The LEISURE Study: A Longitudinal Randomized Controlled Trial Protocol for a Multi-Modal Lifestyle Intervention Study to Reduce Dementia Risk in Healthy Older Adults.

Dementia is understood to arise from a mixed etiology, enveloping chronic inflammatory and vascular impacts on the brain, driven by a constellation of modifiable risk factors which are largely mediated by lifestyle-related behaviors. These risk factors manifest over a prolonged preclinical period and account for up to 40% of the population attributable risk for dementia, representing viable targets for early interventions aimed at abating disease onset and progression. Here we outline the protocol for a 12-week randomized control trial (RCT) of a multimodal Lifestyle Intervention Study for Dementia Risk Reduction (LEISURE), with longitudinal follow-up at 6-months and 24-months post-intervention. This trial integrates exercise, diet, sleep, and mindfulness to simultaneously target multiple different etiopathogenetic mechanisms and their interplay in a healthy older adult population (aged 50-85 years), and assesses dementia risk reduction as the primary endpoint. The LEISURE study is located in the Sunshine Coast region of Australia, which has one of the nation's highest proportions of adults aged over 50 years (36.4%), and corresponding dementia prevalence. This trial is novel in its inclusion of mindfulness and sleep as multidomain lifestyle targets, and in its comprehensive suite of secondary outcomes (based on psychological, physical health, sleep activity, and cognitive data) as well as exploratory neuroimaging (magnetic resonance imaging and electroencephalography) and molecular biology measures. These measures will provide greater insights into the brain-behavioral underpinnings of dementia prevention, as well as the predictors and impacts of the proposed lifestyle intervention. The LEISURE study was prospectively registered (ACTRN12620000054910) on 19 January 2020.

Immunomodulatory Function of Interleukin-15 and Its Role in Exercise, Immunotherapy, and Cancer Outcomes.

Exercise has been shown to improve physical and psychosocial outcomes for people across the cancer care continuum. A proposed mechanism underpinning the relationship between exercise and cancer outcomes is exercise-induced immunomodulation via secretion of anti-inflammatory myokines from skeletal muscle tissue. Myokines have the potential to impair cancer growth through modulation of natural killer (NK) cells and CD8+ T cells while improving the effectiveness of cancer therapies. Interleukin-15 (IL-15), one of the most abundant myokines found in skeletal muscle, has a key immunoregulatory role in supporting the proliferation and maturation of T cells and NK cells, which have a key role in the host's immune response to cancer. Furthermore, IL-15 is being explored clinically as an immunotherapy agent with doses similar to the IL-15 concentrations released by skeletal muscle during exercise. Here we review the role of IL-15 within the immune system, examine how IL-15 is produced as a myokine during exercise, and how it may improve outcomes for people with cancer, specifically as an adjuvant or neoadjuvant to immunotherapy. We summarize the available evidence showing changes in IL-15 in response to both acute exercise and training, and the results are inconsistent; higher quality research is needed to advance the understanding of how exercise-mediated increases in IL-15 potentially benefit those who are being treated for, or who have had, cancer.

Dietary Inflammatory Index and Associations with Sarcopenia Symptomology in Community-Dwelling Older Adults.

Low-grade systemic inflammation is a key driver of muscle degeneration in older adults, and diets with pro-inflammatory properties may further contribute to loss of muscle mass, strength and function. Therefore, this research aimed to explore the associations between the inflammatory potential of the diet and measures of sarcopenia symptomology in community-dwelling older adults. Upper (handgrip strength, HGS) and lower extremity (sit-to-stand) muscle strength, physical performance (timed-up-and-go, TUG) and appendicular skeletal muscle mass (ASM) was assessed according to the European Working Group on Sarcopenia in Older People version 2 (EWGSOP2) criteria. Multiple 24-hr dietary recalls were used to calculate the Dietary Inflammatory Index (DII), which was then used to group participants into anti- and pro-inflammatory dietary groups. Multiple linear regression investigated associations between DII, muscle strength, physical performance, and muscle quantity adjusted for age, gender, comorbidities, waist circumference and physical activity. Adults 65-85 years (n = 110, 72.1 ± 4.7 years, 76.4% female) were recruited. One participant was identified with sarcopenia, 35.2% were pre-frail, or frail. More participants with a pro-inflammatory DII score had low muscle quantity than those with anti-inflammatory DII (3.4% vs. 6.4%, x2 = 4.537, p = 0.043) and DII was negatively associated with HGS (ß = -0.157, p = 0.016) and ASM (ß = -0.176, p = 0.002) which remained significant after adjusting for covariates. In this population, DII was associated with less favorable muscle strength, physical performance, and muscle quantity.

