Impact of EASO/ESPEN-Defined Sarcopenic Obesity Following a Technology-Based Weight Loss Intervention.

BACKGROUND: Sarcopenic Obesity is the co-existence of increased adipose tissue (obesity) and decreased muscle mass or strength (sarcopenia) and is associated with worse outcomes than obesity alone. The new EASO/ESPEN consensus provides a framework to standardize its definition. This study sought to evaluate whether there are preliminary differences observed in weight loss or physical function in older adults with and without sarcopenic obesity taking part in a multicomponent weight loss intervention using these new definitions. METHODS: A 6-month, non-randomized, non-blinded, single-arm pilot study was conducted from 2018 to 2020 in adults ≥ 65 years with a body mass index (BMI) ≥ 30 kg/m2. Weekly dietitian visits and twice-weekly physical therapist-led exercise classes were delivered using telemedicine. We conducted a secondary retrospective analysis of the parent study (n = 53 enrolled, n = 44 completers) that investigated the feasibility of a technology-based weight management intervention in rural older adults with obesity. Herein, we applied five definitions of sarcopenic obesity (outlined in the consensus) to ascertain whether the response to the intervention differed among those with and without sarcopenic obesity. Primary outcomes evaluated included weight loss and physical function (30-s sit-to-stand). RESULTS: In the parent study, mean weight loss was - 4.6 kg (95% CI - 3.6, - 5.6; p < 0.001). Physical function measures of 30-s sit-to-stand showed a mean increase of 3.1 in sit-to-stand repetitions (+ 1.9, + 4.3; p < 0.001). In this current analysis, there was a significant decrease in weight and an increase in repetitions between baseline and follow-up within each group of individuals with and without sarcopenia for each of the proposed definitions. However, we did not observe any significant differences in the changes between groups from baseline to follow-up. CONCLUSIONS: The potential lack of significant differences in weight loss or physical function between older adults with and without sarcopenic obesity participating in a weight loss intervention may suggest that well-designed, multicomponent interventions can lead to similar outcomes irrespective of sarcopenia status in persons with obesity. Fully powered randomized clinical trials are critically needed to confirm these preliminary results.

Association Between Mid-arm Muscle Circumference and Cognitive Function: A Longitudinal Study of Chinese Adults.

BACKGROUND: Dementia affects 55 million people worldwide and low muscle mass may be associated with cognitive decline. Mid-arm muscle circumference (MAMC) correlates with dual-energy Xray absorptiometry and bioelectrical impedance analyses, yet are not routinely available. Therefore, we examined the association between MAMC and cognitive performance in older adults. METHODS: We included community-dwelling adults ≥55 years from the China Health and Nutrition Survey. Cognitive function was estimated based on a subset of the modified Telephone Interview for Cognitive Status (0-27, low-high) during years (1991, 1993, 1997, 2000, 2004, 2006, 2009, 2011, 2015, 2018). A multivariable linear mixed-effects model was used to test whether MAMC was associated with rate of cognitive decline across age groups and cognitive function overall. RESULTS: Of 3702 adults (53% female, 63.2 ± 7.3 years), mean MAMC was 21.4 cm ± 3.0 and baseline cognitive score was 13.6 points ±6.6. We found no evidence that the age-related rate of cognitive decline differed by MAMC (P = .77). Declines between 5-year age groups ranged from -.80 [SE (standard error) .18] to -1.09 [.22] for those at a mean MAMC, as compared to -.86 [.25] to -1.24 [.31] for those at a 1 MAMC 1 standard deviation above the mean. Higher MAMC was associated with better cognitive function with .13 [.06] higher scores for each corresponding 1 standard deviation increase in MAMC across all ages. CONCLUSION: Higher MAMC at any age was associated with better cognitive performance in older adults. Understanding the relationship between muscle mass and cognition may identify at-risk subgroups needing targeted interventions to preserve cognition.

Changes in Weight or Body Composition by Frailty Status: A Pilot Study.

