International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines.

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.

A Systematic Review of Clinical Practice Guidelines for Identification and Management of Frailty.

OBJECTIVE: This study aims to appraise and summarize consistent recommendations from clinical practice guidelines (CPGs) for identification and management of frailty to maintain and improve functional independence of elderly population. METHODS: A systematic search of Ovid MEDLINE, Embase, PubMed, PsycINFO, and CINAHL electronic databases using database-specific search terms in two broad areas "guidelines" and "frailty", and a manual search of websites with the key phrase "frailty guideline" was performed. The inclusion criteria included CPGs focusing on identifying and managing frailty in population >65 years old, published in English since January 2010. Three reviewers independently assessed guideline quality using the AGREE II instrument. Data extraction was performed, followed by compilation and comparison of all recommendations to identify the key consistent recommendations. RESULTS: Six CPGs met the inclusion criteria; however, only three CPGs had high methodological quality in accordance with AGREE II appraisal. The average AGREE II scores of all six CPGs were: 84.5%, 68%, 46.5%, 81.5%, 56.3%, and 60.2% for domains 1-6 (scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability, and editorial independence) respectively. A total of 54 recommendations were identified, with 12 key recommendations suggested frequently by the CPGs. CONCLUSION: The AGREE II instrument identified strengths and weaknesses of the CPGs, but failed to assess clinical implications and feasibility of the guidelines. Further research is needed to improve clinical relevance of CPGs in the identification and management of frailty. The feasibility in implementing these guidelines with regards to cost-effectiveness of frailty screening warrants further investigation.

Sex-specific muscle and metabolic biomarkers associated with gait speed and cognitive transitions in older adults: a 9-year follow-up.

Physical frailty and cognitive frailty share biological mechanisms, but sex-specific biomarkers associated with transitions in gait speed and cognition during ageing are poorly understood.Gait speed, cognition (3MSE), body composition (DXA) and serological biomarkers were assessed annually over 9 years in 216 males (72.7 + 8.07 years) and 384 females (71.1 + 8.44 years). In females, maintaining normal gait speed was associated with lower percent body fat (IRR 0.793, p = 0.001, 95%CI 0.691-0.910) and lower lactate dehydrogenase (LDH) (IRR 0.623, p = 0.00, 95%CI 0.514-0.752), and in males, the association was with higher cholesterol (IRR 1.394, p = 0.001, 95%CI 1.154-1.684). Abnormal to normal gait speed transitions were associated with higher insulin in females (IRR 1.325, p = 0.022, 95%CI 1.041-1.685) and lower creatinine in males (IRR 0.520, p = 0.01, 95%CI 0.310-0.870). Normal to slow gait speed transitions in males were associated with IGF-1 (IRR 1.74, p = 0.022, 95%CI 1.08-2.79) and leptin in females (IRR 1.39, p = 0.043, 95%CI 1.01-1.91.) Maintaining normal cognition was associated with lower LDH in females (IRR 0.276, p = 0.013, 95%CI 0.099-0.765) and higher appendicular skeletal muscle mass in males (IRR 1.52, p = 0.02, 95%CI 1.076-2.135). Improved cognition was associated with higher leptin (IRR 7.5, p = 0.03, 95%CI 1.282-44.34) and lower triglyceride (IRR 0.299, p = 0.017, 95%CI 0.110-0.809) in males. Education was protective against cognitive decline in females (IRR 0.84, p = 0.037, 0.732-0.982). Sex-specific biomarkers of muscle (LDH, Creatinine, IGF-1, APSM) and metabolism (%fat, insulin,cholesterol, leptin, tryglycerides) were associated with gait speed and cognitive transitions. These data suggest that modifiable biomarkers of muscle and metabolism could be targeted for interventions.

Physical Frailty: ICFSR International Clinical Practice Guidelines for Identification and Management.

OBJECTIVE: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. METHODS: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care. Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation). Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.

Relationship of Incident Falls with Balance Deficits and Body Composition in Male and Female Community-Dwelling Elders.

