample was composed of 2860 community-dwelling adults aged 50 and over from a nationally representative longitudinal cohort of Portuguese adults who were followed up to 2.7 years. An animal food intake score was derived from the frequency of consumption of meat, fish, and dairy products. Mobility limitations were defined as the difficulty standing up from a chair, walking, and climbing stairs. To determine the association between animal food intake and mobility limitations mixed effects logistic models were fitted. RESULTS: Associations between quartiles of animal food intake and mobility limitations (for example, for walking outdoors Quartile 4 v Q1: OR: 0.29; 95%CI: 0.15, 0.56) in unadjusted models were present, but there was no difference in the rate of change of mobility limitations over time in unadjusted models. These associations were no longer present when models were adjusted for sociodemographic, lifestyle and health variables. For example, participants in Q4 of animal food intake were not more or less likely to have difficulty climbing stairs than those in Q1 (OR: 0.95; 95%CI: 0.65, 1.38) nor have a different rate of change over time (OR: 0.86; 95%CI: 0.54, 1.37). CONCLUSIONS: No convincing evidence was found to support an effect of animal foods intake measured at baseline on self-reported mobility limitations over a short period of time.

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

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

Obesity- attributable costs of absenteeism among working adults in Portugal.

BACKGROUND: Obesity leads to poor health outcomes and may adversely affect work productivity. This study, aimed to investigate the obesity- attributable costs of absenteeism among working adults in Portugal. METHODS: The study population included individuals actively working at baseline from the Epidemiology of Chronic Diseases Cohort (EpiDoC), a large Portuguese population-based prospective study. Body mass index was measured at baseline and in two follow-up interviews. Absenteeism in each wave of the EpiDoC was assessed by the question "Did you have a sick leave in the previous 12 months? yes/no", followed by "How many days did you miss work due to sickness in the previous twelve months?". Body mass index (BMI) was classified into underweight, normal weight, overweight, and obese, based on the standard World Health Organization definition. Association between obesity and absenteeism was estimated with the negative binomial regression model adjusted for BMI, chronic diseases, and lifestyle. Obesity- attributable costs were calculated using lost gross income during the time absent from work, through the human-capital approach. RESULTS: The EpiDoC included 4338 working adults at baseline. Of these, 15.2% were obese at the beginning of the study and 22.7% of the population had been absent from work in the last 12 months. Participants with obesity missed 66% more days at work (IRR: 1.66; CI 95%:1.13-2.44; (p = 0.009.) than those with normal weight. The odds of having been absent from work were 1.4 times higher in obese compared to non-obese individuals (CI 95%: 1.18-1.67; p < 0.01) adjusted to sex and type of work. Obese individuals missed 3.8 more days per year than those with normal weight (95%CI: 3.1-4.5). Extrapolating to the entire Portuguese working population, absenteeism due to obesity incurred an additional cost of €238 million per year. CONCLUSION: Obesity imposes a financial burden due to absenteeism in Portugal. Employers and national health regulators should seek effective ways to reduce these costs.

Low Adherence to the Mediterranean Diet Is Associated with Poor Socioeconomic Status and Younger Age: A Cross-Sectional Analysis of the EpiDoC Cohort.

The Mediterranean diet (MD) is recognized as one of the healthiest dietary patterns as it has been consistently associated with several beneficial health outcomes. Adherence to the MD pattern has been decreasing in southern European countries for the last decades, especially among low socioeconomic groups. The aim of this study was to assess the adherence to the MD in Portugal, to evaluate regional differences, and explore associated factors (sociodemographic, economic, and lifestyles behaviors). This study used the third data collection wave of the Epidemiology of Chronic Diseases Cohort Study (EpiDoC 3). MD adherence was assessed using the Portuguese-validated MD adherence score (MEDAS) questionnaire. Non-adjusted and adjusted logistic regression models were used to assess the risk factors for low MD adherence and individual MEDAS items. In this cross-sectional evaluation of the EpiDoC 3 cohort study (n = 5647), 28.8% of the Portuguese population had low adherence to a MD. Azores and Madeira had lower adherence to the MD than the rest of the country. Younger individuals in lower income categories (e.g., ORfinding it very difficult = 1.48; 95% CI 1.16-1.91) and with a lower educational level (e.g., OR0-4 years = 2.63; 95% CI 2.09-3.32) had higher odds of having a lower adherence to the MD. Portuguese adults have a high prevalence of low adherence to the MD, especially among those who are younger and have lower socioeconomic status. Public health policies to promote adherence to the MD should pay special attention to these groups.