Weight loss may benefit older adults with obesity. However, it is unknown whether individuals with different frailty phenotypes have different outcomes following weight loss. Community-dwelling adults aged ≥65 (n = 53) with a body mass index ≥30 kg/m2 were recruited for a six-month, single-arm, technology-based weight loss study. A 45-item frailty index identified frailty status using subjective and objective measures from a baseline geriatric assessment. At baseline, n = 22 participants were classified as pre-frail (41.5%) and n = 31 were frail (58.5%), with no differences in demographic characteristics. While weight decreased significantly in both groups (pre-frail: 90.8 ± 2.7 kg to 85.5 ± 2.4 kg (p < 0.001); frail: 102.7 ± 3.4 kg to 98.5 ± 3.3 kg (p < 0.001), no differences were observed between groups for changes in weight (p = 0.30), appendicular lean mass/height2 (p = 0.47), or fat-free mass (p = 0.06). Older adults with obesity can safely lose weight irrespective of frailty status using a technology-based approach. Further investigation is needed to determine whether the impact of specific lifestyle interventions differ by frailty status.

Nutrition interventions for body composition, physical function, cognition in hospitalized older adults: A systematic review of individuals 75 years and older.

BACKGROUND: Globally, the oldest old population is expected to triple by 2050. Hospitalization and malnutrition can result in progressive functional decline in older adults. Minimizing the impact of hospitalization on functional status in older adults has the potential to maintain independence, reduce health and social care costs, and maximize years in a healthy state. This study aimed to systematically review the literature to identify nutritional interventions that target physical function, body composition, and cognition in the older population (≥ 75 years). METHODS: A systematic review was conducted to evaluate the efficacy of nutritional interventions on physical function, body composition, and cognition in adults aged ≥ 75 years or mean age ≥80 years. Searches of PubMed (National Institutes of Health, National Library of Medicine), Scopus (Elsevier), EMBASE (Elsevier), Cumulative Index to Nursing and Allied Health Literature (CINAHL) with Full Text (EBSCOhost), and PsycInfo (EBSCOhost) were conducted. Screening, data extraction, and quality assessment were performed in duplicate and independently (CRD42022355984; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=355984). RESULTS: Of 8311 citations identified, 2939 duplicates were excluded. From 5372 citations, 189 articles underwent full-text review leaving a total of 12 studies for inclusion. Interventions were food-based, protein-based, carbohydrate-based, personalized, or used parenteral nutrition. Ten studies monitored anthropometric or body composition changes with three showing maintenance or improvements in lean mass, body mass index, triceps skinfold, and mid-upper arm circumference compared with the control group. Six studies monitored physical function but only the largest study found a beneficial effect on activities of daily living. Two of three studies showed the beneficial effects of nutritional intervention on cognition. CONCLUSION: There are few, high-quality, nutrition-based interventions in older adults ≥75 years. Despite heterogeneity, our findings suggest that large, longer-term (>2 weeks) nutritional interventions have the potential to maintain body composition, physical function, and cognition in adults aged 75 years and older during hospitalization.

Using Voice Assistant Systems to Improve Dietary Recall among Older Adults: Perspectives of Registered Dietitians.

Dietary assessments are important clinical tools used by Registered Dietitians (RDs). Current methods pose barriers to accurately assess the nutritional intake of older adults due to age-related increases in risk for cognitive decline and more complex health histories. Our qualitative study explored whether implementing Voice assistant systems (VAS) could improve current dietary recall from the perspective of 20 RDs. RDs believed the implementing VAS in dietary assessments of older adults could potentially improve patient accuracy in reporting food intake, recalling portion sizes, and increasing patient-provider efficiency during clinic visits. RDs reported that low technology literacy in older adults could be a barrier to implementation. Our study provides a better understanding of how VAS can better meet the needs of both older adults and RDs in managing and assessing dietary intake.

Protein Supplementation May Dampen Positive Effects of Exercise on Glucose Homeostasis: A Pilot Weight Loss Intervention.