Between-day reliability of cytokines and adipokines for application in research and practice.

Purpose: This study assessed the biological reliability of peripheral human cytokines and adipokines, and the influence of participant characteristics on total error. This has essential application to interventional cytokine measurement to ensure that reported results are interpreted with confidence. Methods: Participants (49% female, 18-85 years, n = 84) completed two consecutive-day testing sessions. Participants provided a venous blood sample at the same time of day across two consecutive days, under standardized participant presentation, including 24-h rested and 12-h fasted conditions. Multiplex immunoassay was used to assess inflammatory analytes from samples (predominantly plasma). Repeat measurements were conducted between-day for total precision quantification, and technical (technique) error was negated from the total to provide an estimate of biological (attributed to participant presentation) error. Results: Whilst there was no evidence of statistically significant biological error, a small amount of biological error was consistently present across most analytes (∼3.3%/0.07 pg/ml), which was largest for measurement of leptin (7.3%/210 pg/ml). There was also an influence of sex on reliability of leptin and adiponectin (total model explained 6-7% of error variation), where females demonstrated the greatest error. Conclusion: Biological error reported in this study should be applied to any future study or individual with a repeated measurement of cytokine concentrations over time that maintain best practice procedures (12-h fasted, 24-h rested). In most cases, raw error should be used, with exceptions for women for measurement of leptin and adiponectin. This approach will ensure that results are reported with certainty for improved reporting of intervention efficacy.

Sitting less and moving more for improved metabolic and brain health in type 2 diabetes: 'OPTIMISE your health' trial protocol.

BACKGROUND: Clinical practice guidelines recommend that adults with type 2 diabetes (T2D) sit less and move more throughout the day. The 18-month OPTIMISE Your Health Clinical Trial was developed to support desk-based workers with T2D achieve these recommendations. The two-arm protocol consists of an intervention and control arms. The intervention arm receives 6 months health coaching, a sit-stand desktop workstation and an activity tracker, followed by 6 months of text message support, then 6 months maintenance. The control arm receives a delayed modified intervention after 12 months of usual care. This paper describes the methods of a randomised controlled trial (RCT) evaluating the effectiveness and cost-effectiveness of the intervention, compared to a delayed intervention control. METHODS: This is a two-arm RCT being conducted in Melbourne, Australia. Desk-based workers (≥0.8 full-time equivalent) aged 35-65 years, ambulatory, and with T2D and managed glycaemic control (6.5-10.0% HbA1c), are randomised to the multicomponent intervention (target n = 125) or delayed-intervention control (target n = 125) conditions. All intervention participants receive 6 months of tailored health coaching assisting them to "sit less" and "move more" at work and throughout the day, supported by a sit-stand desktop workstation and an activity tracker (Fitbit). Participants receive text message-based extended care for a further 6-months (6-12 months) followed by 6-months of non-contact (12-18 months: maintenance). Delayed intervention occurs at 12-18 months for the control arm. Assessments are undertaken at baseline, 3, 6, 12, 15 and 18-months. Primary outcomes are activPAL-measured sitting time (h/16 h day), glycosylated haemoglobin (HbA1c; %, mmol/mol) and, cognitive function measures (visual learning and new memory; Paired Associates Learning Total Errors [adjusted]). Secondary, exploratory, and process outcomes will also be collected throughout the trial. DISCUSSION: The OPTIMISE Your Health trial will provide unique insights into the benefits of an intervention aimed at sitting less and moving more in desk-bound office workers with T2D, with outcomes relevant to glycaemic control, and to cardiometabolic and brain health. Findings will contribute new insights to add to the evidence base on initiating and maintaining behaviour change with clinical populations and inform practice in diabetes management. TRIAL REGISTRATION: ANZCTRN12618001159246 .

