Caring for Informal Dementia Caregivers and Their Loved Ones Via the HOMeCARE Exercise and Mindfulness for Health Program (HOMeCARE): A Randomized, Single-Blind, Controlled Trial.

Objective: To investigate the effects of a dyadic intervention of mindfulness-based stress reduction (MBSR) for informal dementia caregivers and home-based balance and progressive resistance training (PRT) for their loved ones. Methods: The study was a two arm, randomized, controlled, single-blinded, parallel-group trial. Dyads were randomized to an intervention group: an 8-week MBSR course (daily) and an 8-week PRT and balance training (3 days/week) for their loved ones or a waiting list control group. Results: Nine dyads were randomized [caregivers: median age 75 (40-81) years, loved ones: 77 (73-88) years]. The intervention significantly improved caregiver mindfulness [relative effect size (95% confidence interval) 1.35 (-0.10, 2.81); p = .009] and functional mobility in their loved ones [mean difference (95% confidence interval) 1.53 (-3.09, 6.14)] with no significant effects on caregiver burden [relative effect size (95% confidence interval) 0.22 (-1.09, 1.54); p = .622]. Conclusion: The study appeared feasible in the home environment and future large and longer trials should test the efficacy of a more abbreviated MBSR intervention and to optimize adoption and sustain adherence over time. Trial registry name: HOMeCare: Caring for the Dementia Caregiver and their Loved One via the HOMeCare Exercise and Mindfulness for Health Program Trial URL: https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12617000347369 Registration number: ACTRN12617000347369.

National survey of Australian cardiac rehabilitation programmes: does current exercise programming adhere to evidence-based guidelines and best practice?

Objectives: The efficacy of exercise-based cardiac rehabilitation (CR) for patient outcomes is well established, with better outcomes when delivery meets recommended guidelines. The aim of this study was to assess how well Australian practice aligns with national CR guidelines for exercise assessment and prescription. Method: This cross-sectional online survey was distributed to all 475 publicly listed CR services in Australia and consisted of four sections: (1) Programme and client demographics, (2) aerobic exercise characteristics, (3) resistance exercise characteristics and (4) pre-exercise assessment, exercise testing and progression. Results: In total, 228 (54%) survey responses were received. Only three of five Australian guideline recommendations were consistently reported to be followed in current CR programmes: assessment of physical function prior to exercise (91%), prescription of light-moderate exercise intensity (76%) and review of referring physician results (75%). Remaining guidelines were commonly not implemented. For example, only 58% of services reported an initial assessment of resting ECG/heart rate, and only 58% reported the concurrent prescription of both aerobic and resistance exercise, which may have been influenced by equipment availability (p<0.05). Exercise-specific assessments such as muscular strength (18%) and aerobic fitness (13%) were uncommonly reported, although both were more frequent in metropolitan services (p<0.05) or when an exercise physiologist was present (p<0.05). Conclusions: Clinically relevant deficits in national CR guideline implementation are common, potentially influenced by location, exercise supervisor and equipment availability. Key deficiencies include the lack of concurrent aerobic and resistance exercise prescription and infrequent assessment of important physiological outcomes including resting heart rate, muscular strength and aerobic fitness.

Promoting independence in Lewy body dementia through exercise: the PRIDE study.

