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Background and Objectives The relationship between frailty and disability in activities of daily living (ADLs) can be seen in different ways, with disability being—to varying degrees—a characteristic, negative outcome, or predictor of frailty. This conflation of definitions is partly a result of the different frailty tools used in research. Aiming to provide a comprehensive overview, this systematic literature search analyzed (i) if, (ii) to what extent, and (iii) how ADLs are evaluated by frailty instruments. Research Design and Methods A search was performed in PubMed, Web of Knowledge, and PsycINFO to identify all frailty instruments, followed by categorization of the ADL items into basic (b-), instrumental (i-), and advanced (a-) ADLs. Results In total, 192 articles described 217 frailty instruments, from which 52.1% contained ADL items: 45.2% b-ADLs, 35.0% i-ADLs, and 10.1% a-ADLs. The most commonly included ADL items were bathing (b-ADLs); using transportation (i-ADLs); and semiprofessional work engagement in organized social life or leisure activities (a-ADLs). These instruments all had a multidomain origin (χ 2 = 122.4, p <.001). Discussion and Implications Because 52.1% of all instruments included ADL items, the concepts of frailty and disability appear to be highly entangled. This might lead to circular reasoning, serious concerns regarding contamination, and invalid research results. [ABSTRACT FROM AUTHOR]

In stroke rehabilitation there is a growing body of evidence that not all patients have the same potential to recover. Understanding the processes that give rise to the heterogeneous treatment responses in stroke survivors will lay foundations for any conceivable advance in future rehabilitation interventions. This review was set out to shine new light on the debate of biomarkers in stroke rehabilitation by linking fundamental insights from biogerontological sciences to neurorehabilitation sciences. In particular, skeletal muscle changes and inflammation are addressed as two potential constructs from which biomarkers for stroke rehabilitation can be derived. Understanding the interplay between these constructs as well as their relation to recovery could enhance stroke rehabilitation in the future. The rationale for the selection of these constructs is three-fold: first, recent stroke literature emphasizes the importance of identifying muscle wasting (also called stroke-induced muscle wasting) in stroke patients, a concept that is widely investigated in geriatrics but less in the stroke population. Second, insights from transdisciplinary research domains such as gerontology have shown that inflammation has severe catabolic effects on muscles, which may impede rehabilitation outcomes such as gait recovery. Last, it has been proven that (high-intensity) muscle strengthening exercises have strong anti-inflammatory effects in a non-stroke population. Therefore, an evidence-based rationale is presented for developing research on individual changes of muscle and inflammation after a stroke. [ABSTRACT FROM AUTHOR]

Abstract Background Low grip strength is recognized as one of the characteristics of frailty, as are systemic inflammation and the sensation of fatigue. Contrary to maximal grip strength, the physical resistance of the muscles to fatigue is not often included in the clinical evaluation of elderly patients. The aim of this study was to investigate if the grip strength and the resistance of the handgrip muscles to fatigue are related to self-perceived fatigue, physical functioning and circulating IL-6 in independently living elderly persons. Methods Forty elderly subjects (15 female and 25 male, mean age 75 ± 5 years) were assessed for maximal grip strength, as well as for fatigue resistance and grip work (respectively time and work delivered until grip strength drops to 50% of its maximum during sustained contraction), self perceived fatigue (VAS-Fatigue, Mob-Tiredness scale and the energy & fatigue items of the WHOQOL-100), self rated physical functioning (domain of physical functioning on the MOS short-form) and circulating IL-6. Relationships between handgrip performance and the other outcome measures were assessed. Results In the male participants, fatigue resistance was negatively related to actual sensation of fatigue (VAS-F, p < .05) and positively to circulating IL-6 (p < .05). When corrected for body weight, the relations of fatigue resistance with self-perceived fatigue became stronger and also apparent in the female. Grip strength and grip work were significantly related with several items of self-perceived fatigue and with physical functioning. These relations became more visible by means of higher correlation coefficients when grip strength and grip work were corrected for body weight. Conclusion Well functioning elderly subjects presenting less handmuscle fatigue resistance and weaker grip strength are more fatigued, experience more tiredness during daily activities and are more bothered by fatigue sensations. Body weight seems to play an important role in the relation of muscle performance to fatigue perception. Elderly patients complaining from fatigue should be physically assessed, both evaluating maximal grip strength and fatigue resistance, allowing the calculation of grip work, which integrates both parameters. Grip work might best reflect the functional capacity resulting from the development of a certain strength level in relation to the time it can be maintained.