BACKGROUND: The role of protein in glucose homeostasis has demonstrated conflicting results. However, little research exists on its impact following weight loss. This study examined the impact of protein supplementation on glucose homeostasis in older adults >65 years with obesity seeking to lose weight. METHODS: A 12-week, nonrandomized, parallel group intervention of protein (PG) and nonprotein (NPG) arms for 28 older rural adults (body mass index (BMI) ≥ 30 kg/m2) was conducted at a community aging center. Both groups received twice weekly physical therapist-led group strength training classes. The PG consumed a whey protein supplement three times per week, post-strength training. Primary outcomes included pre/post-fasting glucose, insulin, inflammatory markers, and homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Mean age and baseline BMI were 72.9 ± 4.4 years and 37.6 ± 6.9 kg/m2 in the PG and 73.0 ± 6.3 and 36.6 ± 5.5 kg/m2 in the NPG, respectively. Mean weight loss was -3.45 ± 2.86 kg in the PG and -5.79 ± 3.08 kg in the NPG (p < 0.001). There was a smaller decrease in pre- vs. post-fasting glucose levels (PG: -4 mg ± 13.9 vs. NPG: -12.2 ± 25.8 mg/dL; p = 0.10), insulin (-7.92 ± 28.08 vs. -46.7 ± 60.8 pmol/L; p = 0.01), and HOMA-IR (-0.18 ± 0.64 vs. -1.08 ± 1.50; p = 0.02) in the PG compared to the NPG. CONCLUSIONS: Protein supplementation during weight loss demonstrated a smaller decrease in insulin resistance compared to the NPG, suggesting protein may potentially mitigate beneficial effects of exercise on glucose homeostasis.

Obesity, multiple chronic conditions, and the relationship with physical function: Data from the national health and aging trends survey.

BACKGROUND: The population of older adults living with multiple chronic conditions (MCC) continues to grow. MCC is independently associated with functional limitation and obesity. The aim of our study was to evaluate the association between obesity and MCC, and secondarily, the combined presence of obesity and functional limitations with MCC. METHODS: We analyzed cross-sectional survey data from the National Health and Aging Trends Survey (NHATS) 2011 baseline data, a nationally representative Medicare beneficiary cohort of adults in the United States. We evaluated the coexistent prevalence of obesity and MCC overall, and by standard body mass index (BMI) categories. We then evaluated the prevalence of functional limitations (mobility, self-care, and household activities) and Fried-defined frailty status in persons with a BMI ≥ 30 kg/m2. Logistic regression was used to measure the association between MCC and BMI, and functional limitations and MCC among those with obesity. RESULTS: In the 6,600 participants, the prevalence of concurrent obesity and MCC was 30.4%. Of those with obesity, the prevalence of MCC was 84.0%, and were more likely to have MCC (adjusted OR: 2.17, 95% CI 1.86, 2.54) compared to a normal BMI. Obesity and functional limitations or frailty were more likely have MCC than individuals with obesity alone. CONCLUSIONS: We found that individuals with obesity is strongly associated with MCC and that functional limitations and frailty status have a greater association with having MCC than individuals with obesity without MCC. Future longitudinal analyses are needed to ascertain this relationship.

Association Between Weight Status and Rate of Cognitive Decline: China Health and Nutrition Survey 1997-2018.

BACKGROUND: There is a close relationship between weight status and cognitive impairment in older adults. This study examined the association between weight status and the trajectory of cognitive decline over time in a population-based cohort of older adults in China. METHODS: We used data from adults aged ≥55 years participating in the China health and nutrition survey (1997-2018). Underweight (body mass index [BMI] ≤ 18.5 kg/m2), normal weight (18.5-23 kg/m2), overweight (23-27.5 kg/m2), and obesity (BMI ≥ 27.5 kg/m2) were defined using the World Health Organization Asian cutpoints. Global cognition was estimated every 2-4 years through a face-to-face interview using a modified telephone interview for cognitive status (scores 0-27). The association between BMI and the rate of global cognitive decline, using a restricted cubic spline for age and age category, was examined with linear mixed-effects models accounting for correlation within communities and individuals. RESULTS: We included 5 992 adults (53% female participants, mean age of 62 at baseline). We found differences in the adjusted rate of global cognitive decline by weight status (p = .01 in the cubic spline model). Models were adjusted for sex, marital status, current employment status, income, region, urbanization, education status, birth cohort, leisure activity, smoking status, and self-reported diagnosis of hypertension, diabetes, or Myocardial Infarction (MI)/stroke. In addition, significant declines by age in global cognitive function were found for all weight status categories except individuals with obesity. CONCLUSIONS: In a cohort of adults in China, cognitive decline trajectory differed by weight status. A slower rate of change was observed in participants classified as having obesity.