BACKGROUND: Lewy body dementia (LBD) is an aggressive type of dementia of rapid, fluctuating disease trajectory, higher incidence of adverse events, and poorer functional independence than observed in Alzheimer's disease dementia. Non-pharmacological treatments such as progressive, high-intensity exercise are effective in other neurological cohorts but have been scarcely evaluated in LBD. METHODS: The Promoting Independence in Lewy Body Dementia through Exercise (PRIDE) trial was a non-randomised, non-blinded, crossover pilot trial involving older adults with LBD consisting of a baseline assessment, an 8-week wait-list, and an 8-week exercise intervention. The aims of this study were to evaluate the determinants of the primary outcome functional independence, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale, and the feasibility and preliminary efficacy of an exercise intervention on this outcome. Additionally, important clinical characteristics were evaluated to explore associations and treatment targets. The exercise intervention was supervised, clinic-based, high-intensity progressive resistance training (PRT), challenging balance, and functional exercises, 3 days/week. RESULTS: Nine participants completed the baseline cross-sectional study, of which five had a diagnosis of Parkinson's disease dementia (PDD), and four dementia with Lewy Bodies (DLB). Six completed the exercise intervention (three PDD, three DLB). The cohort was diverse, ranging from mild to severe dementia and living in various residential settings. Greater functional independence at baseline was significantly associated with better physical function, balance, cognition, quality of life, muscle mass ratio, walking endurance, faster walking speed and cadence, and lower dementia severity (p < 0.05). Participants declined by clinically meaningful amounts in functional independence, cognition, physical function, muscle mass, and weight over the wait-list period (p < 0.05). Following exercise, participants improved by clinically meaningful amounts in functional independence, cognition, physical function, and strength (p < 0.05). Progressive, high intensity exercise was well-tolerated (> 80% adherence), and only one minor exercise-related adverse event occurred. CONCLUSIONS: PRIDE is the first exercise trial conducted specifically within individuals diagnosed with LBD, and provides important insight for the design of larger, randomized trials for further evaluation of progressive, high-intensity exercise as a valuable treatment in LBD. TRIAL REGISTRATION: The PRIDE trial protocol has previously been prospectively registered (08/04/2016, ANZCTR: ACTRN12616000466448).

Effect of aerobic exercise on waist circumference in adults with overweight or obesity: A systematic review and meta-analysis.

Excess visceral adiposity contributes to elevated cardiometabolic risk, and waist circumference is commonly used as a surrogate measure of visceral adipose tissue. Although regular aerobic exercise is known to improve abdominal obesity, its effect on waist circumference is unclear. A systematic review and meta-analysis was performed to determine (1) the effect of aerobic exercise on waist circumference in adults with overweight or obesity; (2) the association between any change in waist circumference and change in visceral adipose tissue and/or bodyweight with aerobic exercise interventions; and (3) if reductions in waist circumference with exercise are moderated by clinical characteristics or components of aerobic exercise prescription. Twenty-five randomized controlled trials (1686 participants) were included. Regular aerobic exercise significantly reduced waist circumference by 3.2 cm (95% confidence interval [CI] -3.86, -2.51, p ≤ 0.001) versus control. Change in waist circumference was associated with change in visceral adipose tissue (ß = 4.02; 95% CI 1.37, 6.66, p = 0.004), and vigorous intensity produced superior reduction (-4.2 cm, 95% CI -4.99, -3.42, p < 0.0001) in waist circumference compared with moderate intensity (-2.50 cm, 95% CI -3.22, -1.79, p = 0.058). These findings suggest regular aerobic exercise results in modest reductions in waist circumference and associated visceral adipose tissue and that higher intensity exercise may offer superior benefit to moderate intensity.

Effect of High-Intensity Power Training on Cognitive Function in Older Adults With Type 2 Diabetes: Secondary Outcomes of the GREAT2DO Study.

We sought to determine the effects of 12 months of power training on cognition, and whether improvements in body composition, muscle strength, and/or aerobic capacity (VO2peak) were associated with improvements in cognition in older adults with type 2 diabetes (T2D). Participants with T2D were randomized to power training or low-intensity sham exercise control condition, 3 days per week for 12 months. Cognitive outcomes included memory, attention/speed, executive function, and global cognition. Other relevant outcomes included VO2peak, strength, and whole body and regional body composition. One hundred and three adults with T2D (mean age 67.9 years; standard deviation [SD] 5.9; 50.5% women) were enrolled and analyzed. Unexpectedly, there was a nearly significant improvement in global cognition (p = .05) in the sham group relative to power training, although both groups improved over time (p < .01). There were significant interactions between group allocation and body composition or muscle strength in the models predicting cognitive changes. Therefore, after stratifying by group allocation, improvements in immediate memory were associated with increases in relative skeletal muscle mass (r = 0.38, p = .03), reductions in relative body fat (r = -0.40, p = .02), and increases in knee extension strength were directly related to changes in executive function (r = -0.41, p = .02) within the power training group. None of these relationships were present in the sham group (p > .05). Although power training did not significantly improve cognition compared to low-intensity exercise control, improvements in cognitive function in older adults were associated with hypothesized improvements in body composition and strength after power training.