Abstract Background Fatigue or lack of interest can reduce the feasibility of intensive physical exercise in nursing home residents. Low-volume exercise interventions with similar training effects might be an alternative. The aim of this randomised controlled trial was to investigate the feasibility of Whole Body Vibration (WBV) in institutionalised elderly, and its impact on functional capacity and muscle performance. Methods Twenty-four nursing home residents (15 female, 9 male; mean age 77.5 ± 11.0 years) were randomised (stratification for age, gender and ADL-category) to 6 weeks static WBV exercise (WBV+, N = 13) or control (only static exercise; N = 11). Outcome measures were exercise compliance, timed up-and-go, Tinetti-test, back scratch, chair sit-and-reach, handgrip strength and linear isokinetic leg extension. Results At baseline, WBV+ and control groups were similar for all outcome variables. Twenty-one participants completed the program and attended respectively 96% and 86% of the exercise sessions for the WBV+ and control groups. Training-induced changes in timed up-and-go and Tinetti-test were better for WBV+ compared to control (p = 0.029 for timed up-and-go, p = 0.001 and p = 0.002 for Tinetti body balance and total score respectively). In an alternative analysis (Worst Rank Score & Last Observation Carried Forward) the differences in change remained significant on the Tinetti body balance and total score. No other significant differences in change between both groups were observed. Conclusion In nursing home residents with limited functional dependency, six weeks static WBV exercise is feasible, and is beneficial for balance and mobility. The supplementary benefit of WBV on muscle performance compared to classic exercise remains to be explored further.

Abstract Background The 6 minutes walk test (6MWT) is a useful assessment instrument for the exercise capacity of elderly persons. The impact of the health status on the 6MWT-distance in elderly, however, remains unclear, reducing its value in clinical settings. The objective of this study was to investigate to what extent the 6MWT-distance in community dwelling elderly is determined by health conditions. Methods One hundred and fifty-six community dwelling elderly people (53 male, 103 female) were assessed for health status and performed the 6MWT. After clinical evaluation, electrocardiography and laboratory examination participants were categorized into a stratified six-level classification system according to their health status, going from A (completely healthy) to D (signs of active disease at the moment of examination). Results The mean 6MWT-distance was 603 m (SD = 178). The 6MWT-distance decreased significantly with increasing age (ANOVA p = 0.0001) and with worsening health status (ANCOVA, corrected for age p < 0.001). A multiple linear regression model with health status, age and gender as independent variables explained 31% of the 6MWT-distance variability. Anthropometrical measures (stature, weight and BMI) did not significantly improve the prediction model. A significant relationship between 6MWT-distance and stature was only present in category A (completely healthy). Conclusions Significant differences in 6MWT-distance are observed according to health status in community-dwelling elderly persons. The proposed health categorizing system for elderly people is able to distinguish persons with lower physical exercise capacity and can be useful when advising physical trainers for seniors.

Aims: Safety and tolerability of prolonged supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink (WP-MND) was evaluated in sarcopenic older adults. Methods: A 13-week double-blinded, randomized, isocaloric placebo-controlled trial (PROVIDE study; n = 380) was extended with a voluntary 13-week open-label extension (OLE). OLE participants were randomized to receive daily 1 or 2 servings of WP-MND (21 g protein, 3 g leucine, 10 µg vitD and 500 mg calcium per serving). Gastro-intestinal tolerability, kidney function and serum levels of calcidiol, parathyroid hormone (PTH) and calcium were evaluated at week 0, 13 and 26. Results and discussion: In response to the high daily protein intake (median1.5; IQR: 1.3, 1.7 g/kg BW/day), the estimated glomerular filtration rate (eGFR) increased in the test group during the RCT (p = 0.013). The same trend was observed for those participants with moderate chronic kidney disease. During OLE no eGFR change was observed in any of the groups. Serum calcidiol and calcium reached a plateau after 13-week WP-MND supplementation. As expected, PTH significantly changed in the opposite direction, decreasing during RCT in the test group (T vs C: p < 0.001) and during OLE in former control groups. During RCT, 20/366 participants with normal baseline calcidiol reached levels ≥ 100 nmol/L (T: n = 18; C: n = 2) and 6 developed albumin-corrected calcium levels > 2.55 mmol/L (T: n = 3; C: n = 3), without associated adverse events. Conclusion: A 6 months intervention with up to 2 servings of WP-MND did neither result in kidney function deterioration nor symptoms of vitamin D or calcium toxicity. The product was overall well tolerated. [ABSTRACT FROM AUTHOR]