Characteristics of community-based exercise programs for community-dwelling older adults in rural/regional areas: a scoping review.

Community-based exercise programs for older adults play a potentially important role in mitigating the decline in functional outcomes, body composition, psychosocial outcomes, and cardiovascular health outcomes that commonly occurs with advancing age. There is a limited understanding of the characteristics and effectiveness of community-based exercise programs, particularly when those programs are offered outside metropolitan areas. Rural/regional settings face unique challenges, such as limited access to equipment/resources, transportation, and services, as well as significant costs to run programs. The objective of this scoping review was to characterise studies in the field that have aimed to implement community-based programs in settings identified as rural / regional. A secondary aim was to establish guidance for future exercise programs in this setting and highlight future research directions. A total of 12 studies were conducted in settings identified as rural/regional areas in various countries across the world were included. Of the included studies, five were randomised controlled trials. The majority of included studies reported on functional outcomes (83%) and psychosocial outcomes (75%), yet only 42% reported body composition, 17% reported cardiovascular health and 17% reported dietary outcomes. Low male representation was observed, with women outnumbering men in 7 of 12 studies. There was also minimal investigation of qualitative outcomes in existing community-based exercise programs in rural/regional settings, presenting a key gap for future research to address. Study Protocol: https://osf.io/txpm3/ . Date of registration: 20 July 2020.

Physical Activity, Mental Health and Wellbeing of Adults within and during the Easing of COVID-19 Restrictions, in the United Kingdom and New Zealand.

Physical activity (PA) participation was substantially reduced at the start of the COVID-19 pandemic. The purpose of this study was to assess the association between PA, mental health, and wellbeing during and following the easing of COVID-19 restrictions in the United Kingdom (UK) and New Zealand (NZ). In this study, 3363 adults completed online surveys within 2-6 weeks of initial COVID-19 restrictions (April/May 2020) and once restrictions to human movement had been eased. Outcome measures included the International Physical Activity Questionnaire Short-Form, Depression Anxiety and Stress Scale-9 (mental health) and World Health Organisation-5 Wellbeing Index. There were no differences in PA, mental health or wellbeing between timepoints (p > 0.05). Individuals engaging in moderate or high volume of PA had significantly better mental health (-1.1 and -1.7 units, respectively) and wellbeing (11.4 and 18.6 units, respectively) than individuals who engaged in low PA (p < 0.001). Mental health was better once COVID-19 restrictions were eased (p < 0.001). NZ had better mental health and wellbeing than the UK (p < 0.001). Participation in moderate-to-high volumes of PA was associated with better mental health and wellbeing, both during and following periods of COVID-19 containment, compared to participation in low volumes of PA. Where applicable, during the current or future pandemic(s), moderate-to-high volumes of PA should be encouraged.

Accuracy of body composition measurement techniques across the age span.

This study investigated the acceptable accuracy of common body composition techniques compared with the reference 4-compartment (4C-R) model, which has not been investigated in a sample with diverse characteristics, including age and sex. Techniques included components of the 4C-R model [dual-energy X-ray absorptiometry, air displacement plethysmography, deuterium dilution (DD)] and surrogate compartment models, which utilised bioelectrical impedance spectroscopy (BIS) rather than DD. Men and women (sex = 1:1, 18-85 years, n = 90) completed body composition testing under best-practice guidance. For measurement of individuals, only the reference 3-compartment (3C-R) equation met acceptable error limits (<5% error among individuals) within the a priori cut-point (80%) for fat-free mass (FFM; CV = 0.52%) and fat mass (FM; CV = 1.61%). However, all investigated techniques reached equivalency to the 4C-R model for FFM on average (CV = 0.52-4.31%), but for FM only the 3C and 4C equations that included quantification of total body water (TBW) by DD or BIS reached equivalency overall (CV = 1.61-6.68%). Sex and age minimally influenced accuracy. Only the 3C-R or 4C-R equations are supported for acceptable individual accuracy for both FFM and FM. For group estimates any investigated technique could be used with acceptable accuracy for FFM; however, for FM, inclusion of TBW measurement within a compartment model is necessary. Novelty: Only the referent 3C and 4C models (including deuterium dilution) provide accurate body composition results that are acceptable for measurement of individuals in the general population. For group estimates of lean mass in the general population, compartments models that include TBW must be used for accurate measurement.