Feasibility of using the Automated Self-Administered 24-hour (ASA-24) dietary assessment tool in older adults.

Background: Dietary patterns can impact the trajectories of healthy aging. However, dietary assessment tools can be challenging to use. With the increased use of technology in older adults, we aimed to evaluate the feasibility of older adults completing the online, Automated Self-Administered 24-h (ASA-24) dietary assessment tool. Methods: We conducted a randomized, two-period, two-sequence, crossover design of twenty community-dwelling older adults (≥65 years) comparing their preference for completing the ASA-24 alone versus with a research assistant (RA). Participants were recruited via ResearchMatch.com and randomly allocated 1:1 to a sequence of completing both an ASA-24 alone or with an RA, separated by one week. After each session, participants completed an online 11-item feasibility survey (Likert-scale range of 1-5, strongly disagree to strongly agree). Mean and standard deviations were reported for each question. Results: Mean age was 69 ± 3.5 years (90% females), with no differences were observed for sex, age, race, ethnicity, education, or income. Neither group felt a need for RA assistance (p = 0.34). However, both groups felt the system was easier to follow with the help of an RA (RA: 4.4 ± 1.3, vs. SA 4.6 ± 0.5, p = 0.65), particularly when they completed the ASA-24 alone, first (p = 0.04). When conducting the ASA-24 alone, there was less confidence the system could be learned quickly (SA 4.5 ± 0.5→3.4 ± 1.0 vs RA 3.4 ± 1.0→3.4 ± 0.7, p = 0.001). The ASA-24 was thought to be less cumbersome after repeated exposure in those concluding with the RA. Conclusion: While older adults were able to complete the ASA-24 independently, the use of an RA led to improved confidence. Enhancing the sample diversity in a larger number of participants could provide helpful data to improve the science of dietary assessment.

Baseline Serum Biomarkers Predict Response to a Weight Loss Intervention in Older Adults with Obesity: A Pilot Study.

Caloric restriction and aerobic and resistance exercise are safe and effective lifestyle interventions for achieving weight loss in the obese older population (>65 years) and may improve physical function and quality of life. However, individual responses are heterogeneous. Our goal was to explore the use of untargeted metabolomics to identify metabolic phenotypes associated with achieving weight loss after a multi-component weight loss intervention. Forty-two older adults with obesity (body mass index, BMI, ≥30 kg/m2) participated in a six-month telehealth-based weight loss intervention. Each received weekly dietitian visits and twice-weekly physical therapist-led group strength training classes with a prescription for aerobic exercise. We categorized responders' weight loss using a 5% loss of initial body weight as a cutoff. Baseline serum samples were analyzed to determine the variable importance to the projection (VIP) of signals that differentiated the responder status of metabolic profiles. Pathway enrichment analysis was conducted in Metaboanalyst. Baseline data did not differ significantly. Weight loss was 7.2 ± 2.5 kg for the 22 responders, and 2.0 ± 2.0 kg for the 20 non-responders. Mummichog pathway enrichment analysis revealed that perturbations were most significant for caffeine and caffeine-related metabolism (p = 0.00028). Caffeine and related metabolites, which were all increased in responders, included 1,3,7-trimethylxanthine (VIP = 2.0, p = 0.033, fold change (FC) = 1.9), theophylline (VIP = 2.0, p = 0.024, FC = 1.8), paraxanthine (VIP = 2.0, p = 0.028, FC = 1.8), 1-methylxanthine (VIP = 1.9, p = 0.023, FC = 2.2), 5-acetylamino-6-amino-3-methyluracil (VIP = 2.2, p = 0.025, FC = 2.2), 1,3-dimethyl uric acid (VIP = 2.1, p = 0.023, FC = 2.3), and 1,7-dimethyl uric acid (VIP = 2.0, p = 0.035, FC = 2.2). Increased levels of phytochemicals and microbiome-related metabolites were also found in responders compared to non-responders. In this pilot weight loss intervention, older adults with obesity and evidence of significant enrichment for caffeine metabolism were more likely to achieve ≥5% weight loss. Further studies are needed to examine these associations in prospective cohorts and larger randomized trials.