Aging is characterized by a progressive decline in immune function known as immunosenescence. Although the causes of immunosenescence are likely to be multifactorial, an age-associated accumulation of senescent T cells and decreased naive T-cell repertoire are key contributors to the phenomenon. On the other hand, there is a growing consensus that physical exercise may improve immune response in aging. However, the optimum training modality required to obtain beneficial adaptations in older subjects is lacking. Therefore, we aimed to investigate the effects of exercise modality on T-cell phenotypes in older women. A total of 100 women (aged ≥ 65 years) were randomized to either intensive strength training (80% of one-repetition maximum ), strength endurance training (40% one-repetition maximum), or control (stretching exercise) for 2-3 times per week during 6 weeks. The T-cell percentages and absolute counts were determined using flow cytometry and a hematology analyzer. C-reactive protein was measured using immunonephelometry. We report for the first time that 6 weeks of strength endurance training significantly decreased the basal percentage and absolute counts of senescence-prone T cells, which was positively related to the number of training sessions performed. Conceivably, training protocols with many repetitions-at a sufficiently high external resistance-might assist the reduction of senescence-prone T cells in older women. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes, a highly prevalent chronic disease, is associated with increasing frailty and functional decline in older people. We aimed to evaluate the effectiveness of a multimodal intervention on functional performance in frail and pre‐frail participants aged ≥70 years with type 2 diabetes mellitus. Methods: The MID‐Frail study was a cluster‐randomized multicenter clinical trial conducted in 74 trial sites across seven European countries. The trial recruited 964 participants who were aged >70 years [mean age in intervention group, 78.4 (SD 5.6) years, 49.2% male and 77.6 (SD 5.29) years, 52.4% male in usual care group], with type diabetes mellitus and determined to be frail or pre‐frail using Fried's frailty phenotype. Participants were allocated by trial site to follow either usual care (UCG) or intervention procedures (IG). Intervention group participants received a multimodal intervention composed of (i) an individualized and progressive resistance exercise programme for 16 weeks; (ii) a structured diabetes and nutritional educational programme over seven sessions; and (iii) Investigator‐linked training to ensure optimal diabetes care. Short Physical Performance Battery (SPPB) scores were used to assess change in functional performance at 12 months between the groups. An analysis of the cost‐effectiveness of the intervention was undertaken using the incremental cost‐effectiveness ratio (ICER). Secondary outcomes included mortality, hospitalization, institutionalization, quality of life, burden on caregivers, the frequency and severity of hypoglycaemia episodes, and the cost‐effectiveness of the intervention. Results: After 12 months, IG participants had mean SPPB scores 0.85 points higher than those in the UCG (95% CI, 0.44 to 1.26, P < 0.0001). Dropouts were higher in frail participants and in the intervention group, but significant differences in SPPB between treatment groups remained consistent after sensitivity analysis. Estimates suggest a mean saving following intervention of 428.02 EUR (2016) per patient per year, with ICER analysis indicating a consistent benefit of the described health care intervention over usual care. No statistically significant differences between groups were detected in any of the other secondary outcomes. Conclusions: We have demonstrated that a 12 month structured multimodal intervention programme across several clinical settings in different European countries leads to a clinically relevant and cost‐effective improvement in the functional status of older frail and pre‐frail participants with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