The acute effects of aerobic exercise on sensorimotor adaptation in chronic stroke.

BACKGROUND: Sensorimotor adaptation, or the capacity to adapt movement to changes in the moving body or environment, is a form of motor learning that is important for functional independence (e.g., regaining stability after slips or trips). Aerobic exercise can acutely improve many forms of motor learning in healthy adults. It is not known, however, whether acute aerobic exercise has similar positive effects on sensorimotor adaptation in stroke survivors as it does in healthy individuals. OBJECTIVE: The aim of this study was to determine whether acute aerobic exercise promotes sensorimotor adaptation in people post stroke. METHODS: A single-blinded crossover study. Participants attended two separate sessions, completing an aerobic exercise intervention in one session and a resting control condition in the other session. Sensorimotor adaptation was assessed before and after each session, as was brain derived neurotrophic factor. Twenty participants with chronic stroke completed treadmill exercise at moderate to high intensity for 30 minutes. RESULTS: Acute aerobic exercise in chronic stroke survivors significantly increased sensorimotor adaptation from pre to post treadmill intervention. The 30-minute treadmill intervention resulted in an averaged 2.99 ng/ml increase in BDNF levels (BDNF pre-treadmill = 22.31 + /-2.85 ng/ml, post-treadmill was = 25.31 + /-2.46 pg/ml; t(16) = 2.146, p = 0.048, cohen's d = 0.521, moderate effect size). CONCLUSIONS: These results indicate a potential role for aerobic exercise to promote the recovery of sensorimotor function in chronic stroke survivors.

How body composition techniques measure up for reliability across the age-span.

BACKGROUND: Reliability of body composition measurement techniques is essential to the accurate reporting of intervention outcomes. However, the between-day precision error of commonly used techniques, as well as the reference multi-compartment model, in a population-representative sample are currently unknown. OBJECTIVES: To quantify technical and biological precision error of body composition techniques in comparison to the referent 4-compartment (4C) model. METHODS: Men and women (1:1 ratio; 18-85 years old; n = 90) completed 2 consecutive-day body composition testing sessions, including individual components of the referent 4C model. Testing was undertaken in accordance with best practice guidance for each technique, including standardized presentation and a consistent time of day. Repeat measurements were conducted on day 1 for technical precision, and between-day measurements were conducted for biological precision quantification. RESULTS: On average, all measurements met acceptable error limits and presented typically low technical and biological error [<2% fat-free mass (FFM) and < 3% fat mass (FM) precision error]. For technical precision of FFM, all techniques met a priori cut points (80%; CV = 0.45-0.81%). For FM, all techniques were equivalent to the best-rating method on average (CV = 0.78-1.35%), except air displacement plethysmography (CV = 2.13%). For biological precision, only 3-compartment (3C) and 4C equations sufficiently met the a priori determined cut point for estimates for FFM (CV = 0.77-0.79%), and only DXA met the 80% cut point (CV = 1.17%) for FM. CONCLUSIONS: The primary purpose of a study design is imperative when deciding on body composition assessment techniques used for longitudinal measurements. If reliable longitudinal assessments of FFM are central, a 3C or 4C model may be indicated. If FM is a primary outcome, DXA may be preferable. However, considering the low error rates presented within the current study across a broad age span of healthy adults with implementation of best-practice guidelines, any technique assessed here may be used, provided that strict protocols are adhered to.

The effect of exercise intensity on chronic inflammation: A systematic review and meta-analysis.