The Effectiveness of Exercise as an Adjunct Intervention to Improve Quality of Life and Mood in Substance Use Disorder: A Systematic Review.

Introduction: Quality of life and affective outcomes offer a perspective of the burden of disease experienced by people with substance use disorder. This can be considered an alternative measure of substance use disorder severity. This review aims to evaluate the impact of exercise as a novel intervention on quality of life and affect in substance use disorder. Method: Medline, CINAHL, Amed, Web of Science core collections, Embase, PsychINFO and SportDISCUS databases were searched from inception to August 2021 for studies that assessed the impact of exercise on mood, depression, anxiety and quality of life outcomes in substance use disorder. Exercise interventions of any duration were included. Results: Forty-two studies met the inclusion criteria. Quality of life scores improved with larger effects seen in studies with two or more sessions per week. Depression and anxiety scores decreased, with 19 of the 25 data sets reporting a reduction in depression (effect size 0.2-1.86) and 13 of the 17 data sets reporting a reduction in anxiety (effect sizes 0.2-1.42). Mood improved in six of the seven data sets reviewed with effect sizes ranging from 0.34 to 1.13. Discussion: Included studies had numerous methodological flaws therefore results need to be interpreted with caution. Further research needs to be completed with more rigorous methodologies to support these results. Conclusions: Results indicate promising responses to exercise as a novel intervention for quality of life and mood in substance use disorder, however further research of high methodological quality is needed to confirm.

Study protocol for the BRAIN Training Trial: a randomised controlled trial of Balance, Resistance, And INterval training on cognitive function in older adults with mild cognitive impairment.

INTRODUCTION: Epidemiological evidence suggests that both poor cardiovascular fitness and low muscle mass or strength markedly increase the rate of cognitive decline and incident dementia in older adults. Results from exercise trials for the improvement of cognition in older adults with mild cognitive impairment (MCI) have reported mixed results. This is possibly due to insufficient exercise intensities. The aim of the Balance, Resistance, And INterval (BRAIN) Training Trial is to determine the effects of two forms of exercise, high-intensity aerobic interval training (HIIT) and high-intensity power training (POWER) each compared with a sham exercise control group on cognition in older adults with MCI. METHODS AND ANALYSIS: One hundred and sixty community-dwelling older (≥ 60 years) people with MCI have been randomised into the trial. Interventions are delivered supervised 2-3 days per week for 12 months. The primary outcome measured at baseline, 6 and 12 months is performance on a cognitive composite score measuring the executive domain calculated from a combination of computerised (NeuroTrax) and paper-and-pencil tests. Analyses will be performed via repeated measures linear mixed models and generalised linear mixed models of baseline, 6-month and 12-month time points, adjusted for baseline values and covariates selected a priori. Mixed models will be constructed to determine the interaction of GROUP × TIME. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Sydney (HREC Ref.2017/368), University of Queensland (HREC Ref. 2017/HE000853), University of British Columbia (H16-03309), and Vancouver Coastal Health Research Institute (V16-03309) Human Research Ethics. Dissemination will be via publications, conference presentations, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers.It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT and POWER on subclinical markers of disease. TRIAL REGISTRATION NUMBER: ACTRN12617001440314 Australian New Zealand Clinical Trials Registry.

Nutrition Module design in Maintain Your Brain: an internet-based randomised controlled trial to prevent cognitive decline and dementia.