Persistence of IgG COVID-19 antibodies: A longitudinal analysis.

Background and aim: The kinetics of antibody production in response to coronavirus disease 2019 (COVID-19) infection is not well-defined yet. This study aimed to evaluate the antibody responses to SARS-CoV-2 and its dynamics during 9-months in a cohort of patients infected during the first phase of the pandemic. As a secondary aim, it was intended to evaluate the factors associated with different concentrations of IgG antibodies. Methods: A prospective cohort study was conducted from June 2020 to January 2021. This study recruited a convenience sample of adult individuals who where recently diagnosed with COVID-19 and were living in mainland Portugal. A total of 1,695 blood samples were collected from 585 recovered COVID-19 patients up to 9 months after SARS-CoV-2 acute infection. A blood sample was collected at baseline and three, 6 and 9 months after SARS-CoV-2 acute infection to assess the concentration of IgG antibody against SARS-CoV-2. Results: The positivity rate of IgG reached 77.7% in the first 3 months after symptom onset. The IgG persists at all subsequent follow-up time-points, which was 87.7 and 89.2% in the 6th and 9th months after symptom onset, respectively. Three distinct kinetics of antibody response were found within the 9 months after infection. Kinetic 1 (K1) was characterized by a constant low IgG antibody concentration kinetic (group size: 65.2%); kinetic 2 (K2), composed by constant moderate IgG kinetic (group size: 27.5%) and kinetic 3 (K3) characterized by higher IgG kinetic (group size: 7.3%). People with ≥56 years old (OR: 3.33; CI 95%: [1.64; 6.67]; p-value: 0.001) and symptomatic COVID-19 (OR: 2.08; CI 95%: [1.08; 4.00]; p-value: 0.031) had higher odds of a "Moderate IgG kinetic." No significant association were found regarding the "Higher IgG kinetic." Conclusion: Our results demonstrate a lasting anti-spike (anti-S) IgG antibody response at least 9 months after infection in the majority of patients with COVID-19. Younger participants with asymptomatic disease have lower IgG antibody positivity and possibly more susceptible to reinfection. This information contributes to expanding knowledge of SARS-CoV-2 immune response and has direct implications in the adoption of preventive strategies and public health policies.

The Association between 25-Hydroxyvitamin D Concentration and Telomere Length in the Very-Old: The Newcastle 85+ Study.

(1) Introduction: vitamin D may maintain the telomere length, either directly or via the inflammation effect and/or modulating the rate of cell proliferation. Whilst results from cross-sectional studies investigating the association between 25(OH)D concentration and telomere length have been mixed, there is a dearth of data from prospective studies which have assessed these associations. This study aimed to examine the association between 25(OH)D concentration in plasma and telomere length in blood cells in very-old adults (≥85 years old) at baseline, 18 months and 36 months by controlling for related lifestyle factors. (2) Methodology: our prospective cohort study comprised 775 participants from the Newcastle 85+ Study who had 25(OH)D measurements at baseline. Plasma 25(OH)D was stratified as <25 nmol/L (low), 25-50 nmol/L (moderate) and >50 nmol/L (high). Peripheral blood mononuclear cell telomere length was measured by quantitative real-time polymerase chain reaction at baseline, 18 and 36 months from baseline. (3) Results: a positive significant association was found between 25(OH)D concentration and telomere length amongst very-old participants at baseline (95% CI = 12.0-110.3, B = 61.2 ± 5.0, p = 0.015). This association was negative at 18 months (95% CI = -59.9--7.5, B = -33.7 ± 13.3, p = 0.012) but was non-significant at 36 months. (4) Conclusion: Circulating 25(OH)D concentration shows inconsistent relationships with telomere length over time in very-old (85+ year old) adults.

Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy type 1 (STR1VE-EU): an open-label, single-arm, multicentre, phase 3 trial.

BACKGROUND: Spinal muscular atrophy is a rare, autosomal recessive, neuromuscular disease caused by biallelic loss of the survival motor neuron 1 (SMN1) gene, resulting in motor neuron dysfunction. In this STR1VE-EU study, we aimed to evaluate the safety and efficacy of onasemnogene abeparvovec gene replacement therapy in infants with spinal muscular atrophy type 1, using broader eligibility criteria than those used in STR1VE-US. METHODS: STR1VE-EU was a multicentre, single-arm, single-dose, open-label phase 3 trial done at nine sites (hospitals and universities) in Italy (n=4), the UK (n=2), Belgium (n=2), and France (n=1). We enrolled patients younger than 6 months (180 days) with spinal muscular atrophy type 1 and the common biallelic pathogenic SMN1 exon 7-8 deletion or point mutations, and one or two copies of SMN2. Patients received a one-time intravenous infusion of onasemnogene abeparvovec (1·1 × 1014 vector genomes [vg]/kg). The outpatient follow-up consisted of assessments once per week starting at day 7 post-infusion for 4 weeks and then once per month until the end of the study (at age 18 months or early termination). The primary outcome was independent sitting for at least 10 s, as defined by the WHO Multicentre Growth Reference Study, at any visit up to the 18 months of age study visit, measured in the intention-to-treat population. Efficacy was compared with the Pediatric Neuromuscular Clinical Research (PNCR) natural history cohort. This trial is registered with ClinicalTrials.gov, NCT03461289 (completed). FINDINGS: From Aug 16, 2018, to Sept 11, 2020, 41 patients with spinal muscular atrophy were assessed for eligibility. The median age at onasemnogene abeparvovec dosing was 4·1 months (IQR 3·0-5·2). 32 (97%) of 33 patients completed the study and were included in the ITT population (one patient was excluded despite completing the study because of dosing at 181 days). 14 (44%, 97·5% CI 26-100) of 32 patients achieved the primary endpoint of functional independent sitting for at least 10 s at any visit up to the 18 months of age study visit (vs 0 of 23 untreated patients in the PNCR cohort; p<0·0001). 31 (97%, 95% CI 91-100) of 32 patients in the ITT population survived free from permanent ventilatory support at 14 months compared with six (26%, 8-44) of 23 patients in the PNCR natural history cohort (p<0·0001). 32 (97%) of 33 patients had at least one adverse event and six (18%) had adverse events that were considered serious and related to onasemnogene abeparvovec. The most common adverse events were pyrexia (22 [67%] of 33), upper respiratory infection (11 [33%]), and increased alanine aminotransferase (nine [27%]). One death, unrelated to the study drug, occurred from hypoxic-ischaemic brain damage because of a respiratory tract infection during the study. INTERPRETATION: STR1VE-EU showed efficacy of onasemnogene abeparvovec in infants with symptomatic spinal muscular atrophy type 1. No new safety signals were identified, but further studies are needed to show long-term safety. The benefit-risk profile of onasemnogene abeparvovec seems favourable for this patient population, including those with severe disease at baseline. FUNDING: Novartis Gene Therapies.

Nutrition and Frailty: Opportunities for Prevention and Treatment.

Frailty is a syndrome of growing importance given the global ageing population. While frailty is a multifactorial process, poor nutritional status is considered a key contributor to its pathophysiology. As nutrition is a modifiable risk factor for frailty, strategies to prevent and treat frailty should consider dietary change. Observational evidence linking nutrition with frailty appears most robust for dietary quality: for example, dietary patterns such as the Mediterranean diet appear to be protective. In addition, research on specific foods, such as a higher consumption of fruit and vegetables and lower consumption of ultra-processed foods are consistent, with healthier profiles linked to lower frailty risk. Few dietary intervention studies have been conducted to date, although a growing number of trials that combine supplementation with exercise training suggest a multi-domain approach may be more effective. This review is based on an interdisciplinary workshop, held in November 2020, and synthesises current understanding of dietary influences on frailty, focusing on opportunities for prevention and treatment. Longer term prospective studies and well-designed trials are needed to determine the causal effects of nutrition on frailty risk and progression and how dietary change can be used to prevent and/or treat frailty in the future.