OBJECTIVE: Sarcopenia and obesity are reported risk factors for falls, although the data are not consistent and most studies do not make sex comparisons. We investigated whether falls were associated with balance, gait, and body composition, and whether these relationships are sex-specific. DESIGN: Secondary analysis of 4-year follow-up data from of the New Mexico Aging Process Study. SETTING: Albuquerque, New Mexico. PARTICIPANTS: 307 participants (M, n=122, 75.8 yr. SD5.5; F, n=183, 74.6yr SD6.1). MEASUREMENTS: Gait and balance were assessed annually using the Tinetti test. Lean body mass (LBM), appendicular skeletal muscle mass (ASM), fat free mass (FFM), total fat mass (FM) were assessed annually by DXA. Falls were assessed using bimonthly falls calendars. Hazard ratios (HR) for 2-point worsening in gait and balance score and falls were calculated by Cox proportional hazard for men and women. RESULTS: Baseline balance deficits, and not body composition, represented the strongest predictor of falls. For the total balance score, the variables with significant sex interactions were ASM (Male-HR 1.02 95%CI 0.60-1.73; Female-HR 1.92 95%CI 1.05-3.52, p=0.03) and FFM (Male-HR 1.04 95%CI 0.64-1.70; Female-HR 1.91 95%CI 1.12-3.24, p=0.04), after adjustment for age, sarcopenia and physical activity. The body composition relationship with balance deficits was U-shaped with the strongest predictors being low LBM in males and high FM in females. CONCLUSIONS: Specific body composition components and balance deficits are risk factors for falls following sex-specific patterns. Sex differences need to be explored and considered in interventions for worsening balance and falls prevention.

Establishing an Operational Definition of Sarcopenia in Australia and New Zealand: Delphi Method Based Consensus Statement.

BACKGROUND: Globally there are several operational definitions for sarcopenia, complicating clinical and research applications. OBJECTIVE: The objective of the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Task Force on Diagnostic Criteria for Sarcopenia was to reach consensus on the operational definition of sarcopenia for regional use by clinicians and researchers. METHOD: A four-Phase modified Delphi process was undertaken in which 24 individuals with expertise or a recognised interest in sarcopenia from different fields across Australia and New Zealand were invited to be Task Force members. An initial face-to-face meeting was held in Adelaide, South Australia, in November 2017, followed by two subsequent online Phases conducted by electronic surveys. A final Phase was used to approve the final statements. Responses were analysed using a pre-specified strategy. The level of agreement required for consensus was 80%. RESULTS: In Phase 2, 94.1% of Task Force respondents voted in favour of adopting an existing operational definition of sarcopenia. In Phase 3, 94.4% of respondents voted in favour of adopting the European Working Group on Sarcopenia in Older People (EWGSOP) definition as the operational definition for sarcopenia in Australia and New Zealand. CONCLUSION: With consensus achieved, the ANZSSFR will adopt, promote and validate the EWGSOP operational definition of sarcopenia for use by clinicians and researchers in Australia and New Zealand.

International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management.

OBJECTIVES: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR). METHODS: To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefit-harm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process. RECOMMENDATIONS: We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.

Designing Drug Trials for Frailty: ICFSR Task Force 2018.

To reduce disability and dependence in older adults, frailty may represent an appropriate target for intervention. While preventing frailty through lifestyle interventions may be the optimal public health approach for many population groups, pharmacological approaches will likely be needed for individuals who meet frailty criteria or who have comorbid conditions that contribute to and complicate the frailty syndrome, and for those who are not compliant with lifestyle interventions. Barriers to successful development of drug treatments for frailty include variability in how the frailty syndrome is defined, lack of agreement on the best diagnostic tools and outcome measures, and the paucity of sensitive, reliable, and validated biomarkers. The International Conference on Frailty and Sarcopenia Research Task Force met in Miami, Florida, on February 28, 2018, to consider the status of treatments under development for frailty and discuss potential strategies for advancing the field. They concluded that at the present time, there may be a more productive regulatory pathway for adjuvant treatments or trials targeting specific functional outcomes such as gait speed. They also expressed optimism that several studies currently underway may provide the insight needed to advance drug development for frailty.

Systematic review of the impact of osteoarthritis on health outcomes for comorbid disease in older people.

OBJECTIVE: A systematic review was undertaken examining the impact of comorbid osteoarthritis on health outcomes for people aged 50 years or older with cardiovascular disease, diabetes or obesity. DESIGN: The protocol is registered in PROSPERO (CRD42015023417). Relevant electronic databases and grey literature were systematically searched for studies published in English between January 2005 and December 2016. Two reviewers independently screened studies for selection using predetermined inclusion and exclusion criteria, and independently completed methodological quality review. Data was extracted at study level by one reviewer and independently checked by a second reviewer, using a standardized form. The results across studies were qualitatively synthesized with outcomes described and summarized. RESULTS: Of 1456 articles, we identified 15 relevant studies, with nine good to high quality studies describing significant negative impact of osteoarthritis on outcomes for cardiovascular diseases. There were too few studies focussing on diabetes and obesity to make conclusions in regard to these diseases. CONCLUSIONS: This review provides evidence that osteoarthritis should not be overlooked when impacts of chronic disease on health outcomes and related health service use are considered. There is a clear need for more studies that consider the impacts of osteoarthritis on comorbid disease, especially those that consider the impact of osteoarthritis beyond the morbidity impacts. The management of comorbid osteoarthritis should be addressed for those with cardiovascular disease, and treatment choices considered given this association.