The Maintain Your Brain (MYB) trial is one of the largest internet-delivered multidomain randomised controlled trial designed to target modifiable risk factors for dementia. It comprises four intervention modules: physical activity, nutrition, mental health and cognitive training. This paper explains the MYB Nutrition Module, which is a fully online intervention promoting the adoption of the 'traditional' Mediterranean Diet (MedDiet) pattern for those participants reporting dietary intake that does not indicate adherence to a Mediterranean-type cuisine or those who have chronic diseases/risk factors for dementia known to benefit from this type of diet. Participants who were eligible for the Nutrition Module were assigned to one of the three diet streams: Main, Malnutrition and Alcohol group, according to their medical history and adherence to the MedDiet at baseline. A short dietary questionnaire was administered weekly during the first 10 weeks and then monthly during the 3-year follow-up to monitor whether participants adopted or maintained the MedDiet pattern during the intervention. As the Nutrition Module is a fully online intervention, resources that promoted self-efficacy, self-management and process of change were important elements to be included in the module development. The Nutrition Module is unique in that it is able to individualise the dietary advice according to both the medical and dietary history of each participant; the results from this unique intervention will contribute substantively to the evidence that links the Mediterranean-type diet with cognitive function and the prevention of dementia and will increase our understanding of the benefits of a MedDiet in a Western country.

Caffeine alters thermoregulatory responses to exercise in the heat only in caffeine-habituated individuals: a double-blind placebo-controlled trial.

To assess the impact of acute caffeine ingestion on thermoregulatory responses during steady-state exercise under moderate heat stress conditions in caffeine-habituated and nonhabituated individuals. Twenty-eight participants [14 habituated (HAB) (4 females) and 14 nonhabituated (NHAB) (6 females)] cycled at a fixed metabolic heat production (7 W·kg-1) for 60 min on two separate occasions 1 h after ingesting 1) 5 mg·kg-1 caffeine (CAF) or 2) 5 mg·kg-1 placebo (PLA), in a double-blinded, randomized, and counterbalanced order. Environmental conditions were 30.6 ± 0.9°C, 31 ± 1% relative humidity (RH). The end-exercise rise in esophageal temperature (ΔTes) from baseline was greater with CAF in the HAB group (CAF = 0.88 ± 0.29°C, PLA = 0.62 ± 0.34°C, P < 0.001), but not in the NHAB group (CAF = 1.00 ± 0.42°C, PLA = 1.00 ± 0.39°C, P = 0.94). For a given change in mean body temperature, rises in % of maximum skin blood flow were attenuated with CAF on the forearm (P = 0.015) and back (P = 0.021) in the HAB group, but not in the NHAB group (P ≥ 0.65). Dry heat loss was similar in the HAB (CAF = 31 ± 5 W·m-2, PLA = 33 ± 7 W·m-2) and NHAB groups (CAF = 31 ± 3 W·m-2, PLA 30 ± 4 W·m-2) (P ≥ 0.37). There were no differences in whole body sweat losses in both groups (HAB: CAF = 0.59 ± 0.15 kg, PLA = 0.56 ± 0.17 kg, NHAB:CAF = 0.53 ± 0.19 kg, PLA 0.52 ± 0.19 kg) (P ≥ 0.32). As the potential for both dry and evaporative heat loss was uninhibited by caffeine, we suggest that the observed ΔTes differences with CAF in the HAB group were due to alterations in internal heat distribution. Our findings support the common practice of participants abstaining from caffeine before participation in thermoregulatory research studies in compensable conditions.NEW & NOTEWORTHY We provide empirical evidence that acute caffeine ingestion exerts a thermoregulatory effect during exercise in the heat in caffeine-habituated individuals but not in nonhabituated individuals. Specifically, caffeine habituation was associated with a greater rise in esophageal temperature with caffeine compared with placebo, which appears to be driven by a blunted skin blood flow response. In contrast, no thermoregulatory differences were observed with caffeine in nonhabituated individuals. Caffeine did not affect sweating responses during exercise in the heat.

The Effect of High-Intensity Power Training on Habitual, Intervention and Total Physical Activity Levels in Older Adults with Type 2 Diabetes: Secondary Outcomes of the GREAT2DO Randomized Controlled Trial.