OBJECTIVES: Chronic inflammation is independently associated with the incidence and progression of chronic disease. Exercise has been found to reduce chronic inflammation, however the role of exercise intensity (work rate) is unknown. This review aimed to determine the pooled effect of higher- compared to lower-intensity aerobic and resistance exercise on chronic inflammation in adults. DESIGN: Systematic review and meta-analysis. METHODS: Five electronic databases were searched. Intervention trials that assessed the effect of ≥2 different exercise intensities on peripheral markers of chronic inflammation [c-reactive protein (CRP), interleukin (IL)-6, tumour necrosis factor (TNF)-α and IL-10] in adults were included. Random-effect meta-analyses were conducted to calculate the mean difference in change scores between groups [effect size (ES)]. Sub-group analyses were performed to explore the influence of age, chronic disease, body mass index and intervention duration on inflammation heterogeneity. RESULTS: Of 3952 studies identified, 27 were included. There were no significant effects of exercise intensity on IL-6 (ES=-0.039, 95%CI=-0.353-0.275; p=0.806), TNF-α (ES=0.296, 95%CI=-0.184-0.777; p=0.227) and IL-10 (ES=0.007, 95%CI=-0.904-0.919; p=0.987). A significant pooled ES was observed for higher- versus lower-intensity exercise on CRP concentrations, in studies of middle-aged adults (ES=-0.412, 95%CI=-0.821- -0.004, p=0.048) or interventions >9 weeks in duration (ES=-0.520, 95%CI=-0.882--0.159, p=0.005). CONCLUSIONS: Exercise intensity did not influence chronic inflammatory response. However, sub-analyses suggest that higher-intensity training may be more efficacious than lower-intensity for middle-aged adults, or when longer duration interventions are implemented (>9 weeks), in the most commonly-reported analyte (CRP).

Women Experience the Same Ergogenic Response to Caffeine as Men.

PURPOSE: This study aimed to determine whether 1) consumption of caffeine improves endurance cycling performance in women and 2) sex differences exist in the magnitude of the ergogenic and plasma responses to caffeine supplementation. METHODS: Twenty-seven (11 women and 16 men) endurance-trained cyclists and triathletes participated in this randomized, double-blind, placebo-controlled, crossover study. Participants completed an incremental exercise test to exhaustion, two familiarization trials, and two performance trials. Ninety minutes before the performance trials, participants ingested opaque capsules containing either 3 mg·kg body mass of anhydrous caffeine or a placebo. They then completed a set amount of work (75% of peak sustainable power output) in the fastest possible time. Plasma was sampled at baseline, preexercise, and postexercise for caffeine. Strict standardization and verification of diet, hydration, training volume and intensity, and contraceptive hormone phase (for women) were implemented. RESULTS: Performance time was significantly improved after caffeine administration in women (placebo: 3863 ± 419 s, caffeine: 3757 ± 312 s; P = 0.03) and men (placebo: 3903 ± 341 s, caffeine: 3734 ± 287 s; P < 0.001). The magnitude of performance improvement was similar for women (mean = 4.3%, 95% CI = 0.4%-8.2%) and men (4.6%, 2.3%-6.8%). Plasma caffeine concentrations were similar between sexes before exercise, but significantly greater in women after exercise (P < 0.001). CONCLUSIONS: Ingestion of 3 mg·kg body mass of caffeine enhanced endurance exercise performance in women. The magnitude of the performance enhancement observed in women was similar to that of men, despite significantly greater plasma caffeine concentrations after exercise in women. These results suggest that the current recommendations for caffeine intake (i.e., 3-6 mg·kg caffeine before exercise to enhance endurance performance), which are derived almost exclusively from studies on men, may also be applicable to women.

Use of Oral Contraceptives to Manipulate Menstruation in Young, Physically Active Women.

PURPOSE: Menstruation and menstrual symptoms are commonly cited barriers to physical activity in women. The delay or avoidance of menstruation through extended oral-contraceptive (OC) regimens may mitigate these barriers, yet information on menstrual-manipulation practices in young physically active women is sparse. The objective of this study was to investigate prevalence of, and reasons for, menstrual manipulation with OCs in recreationally and competitively active women. METHODS: One hundred ninety-one recreationally active (self-reported moderate to vigorous physical activity 150-300 min/wk) women (age 23 ± 5 y), 160 subelite recreationally active (self-reported moderate to vigorous physical activity >300 min/wk) women (age 23 ± 5 y), and 108 competitive (state-, national- or international-level) female athletes (age 23 ± 4 y) completed a self-administered questionnaire assessing OC-regimen habits and reasons for manipulation of menstruation. RESULTS: The majority (74%) of OC users reported having deliberately manipulated menstruation at least once during the previous year, with 29% reporting having done so at least 4 times. Prevalence of menstrual manipulation (at least once in the previous year) was not different between competitive athletes, subelite recreationally active women, and recreationally active women (77% vs 74% vs 72%; P > .05). The most cited reasons for manipulating menstruation were special events or holidays (rated by 75% as important/very important), convenience (54%), and sport competition (54%). CONCLUSIONS: Menstrual manipulation through extended OC regimens is common practice in recreationally and competitively active young women, for a range of reasons relating to convenience that are not limited to physical activity. This strategy may help reduce hormone-related barriers to exercise participation, thereby positively affecting participation and performance.