It is well recognized that poor muscle function and poor physical performance are strong predictors of clinically relevant adverse events in older people. Given the large number of approaches to measure muscle function and physical performance, clinicians often struggle to choose a tool that is appropriate and validated for the population of older people they deal with. In this paper, an overview of different methods available and applicable in clinical settings is proposed. This paper is based on literature reviews performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia. Face-to-face meetings were organized afterwards where the whole group could amend and discuss the recommendations further. Several characteristics should be considered when choosing a tool: (1) purpose of the assessment (intervention, screening, diagnosis); (2) patient characteristics (population, settings, functional ability, etc.); (3) psychometric properties of the tool (test-retest reliability, inter-rater reliability, responsiveness, floor and ceiling effects, etc.); (4) applicability of the tool in clinical settings (overall cost, time required for the examination, level of training, equipment, patient acceptance, etc.); (5) prognostic reliability for relevant clinical outcomes. Based on these criteria and the available evidence, the expert group advises the use of grip strength to measure muscle strength and the use of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice. The tools proposed are relevant for the assessment of muscle weakness and physical performance. Subjects with low values should receive additional diagnostic workups to achieve a full diagnosis of the underlying condition responsible (sarcopenia, frailty or other). [ABSTRACT FROM AUTHOR]

Background: A chronic low-grade inflammatory profile (CLIP) is associated with sarcopenia in older adults. Protein and Vitamin (Vit)D have immune-modulatory potential, but evidence for effects of nutritional supplementation on CLIP is limited. Aim: To investigate whether 13 weeks of nutritional supplementation of VitD and leucine-enriched whey protein affected CLIP in subjects enrolled in the PROVIDE-study, as a secondary analysis. Methods: Sarcopenic adults (low skeletal muscle mass) aged ≥ 65 years with mobility limitations (Short Physical Performance Battery 4–9) and a body mass index of 20–30 kg/m2 were randomly allocated to two daily servings of active (n = 137, including 20 g of whey protein, 3 g of leucine and 800 IU VitD) or isocaloric control product (n = 151) for a double-blind period of 13 weeks. At baseline and after 13 weeks, circulating interleukin (IL)-8, IL-1 receptor antagonist (RA), soluble tumor-necrosis-factor receptor (sTNFR)1, IL-6, high-sensitivity C-reactive protein, pre-albumin and 25-hydroxyvitamin(OH)D were measured. Data-analysis included repeated measures analysis of covariance (corrected for dietary VitD intake) and linear regression. Results: IL-6 and IL-1Ra serum levels showed overall increases after 13 weeks (p = 0.006 and p < 0.001, respectively). For IL-6 a significant time × treatment interaction (p = 0.046) was observed, with no significant change over time in the active group (p = 0.155) compared to control (significant increase p = 0.012). IL-8 showed an overall significant decrease (p = 0.03). The change in pre-albumin was a significant predictor for changes in IL-6 after 13 weeks. Conclusions: We conclude that 13 weeks of nutritional supplementation with VitD and leucine-enriched whey protein may attenuate the progression of CLIP in older sarcopenic persons with mobility limitations. [ABSTRACT FROM AUTHOR]

Frailty is highly prevalent in old age and confers an important mortality risk. Although the causes of frailty are multiple, immunosenescence (IS)-predominantly driven by cytomegalovirus (CMV)-has been implicated in its pathophysiology. Thus far, research examining the association between IS and frailty states is sparse and equivocal. On the other hand, evidence is mounting in support of the view that frailty can be reversed, especially for those in the pre-frail stage. Therefore, we aimed to clarify the impact of CMV on IS and its relevance to pre-frailty. One hundred seventy-three persons aged 80 to 99 years were enrolled. Pre-frailty was defined according to Fried's criteria. Anti-CMV IgG and serum IL-6 were measured using Architect iSystem and Luminex, respectively. T-cell phenotypes were determined using flow cytometry. The prevalence of pre-frailty was 52.6%, increased with age (p = .001), and was greater in men than women (p = .044). No relationship was found between pre-frailty and positive CMV serology. Further, CMV-seropositivity was significantly associated with less naïve cells, more memory and senescence-prone phenotypes (all p < .001). After adjusting for potential confounders, only IL-6, age and sex were predictive of pre-frailty. We conclude that the presence of pre-frailty is independent from CMV infection in very old subjects. [ABSTRACT FROM AUTHOR]