BACKGROUND: We examined the effect of power training on habitual, intervention and total physical activity (PA) levels in older adults with type 2 diabetes and their relationship to metabolic control. MATERIALS AND METHODS: 103 adults with type 2 diabetes were randomized to receive supervised power training or sham exercise three times/week for 12 months. Habitual, intervention, and total PA, as well as insulin resistance (HOMA2-IR) and glycosylated hemoglobin (HbA1c), were measured. RESULTS: Participants were aged 67.9 ± 5.5 yrs, with well-controlled diabetes (HbA1c = 7.1%) and higher than average habitual PA levels compared to healthy peers. Habitual PA did not change significantly over 12 months (p = 0.74), and there was no effect of group assignment on change over time in habitual PA over 0-6 (p = 0.16) or 0-6-12 months (p = 0.51). By contrast, intervention PA, leg press tonnage and total PA increased over both 6- and 12-month timepoints (p = 0.0001), and these changes were significantly greater in the power training compared to the sham exercise group across timepoints (p = 0.0001). However, there were no associations between changes in any PA measures over time and changes in metabolic profile. CONCLUSION: Structured high-intensity power training may be an effective strategy to enhance overall PA in this high-risk cohort.

Electronic food records among middle-aged and older people: A comparison of self-reported and dietitian-assisted information.

AIM: Nutrition-based applications ("apps") offer enormous research potential, however evidence of their use and acceptability among older adults is limited. We compared self-reported and dietitian-adjusted dietary intake records among adults aged 55 to 75 years using the Research Food Diary (RFD) app. METHODS: Participants were recruited from the 45 and Up Study and completed a 3-day food record using the RFD. A follow-up dietetic telephone interview was performed to confirm the electronic dietary data. Independent of these interviews, a set of adjustments based on dietetic skills, nutritional database knowledge, food composition and dietary assessment was established to resolve probable reporting errors. The "adjusted" and "dietitian-assisted" records were compared to self-reported records for nutrient intakes and serves of The Five Food Groups using one-way repeated measures analysis of variance. RESULTS: Sixty-two participants were recruited, with 48 using the RFD app which included eight records without any identified errors. Reporting errors contained in the raw self-reported records included: food items with missing/implausible quantities or insufficient descriptions to allow automatic coding. After removal of unusable records, 44 records were analysed. Differences were found between the self-reported and adjusted records for protein, calcium, vitamin B12 , zinc and dairy food serves (all P < .001; differences up to 8%). No significant differences were found between the adjusted and dietitian-assisted measures. CONCLUSIONS: Similarities between adjusted and dietitian-assisted records suggest carefully applied dietetic assumptions are likely to improve accuracy of self-reported intake data where dietitian interviews are not possible. We provide four key recommendations to guide this process.

Effect of Training Phase on Physical and Physiological Parameters of Male Powerlifters.

Longitudinal research on training and dietary practices of natural powerlifters is limited. This study investigated the effect of phases of training on physical and physiological parameters in male natural powerlifters. Nine participants completed testing at two time points: (i) preparatory phase (~3 months prior to a major competition) and (ii) competition phase (1-2 weeks from a major competition). No significant changes between training phases were found for muscle strength and power. A trend for significance was found for decreased muscle endurance of the lower body (-24.4%, p = 0.08). A significant increase in leg lean mass was found at the competition phase (2.3%, p = 0.04), although no changes for other body composition measures were observed. No change was observed for any health marker except a trend for increased urinary creatinine clearance at the competition phase (12.5%, p = 0.08). A significant reduction in training volume for the lower body (-75.0%, p = 0.04) and a trend for a decrease in total energy intake (-17.0%, p = 0.06) was observed during the competition phase. Despite modifications in training and dietary practices, it appears that muscle performance, body composition, and health status remain relatively stable between training phases in male natural powerlifters.

Genomewide Association Study of Acute Anterior Uveitis Identifies New Susceptibility Loci.