Three-step method for menstrual and oral contraceptive cycle verification.

OBJECTIVES: Fluctuating endogenous and exogenous ovarian hormones may influence exercise parameters; yet control and verification of ovarian hormone status is rarely reported and limits current exercise science and sports medicine research. The purpose of this study was to determine the effectiveness of an individualised three-step method in identifying the mid-luteal or high hormone phase in endogenous and exogenous hormone cycles in recreationally-active women and determine hormone and demographic characteristics associated with unsuccessful classification. DESIGN: Cross-sectional study design. METHODS: Fifty-four recreationally-active women who were either long-term oral contraceptive users (n=28) or experiencing regular natural menstrual cycles (n=26) completed step-wise menstrual mapping, urinary ovulation prediction testing and venous blood sampling for serum/plasma hormone analysis on two days, 6-12days after positive ovulation prediction to verify ovarian hormone concentrations. RESULTS: Mid-luteal phase was successfully verified in 100% of oral contraceptive users, and 70% of naturally-menstruating women. Thirty percent of participants were classified as luteal phase deficient; when excluded, the success of the method was 89%. Lower age, body fat and longer menstrual cycles were significantly associated with luteal phase deficiency. CONCLUSIONS: A step-wise method including menstrual cycle mapping, urinary ovulation prediction and serum/plasma hormone measurement was effective at verifying ovarian hormone status. Additional consideration of age, body fat and cycle length enhanced identification of luteal phase deficiency in physically-active women. These findings enable the development of stricter exclusion criteria for female participants in research studies and minimise the influence of ovarian hormone variations within sports and exercise science and medicine research.

Oral Contraceptive Use Dampens Physiological Adaptations to Sprint Interval Training.

PURPOSE: Oral contraceptive (OC) use reduces peak aerobic capacity (V˙O2peak); however, whether it also influences adaptations to training has yet to be determined. This study aimed to examine the influence of OC use on peak performance (peak power output [PPO]) and physiological adaptations (V˙O2peak and peak cardiac output [Q˙peak]) after sprint interval training (SIT) in recreationally active women. METHODS: Women taking an OC (n = 25) or experiencing natural regular menstrual cycles (MC; n = 16) completed an incremental exercise test to assess V˙O2peak, PPO, and Q˙peak before, immediately after, and 4 wk after 12 sessions of SIT. The SIT consisted ten 1-min efforts at 100% to 120% PPO in a 1:2 work-rest ratio. RESULTS: Though V˙O2peak increased in both groups after SIT (both P < 0.001), the MC group showed greater improvement (OC, +8.5%; MC, +13.0%; P = 0.010). Similarly, Q˙peak increased in both groups, with greater improvement in the MC group (OC, +4.0%; MC, +16.1%; P = 0.013). PPO increased in both groups (OC, +13.1%; MC, +13.8%; NS). All parameters decreased 4 wk after SIT cessation, but remained elevated from pretraining levels; the OC group showed more sustained training effects in V˙O2peak (OC, -4.0%; MC, -7.7%; P = 0.010). CONCLUSION: SIT improved peak exercise responses in recreationally active women. However, OC use dampened V˙O2peak and Q˙peak adaptation. A follow-up period indicated that OC users had spared V˙O2peak adaptations, suggesting that OC use may influence the time course of physiological training adaptations. Therefore, OC use should be verified, controlled for, and considered when interpreting physiological adaptations to exercise training in women.