Establishing and sustaining an acute care for elders unit: An incremental journey to success.

Acute Care for Elders (ACE) units reduce hospital-associated delirium, functional decline, and lengths of stay. However, establishing and sustaining such units have proven difficult. There are only 43 ACE units among the >3500 hospitals in the United States. This study describes an iterative quality improvement process, which allowed us to establish and sustain an ACE unit care model in a modern academic hospital. This continuous process was centered on implementing the key principles of the ACE unit model of care: patient-centered care assessments, medical care review, specialized prepared environment, early mobilization, physical therapy, and early planning for discharge to home. Quality of care and patient outcomes data for older adults admitted to our ACE unit includes mortality index (observed/expected) consistently <1 (FY22 = 0.86), 30-day readmission rate of <10% (FY22 9.31%), and length of stay index of ~1 (FY22 1.07). We describe how work on our ACE unit has led to hospital-wide initiatives, including dementia-friendly hospital certification. Our hope is that others can use this process to enhance the dissemination of the ACE unit model of care.

The promise of 4-1BB (CD137)-mediated immunomodulation and the immunotherapy of cancer.

The continuing efforts in biomedical research to develop new therapies for cancer are entering an exciting new phase. Research over the past two to three decades has yielded a much more detailed understanding of the complexities of the cellular and molecular interactions involved in the generation and regulation of immune responses. We are also gaining insights into the mechanisms by which tumors evade or escape immune recognition and by which they become resistant to various existing chemotherapeutic and/or radiotherapeutic strategies. A clear conclusion that can be drawn from these studies is that effective treatments of cancer will become much more multifaceted and will include immunotherapeutic approaches. The identification and molecular cloning of genes encoding the receptors and ligands that play crucial roles in the generation and regulation of immune responses provides exciting new opportunities to induce and enhance effective endogenous immune responses to cancer. In this regard, the genes that comprise the tumor necrosis factor and tumor necrosis factor receptor superfamilies show particular promise. One receptor:ligand pair (4-1BB/CD137 and 4-1BBL/CD137L) is emerging as a target with important potential in its ability to enhance the generation of effective tumor-specific immune responses in situ. The results of the studies cited in this review highlight the potentials of 4-1BB-mediated immunotherapy.

The relationship between multimorbidity, obesity and functional impairment in older adults.

BACKGROUND: Declining mortality rates and an aging population have contributed to increasing rates of multimorbidity (MM) in the United States. MM is strongly associated with a decline in physical function. Obesity is an important risk factor for the development of MM, and its prevalence continues to rise. Our study aimed to evaluate the associations between obesity, MM, and rates of functional limitations in older adults. METHODS: We analyzed body mass index (BMI) and self-reported comorbidity data from 7261 individuals aged ≥60 years from the National Health and Nutrition Examination Surveys 2005-2014. Weight status was defined based on standard BMI categories. MM was defined as 2 or more comorbidities, while functional limitations were self-reported. Adjusted logistic regression quantified the association between standard BMI categories and MM. We also examined the difference in the prevalence of limitations between those with and without MM. RESULTS: The overall proportion of individuals with concomitant MM and obesity was 27.0%. Compared to a normal BMI, older adults with obesity had higher odds of MM (Prevalence odds ratio 1.79, 95% CI 1.49, 2.12). Overall, 67.5% of patients with MM also reported a functional limitation, with rates of functional limitation increasing with increasing BMI. When evaluating functional limitations in those with MM by BMI class, 90% of patients classified as severely obese (BMI ≥40 kg/m2 ) with MM also had a concomitant functional limitation. CONCLUSIONS: Compared to normal weight status, obesity is associated with an increased burden of MM and functional limitation among older adults. Our results underscore the importance of identifying and addressing obesity, MM, and functional limitation patterns and the need for evidence-based interventions that address all three conditions in this population.

Association between food insecurity and probable sarcopenia: Data from the 2011-2014 National Health and nutrition examination survey.