Purpose: Acute anterior uveitis (AAU) is a common intraocular inflammatory disease. AAU occurs in 30% to 50% of patients with ankylosing spondylitis (AS), and both conditions are strongly associated with human leukocyte antigen (HLA)-B27, implying a shared etiology. This study aims to apply genomewide association study (GWAS) to characterize the genetic associations of AAU and their relationship to the genetics of AS. Methods: We undertook the GWAS analyses in 2752 patients with AS with AAU (cases) and 3836 patients with AS without AAU (controls). There were 7,436,415 single-nucleotide polymorphisms (SNPs) available after SNP microarray genotyping, imputation, and quality-control filtering. Results: We identified one locus associated with AAU at genomewide significance: rs9378248 (P = 2.69 × 10-8, odds ratio [OR] = 0.78), lying close to HLA-B. Suggestive association was observed at 11 additional loci, including previously reported AS loci ERAP1 (rs27529, P = 2.19 × 10-7, OR = 1.22) and NOS2 (rs2274894, P = 8.22 × 10-7, OR = 0.83). Multiple novel suggestive associations were also identified, including MERTK (rs10171979, P = 2.56 × 10-6, OR = 1.20), KIFAP3 (rs508063, P = 5.64 × 10-7, OR = 1.20), CLCN7 (rs67412457, P = 1.33 × 10-6, OR = 1.25), ACAA2 (rs9947182, P = 9.70 × 10-7, OR = 1.37), and 5 intergenic loci. The SNP-based heritability is approximately 0.5 for AS alone, and is much higher (approximately 0.7) for AS with AAU. Consistent with the high heritability, a genomewide polygenic risk score shows strong power in identifying individuals at high risk of either AS with AAU or AS alone. Conclusions: We report here the first GWAS for AAU and identify new susceptibility loci. Our findings confirm the strong overlap in etiopathogenesis of AAU with AS, and also provide new insights into the genetic basis of AAU.

Interrupting the trajectory of frailty in dementia with Lewy bodies with anabolic exercise, dietary intervention and deprescribing of hazardous medications.

An 87-year-old man with dementia with Lewy bodies, living in residential aged care, exhibited rapid functional decline and weight loss associated with injurious falls over 9 months. Independent clinicians (geriatrician and exercise physiologist) assessed him during an extended wait-list period prior to his commencement of a pilot exercise trial. The highly significant role of treatable factors including polypharmacy, sarcopenia and malnutrition as contributors to frailty and rapid functional decline in this patient are described. The results of a targeted intervention of deprescribing, robust exercise and increased caloric intake on his physical and neuropsychological health status are presented. This case highlights the need to aggressively identify and robustly treat reversible contributors to frailty, irrespective of advanced age, progressive 'untreatable' neurodegenerative disease and rapidly deteriorating health in such individuals. Frailty is not a contraindication to robust exercise; it is, in fact, one of the most important reasons to prescribe it.

Relationship Between Disease Specific Quality of Life Measures, Physical Performance, and Activity in People with Intermittent Claudication Caused by Peripheral Artery Disease.

OBJECTIVE: The aims of this study were firstly to assess the correlation between disease specific measures of quality of life (QOL) and physical performance and activity, and secondly to identify demographic, clinical, functional, and physical activity measures independently associated with QOL in people with intermittent claudication. METHODS: This was a cross sectional observational study of 198 people with intermittent claudication caused by peripheral artery disease who were recruited prospectively. QOL was assessed with the intermittent claudication questionnaire (ICQ) and the eight-theme peripheral artery disease quality of life questionnaire. Physical performance was assessed with the six minute walk test (6MWT) and short physical performance battery (SPPB), and an accelerometer was used to measure seven day step count. The associations between QOL scores and 6MWT distance, SPPB scores and seven day step count were examined using Spearman Rho's (ρ) correlation and multivariable linear regression. RESULTS: ICQ scores were significantly correlated with 6MWT distance (ρ = 0.472, p < .001), all four SPPB scores (balance ρ = 0.207, p = .003; gait speed ρ = 0.303, p < .001; chair stand ρ = 0.167, p = .018; total ρ = 0.265, p < .001), and seven day step count (ρ = 0.254, p < .001). PADQOL social relationships and interactions (ρ = 0.343, p < .001) and symptoms and limitations in physical functioning (ρ = 0.355, p < .001) themes were correlated with 6MWT distance. The 6MWT distance was independently positively associated with ICQ and both PADQOL theme scores (ICQ: B 0.069, p < .001; PADQOL social relationships and interactions: B 0.077, p < .001; PADQOL symptoms and limitations in physical functioning: B 0.069, p < .001). CONCLUSION: Longer 6MWT distance independently predicted better physical and social aspects of QOL in people with intermittent claudication supporting its value as an outcome measure.