Reversible States of Physical and/or Cognitive Dysfunction: A 9-Year Longitudinal Study.

OBJECTIVES: To determine 1) age-adjusted transition probabilities to worsening physical/cognitive function states, reversal to normal cognition/physical function, or maintenance of normal state; 2) whether these transitions are modulated by sex, BMI, education, hypertension (HTN), health status, or APOE4; 3) whether worsening gait speed preceded cognition change, or vice versa. DESIGN: Analysis of 9-year prospective cohort data from the New Mexico Aging Process Study. SETTING: Healthy independent-living adults. PARTICIPANTS: 60+ years of age (n= 598). MEASUREMENTS: Gait speed, cognitive function (3MSE score), APOE4, HTN, BMI, education, health status. RESULTS: Over 9 years, 2129 one-year transitions were observed. 32.6% stayed in the same state, while gait speed and cognitive function (3MSE scores) improved for 38% and 43% of participants per year, respectively. Transitions to improved function decreased with age (P< 0.001), APOE4 status (P=0.02), BMI (P=0.009), and health status (P=0.009). Transitions to worse function were significantly increased for the same factors (all P<0.05). Times to lower gait speed and cognitive function did not precede each other (P=0.91). CONCLUSIONS: Transitions in gait speed and cognition were mutable with substantial likelihood of transition to improvement in physical and cognitive function even in oldest-old, which may have clinical implications for treatment interventions.

Arbuscular mycorrhizal fungi: effects on plant terpenoid accumulation.

Arbuscular mycorrhizal fungi (AMF) are a diverse group of soil-dwelling fungi that form symbiotic associations with land plants. AMF-plant associations promote the accumulation of plant terpenoids beneficial to human health, although how AMF mediate terpenoid accumulation is not fully understood. A critical assessment and discussion of the literature relating to mechanisms by which AMF influence plant terpenoid accumulation, and whether this symbiosis can be harnessed in horticultural ecosystems was performed. Modification of plant morphology, phosphorus availability and gene transcription involved with terpenoid biosynthetic pathways were identified as key mechanisms associated with terpenoid accumulation in AMF-colonised plants. In order to exploit AMF-plant symbioses in horticultural ecosystems it is important to consider the specificity of the AMF-plant association, the predominant factor affecting terpenoid accumulation, as well as the end use application of the harvested plant material. Future research should focus on resolving the relationship between ecologically matched AMF genotypes and terpenoid accumulation in plants to establish if these associations are effective in promoting mechanisms favourable for plant terpenoid accumulation.

Sexually dimorphic patterns of nutritional intake and eating behaviors in community-dwelling older adults with normal and slow gait speed.

OBJECTIVES: Assess sex-specific nutritional intake and dietary habits of independently living older adults with normal and slow gait speeds. DESIGN: New Mexico Aging Process Study, cross-sectional, secondary data analysis. SETTING: Albuquerque, New Mexico USA. PARTICIPANTS: Three-hundred fifteen adults 60 years and older (194 women and 121 men). MEASUREMENTS: Gait speed test, 3-day diet records, Mini-Mental State Examination, and body mass index. RESULTS: Slow gait speed was associated with lower total calories (-154 kcal/day) and zinc (1 mg/day) (.05 < p < .1). Slower men consumed less protein (-4.1 g/day), calcium (-140 mg), fiber (-2.8 g/day) and iron (-2.5 mg/day) (p≤.05). Slower women consumed less, protein (-5.5 g/day), carbohydrate (-19.1 g/day), fiber (-2.7 gm/day), vitamin C (-18.4 mg/day) and higher fat intake (p=0.03). Slower women snacked less, had trouble chewing/biting, and lived alone (p= .04). Slower men were less likely to snack. CONCLUSIONS: We found sex-specific nutritional differences associated with gait speed. Those presenting with slow gait speed may need encouragement to increase meat and whole grain breads/cereal. Those with trouble eating should be advised on adapting diet to maintain adequate nutrition and encouraged on regular snacking to achieve higher nutrient intake. Prospective and randomized controlled studies are needed to confirm these findings and provide further evidence for putting these suggestions into practice.

Long-term maintenance of weight loss after lifestyle intervention in frail, obese older adults.