BACKGROUND: Aging alters biological processes resulting in body fat redistribution, loss of lean muscle mass, and reduced muscle strength, termed sarcopenia. Nutrition is an important modifiable risk factor in the development of sarcopenia. Food insecurity refers to limited or uncertain access to enough food for an active, healthy life, and is prevalent among older adults. The objective of this study was to examine the relationship between food insecurity and probable sarcopenia in older adults. METHODS: We examined 3632 adults ≥60 years old from the 2011-2014 National Health and Nutrition Examination Surveys (NHANES). For our analysis food insecurity was identified using the Food Security Survey Module (FSSM). The primary outcome was based on the Sarcopenia Definitions and Outcomes consortium (SDOC) definition. Secondary outcomes were based on three other different grip strength cut-offs as there is debate within the field as to the optimal definition of sarcopenia. Consistent with the revised European consensus on the definition and diagnosis of Sarcopenia (EWGSOP2) recommendations, we used the term probable sarcopenia throughout this text as definitions were based on muscle strength alone and did not include an evaluation of muscle quality. Sensitivity analyses were performed using the standard four category definition of food security. We used logistic regression to examine the association between food insecurity and sarcopenia. RESULTS: Using the Sarcopenia Definitions and Outcomes Consortium definition, 24.7% were classified as having probable sarcopenia (low grip strength); 5.5% had food insecurity and food insecurity was associated with probable sarcopenia (OR 1.51, 95%CI 1.03-2.22). Using three other definitions of probable sarcopenia, food insecurity was significantly associated with probable sarcopenia using the Foundation for the National Institute of Health definition using grip strength alone (OR 1.71, 95%CI 1.08-2.71), but food insecurity was not associated with food insecurity using definitions related to grip strength/BMI (OR 1.16, 95%CI 0.76-1.78) or grip strength/weight (OR 1.14, 95%CI 0.85-1.54). CONCLUSIONS: In this nationally representative cohort study, individuals classified as having food insecurity were more likely to have probable sarcopenia (low grip strength) compared to those with full food security. Future studies should examine whether food insecurity interventions may reduce probable sarcopenia and associated adverse outcomes.

Multimodal Diagnostic Approaches to Advance Precision Medicine in Sarcopenia and Frailty.

Sarcopenia, defined as the loss of muscle mass, strength, and function with aging, is a geriatric syndrome with important implications for patients and healthcare systems. Sarcopenia increases the risk of clinical decompensation when faced with physiological stressors and increases vulnerability, termed frailty. Sarcopenia develops due to inflammatory, hormonal, and myocellular changes in response to physiological and pathological aging, which promote progressive gains in fat mass and loss of lean mass and muscle strength. Progression of these pathophysiological changes can lead to sarcopenic obesity and physical frailty. These syndromes independently increase the risk of adverse patient outcomes including hospitalizations, long-term care placement, mortality, and decreased quality of life. This risk increases substantially when these syndromes co-exist. While there is evidence suggesting that the progression of sarcopenia, sarcopenic obesity, and frailty can be slowed or reversed, the adoption of broad-based screening or interventions has been slow to implement. Factors contributing to slow implementation include the lack of cost-effective, timely bedside diagnostics and interventions that target fundamental biological processes. This paper describes how clinical, radiographic, and biological data can be used to evaluate older adults with sarcopenia and sarcopenic obesity and to further the understanding of the mechanisms leading to declines in physical function and frailty.

Inhibition of adenine nucleotide translocator pore function and protection against apoptosis in vivo by an HIV protease inhibitor.

Inhibitors of HIV protease have been shown to have antiapoptotic effects in vitro, yet whether these effects are seen in vivo remains controversial. In this study, we have evaluated the impact of the HIV protease inhibitor (PI) nelfinavir, boosted with ritonavir, in models of nonviral disease associated with excessive apoptosis. In mice with Fas-induced fatal hepatitis, Staphylococcal enterotoxin B-induced shock, and middle cerebral artery occlusion-induced stroke, we demonstrate that PIs significantly reduce apoptosis and improve histology, function, and/or behavioral recovery in each of these models. Further, we demonstrate that both in vitro and in vivo, PIs block apoptosis through the preservation of mitochondrial integrity and that in vitro PIs act to prevent pore function of the adenine nucleotide translocator (ANT) subunit of the mitochondrial permeability transition pore complex.