Association of Daily Physical Activity and Sedentary Behaviour with Protein Intake Patterns in Older Adults: A Multi-Study Analysis across Five Countries.

Physical activity and protein intake are associated with ageing-related outcomes, including loss of muscle strength and functional decline, so may contribute to strategies to improve healthy ageing. We investigated the cross-sectional associations between physical activity or sedentary behaviour and protein intake patterns in community-dwelling older adults across five countries. Self-reported physical activity and dietary intake data were obtained from two cohort studies (Newcastle 85+ Study, UK; LiLACS, New Zealand Maori and Non-Maori) and three national food consumption surveys (DNFCS, The Netherlands; FINDIET, Finland; INRAN-SCAI, Italy). Associations between physical activity and total protein intake, number of eating occasions providing protein, number of meals with specified protein thresholds, and protein intake distribution over the day (calculated as a coefficient of variance) were assessed by regression and repeated measures ANOVA models adjusting for covariates. Greater physical activity was associated with higher total protein intake and more eating occasions containing protein, although associations were mostly explained by higher energy intake. Comparable associations were observed for sedentary behaviour in older adults in Italy. Evidence for older people with higher physical activity or less sedentary behaviour achieving more meals with specified protein levels was mixed across the five countries. A skewed protein distribution was observed, with most protein consumed at midday and evening meals without significant differences between physical activity or sedentary behaviour levels. Findings from this multi-study analysis indicate there is little evidence that total protein and protein intake patterns, irrespective of energy intake, differ by physical activity or sedentary behaviour levels in older adults.

Dietary Protein Intake and Transition between Frailty States in Octogenarians Living in New Zealand.

Adequate nutritional status may influence progression to frailty. The purpose of this study is to determine the prevalence of frailty and examine the relationship between dietary protein intake and the transition between frailty states and mortality in advanced age. We used data from a longitudinal cohort study of Maori (80-90 years) and non-Maori (85 years). Dietary assessments (24-h multiple pass dietary recalls) were completed at the second year of follow-up (wave 2 and forms the baseline in this study). Frailty was defined using the Fried Frailty criteria. Multi-state modelling examined the association of protein intake and transitions between frailty states and death over four years. Over three quarters of participants were pre-frail or frail at baseline (62% and 16%, respectively). Those who were frail had a higher co-morbidity (p < 0.05), where frailty state changed, 44% showed a worsening of frailty status (robust → pre-frail or pre-frail → frail). Those with higher protein intake (g/kg body weight/day) were less likely to transition from robust to pre-frail [Hazard Ratio (95% Confidence Interval): 0.28 (0.08-0.91)] but also from pre-frail to robust [0.24 (0.06-0.93)]. Increased protein intake was associated with lower risk of transitioning from pre-frailty to death [0.19 (0.04-0.80)], and this association was moderated by energy intake [0.22 (0.03-1.71)]. Higher protein intake in this sample of octogenarians was associated with both better and worse outcomes.

Low protein intake, physical activity, and physical function in European and North American community-dwelling older adults: a pooled analysis of four longitudinal aging cohorts.

BACKGROUND: Dietary protein may slow the decline in muscle mass and function with aging, making it a sensible candidate to prevent or modulate disability progression. At present, studies providing reliable estimates of the association between protein intake and physical function, and its interaction with physical activity (PA), in community-dwelling older adults are lacking. OBJECTIVES: We investigated the longitudinal relation between protein intake and physical function, and the interaction with PA. METHODS: We undertook a pooled analysis of individual participant data from cohorts in the PROMISS (PRevention Of Malnutrition In Senior Subjects in the European Union) consortium (the Health Aging and Body Composition Study, Quebec Longitudinal Study on Nutrition and Successful Aging, Longitudinal Aging Study Amsterdam, and Newcastle 85+) in which 5725 community-dwelling older adults were followed up to 8.5 y. The relation between protein intake and walking speed was determined using joint models (linear mixed-effects and Cox proportional hazards models) and the relation with mobility limitation was investigated using multistate models. RESULTS: Higher protein intake was modestly protective of decline in walking speed in a dose-dependent manner [e.g., protein intake ≥1.2 compared with 0.8 g/kg adjusted body weight (aBW)/d: ß = 0.024, 95% CI: 0.009, 0.032 SD/y], with no clear indication of interaction with PA. Participants with protein intake ≥0.8 g/kg aBW/d had also a lower likelihood of incident mobility limitation, which was observed for each level of PA. This association seemed to be dose-dependent for difficulty walking but not for difficulty climbing stairs. No associations between protein intake and other mobility limitations transitions were observed. CONCLUSIONS: Higher daily protein intake can reduce physical function decline not only in older adults with protein intake below the current RDA of 0.8 g/kg BW/d, but also in those with a protein intake that is already considered sufficient. This dose-dependent association was observed for each level of PA, suggesting no clear synergistic association between protein intake and PA in relation to physical function.

Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial.

BACKGROUND: Progressive supranuclear palsy is a neurodegenerative disorder associated with tau protein aggregation. Tilavonemab (ABBV-8E12) is a monoclonal antibody that binds to the N-terminus of human tau. We assessed the safety and efficacy of tilavonemab for the treatment of progressive supranuclear palsy. METHODS: We did a phase 2, multicentre, randomised, placebo-controlled, double-blind study at 66 hospitals and clinics in Australia, Canada, France, Germany, Italy, Japan, Spain, and the USA. Participants (aged ≥40 years) diagnosed with possible or probable progressive supranuclear palsy who were symptomatic for less than 5 years, had a reliable study partner, and were able to walk five steps with minimal assistance, were randomly assigned (1:1:1) by interactive response technology to tilavonemab 2000 mg, tilavonemab 4000 mg, or matching placebo administered intravenously on days 1, 15, and 29, then every 28 days through to the end of the 52-week treatment period. Randomisation was done by the randomisation specialist of the study sponsor, who did not otherwise participate in the study. The sponsor, investigators, and participants were unaware of treatment allocations. The primary endpoint was the change from baseline to week 52 in the Progressive Supranuclear Palsy Rating Scale (PSPRS) total score in the intention-to-treat population. Adverse events were monitored in participants who received at least one dose of study drug. Prespecified interim futility criteria were based on a model-based effect size of 0 or lower when 60 participants had completed the 52-week treatment period and 0·12 or lower when 120 participants had completed the 52-week treatment period. This study is registered at ClinicalTrials.gov, number NCT02985879. FINDINGS: Between Dec 12, 2016, and Dec 31, 2018, 466 participants were screened, 378 were randomised. The study was terminated on July 3, 2019, after prespecified futility criteria were met at the second interim analysis. A total of 377 participants received at least one dose of study drug and were included in the efficacy and safety analyses (2000 mg, n=126; 4000 mg, n=125; placebo, n=126). Least squares mean change from baseline to week 52 in PSPRS was similar in all groups (between-group difference vs placebo: 2000 mg, 0·0 [95% CI -2·6 to 2·6], effect size 0·000, p>0·99; 4000 mg, 1·0 [-1·6 to 3·6], -0·105, p=0·46). Most participants reported at least one adverse event (2000 mg, 111 [88%]; 4000 mg, 111 [89%]; placebo, 108 [86%]). Fall was the most common adverse event (2000 mg, 42 [33%]; 4000 mg, 54 [43%]; placebo, 49 [39%]). Proportions of patients with serious adverse events were similar among groups (2000 mg, 29 [23%]; 4000 mg, 34 [27%]; placebo, 33 [26%]). Fall was the most common treatment-emergent serious adverse event (2000 mg, five [4%]; 4000 mg, six [5%]; placebo, six [5%]). 26 deaths occurred during the study (2000 mg, nine [7%]; 4000 mg, nine [7%]; placebo, eight [6%]) but none was drug related. INTERPRETATION: A similar safety profile was seen in all treatment groups. No beneficial treatment effects were recorded. Although this study did not provide evidence of efficacy in progressive supranuclear palsy, the findings provide potentially useful information for future investigations of passive immunisation using tau antibodies for progressive supranuclear palsy. FUNDING: AbbVie Inc.