OBJECTIVES: To determine if long-term weight loss with associated improvement in physical and metabolic health can be maintained after lifestyle intervention in frail, obese older adults. DESIGN: Thirty-month follow-up pilot study of a 1-year lifestyle intervention trial. SETTING: Community. PARTICIPANTS: Sixteen frail, obese (body mass index=36±2 kg/m2) older (71±1 yr.) adults. MEASUREMENTS: Body weight and composition, physical function, markers of the metabolic syndrome, glucose and insulin response to an oral glucose tolerance test, bone mineral density (BMD), liver and renal function tests, and food diaries. RESULTS: At 30-month follow-up, weight (101.5±3.8 vs. 94.5±3.9 kg) and BMI (36.0 ±1.7 vs. 33.5±1.7 kg/m2) remained significantly below baseline (all p<0.05). No significant change in fat-free mass (56.7±2.1 vs. 56.9±2.2 kg) or appendicular lean mass (24.1±1.0 vs. 24.1±1.1kg, all p>0.05) occurred between 12 months (end of trial) and 30 months. Improvements in the physical performance test (PPT 27±0.7 vs. 30.2±0.6), insulin sensitivity (4.1±0.8 vs. 3.0±0.6), and insulin area under the curve (12484±2042 vs. 9270±1139 min.mg/dl) remained at 30 months compared to baseline (all p<0.05). Waist circumference (116±3 vs. 109±3 cm) and systolic blood pressure (134±6 vs. 123±5 mm HG) remained decreased at 30 months compared to baseline (all p<0.05). Whole body and lumbar spine BMD did not change; however, total hip BMD progressively decreased at 30 months compared to baseline (0.985±.026 vs. 0.941±.024 g/cm2; p<0.05). There were no adverse effects on liver or renal function. Food frequency questionnaire data showed lower overall caloric intake (-619±157 kcal/day) at 30 months compared to baseline (p<0.05). CONCLUSION: These findings suggest that long-term maintenance of clinically important weight loss is possible in frail, obese older adults. Weight maintenance appears to be achieved through continued caloric restriction. Larger, long-term studies are needed to follow up on these findings and investigate mechanisms and behaviors underlying maintenance of weight loss and physical function.

Gender Specific Associations between Frailty and Body Composition.

BACKGROUND: Frailty is a widespread geriatric syndrome, but its relationship with body composition is largely unknown. OBJECTIVES: Assess the relationship between body composition and frailty in older persons. DESIGN, PARTICIPANTS AND SETTING: Cross-sectional data analyses in 120 community-dwelling older persons (50 men, 70 women, mean age 78.5 ± 6 yr). MEASUREMENTS: Frailty was measured according to Fried's criteria and calculated as a score, and also a binary variable. Anthropometric measures were obtained (height, weight), and body composition (total lean body mass, appendicular skeletal muscle mass (ASM), total fat mass, and percentage fat), assessed by dual energy x-ray absorptiometry. Multiple regression and logistic regression analyses stratified by gender were conducted. RESULTS: Frailty, as a binary measure, was more prevalent in women than men (67.1% vs 46% p=0.04). Prevalence of low muscle mass (ASM/ht2) was higher in men than in women (40.0% vs 32.9%, p=0.04). Using gender-specific percentage fat cut-scores (27% men, 38% women, respectively) obesity was more prevalent in women than men (58.6% vs 34%, respectively, p=0.01). Multiple regression models showed age as an independent associated factor of frailty in men (ß 0.310, p=0.009) and women (ß .581 p<0.001). ASM/ht2 was a significant associated factor in men (ß -0.517, p<0.001) and trended towards significance in women (ß -0.188, p=0.06). Percentage fat was a significant associated factor in women only (ß 0.234, p=0.02). Logistic regression with frailty as a binary dependent variable yielded similar results. CONCLUSION: In this sample of older adults, the significant associated factor of frailty in men was ASM/ht2, whereas it was percentage fat in women. These associations were independent of age. With increasing longevity and the high prevalence of sarcopenia and obesity in older populations, these findings have public health implications. Larger sample and specifically designed studies are needed in order to confirm and extend these findings.

Social Engagement of Frail Elders.

BACKGROUND: Social isolation is a significant problem for frail older adults and the determinants of social engagement are poorly understood. OBJECTIVES: This study explored the social engagement of frail elders to identify personal attributes associated with social engagement. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional sample of seventy-three people receiving home-based care in one town on the South Island of New Zealand (mean age 82 (7.2) yrs, n=51 Females, 21 Males). MEASUREMENTS: Face-to-face semi-structured interviews and questionnaires. Functional independence was measured using Nottingham Extended Activities of Daily Living (EADL), self-efficacy by General Self Efficacy Scale, and 2 open-ended questions were piloted on social activities and helping others. RESULTS: Regression models identified two statistically associated components of social engagement: social activities and civic involvement. Contributions to families and community organizations and exercise were important social activities. Personal attributes included perceived functional independence and self-efficacy. CONCLUSIONS: In frail older adults, a measurement of social engagement should address activities older adults identify as important, including exercise. Independence, self -efficacy, and social engagement may interact in reinforcing cycles of empowerment and could play a role in developing interventions to retain and maintain function in frail older adults.