Fully-Online, Interoperable Clinical Trial Management System for Multi-Interventional RCT: Maintain Your Brain Digital Platform.

Maintain Your Brain (MYB)i is a randomised controlled trial (RCT) of multiple online interventions designed to target modifiable risk factors for Alzheimer's disease and dementia. Traditional clinical trial management systems (CTMS) requirements consist of features such as management of the study, site, subject (participant), clinical outcomes, external and internal requests, education, data extraction and reporting, security, and privacy. In addition to fulfilling these traditional requirements, MYB has a specific set of features that needs to be fulfilled. These specific requirements include: (i) support for multiple interventions within a study, (ii) flexible interoperability options with third-party software providers, (iii) study participants being able to engage in online activities via web-based interfaces throughout the trial (from screening to follow-up), (iv) ability to algorithmically personalize trial activities based on the needs of the participant, and (v) the ability to handle large volumes of data over a long period. This paper outlines how the existing CTMSs fall short in meeting these specific requirements. The presented system architecture, development approach and lessons learned in the implementation of the MYB digital platform will inform researchers attempting to implement CTMSs for trials comparable to MYB in the future.

Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI.

Dementia affects 47 million individuals worldwide, and assuming the status quo is projected to rise to 150 million by 2050. Prevention of age-related cognitive impairment in older persons with lifestyle interventions continues to garner evidence but whether this can combat underlying neurodegeneration is unknown. The Study of Mental Activity and Resistance Training (SMART) trial has previously reported within-training findings; the aim of this study was to investigate the long-term neurostructural and cognitive impact of resistance exercise in Mild Cognitive Impairment (MCI). For the first time we show that hippocampal subareas particularly susceptible to volume loss in Alzheimer's disease (AD) are protected by resistance exercise for up to one year after training. One hundred MCI participants were randomised to one of four training groups: (1) Combined high intensity progressive resistance and computerised cognitive training (PRT+CCT), (2) PRT+Sham CCT, (3) CCT+Sham PRT, (4) Sham physical+sham cognitive training (SHAM+SHAM). Physical, neuropsychological and MRI assessments were carried out at baseline, 6 months (directly after training) and 18 months from baseline (12 months after intervention cessation). Here we report neuro-structural and functional changes over the 18-month trial period and the association with global cognitive and executive function measures. PRT but not CCT or PRT+CCT led to global long-term cognitive improvements above SHAM intervention at 18-month follow-up. Furthermore, hippocampal subfields susceptible to atrophy in AD were protected by PRT revealing an elimination of long-term atrophy in the left subiculum, and attenuation of atrophy in left CA1 and dentate gyrus when compared to SHAM+SHAM (p = 0.023, p = 0.020 and p = 0.027). These neuroprotective effects mediated a significant portion of long-term cognitive benefits. By contrast, within-training posterior cingulate plasticity decayed after training cessation and was unrelated to long term cognitive benefits. Neither general physical activity levels nor fitness change over the 18-month period mediated hippocampal trajectory, demonstrating that enduring hippocampal subfield plasticity is not a simple reflection of post-training changes in fitness or physical activity participation. Notably, resting-state fMRI analysis revealed that both the hippocampus and posterior cingulate participate in a functional network that continued to be upregulated following intervention cessation. Multiple structural mechanisms may contribute to the long-term global cognitive benefit of resistance exercise, developing along different time courses but functionally linked. For the first time we show that 6 months of high intensity resistance exercise is capable of not only promoting better cognition in those with MCI, but also protecting AD-vulnerable hippocampal subfields from degeneration for at least 12 months post-intervention. These findings emphasise the therapeutic potential of resistance exercise; however, future work will need to establish just how long-lived these outcomes are and whether they are sufficient to delay dementia.

Resistance training as a treatment for older persons with peripheral artery disease: a systematic review and meta-analysis.

OBJECTIVE: Resistance training (RT) improves walking ability in persons with peripheral artery disease. We conducted a meta-analysis of randomised controlled trials (RCTs) investigating the effect of RT on peripheral artery disease (as measured by walking ability). DESIGN: We included RCTs that investigated the effect of RT on treadmill and/or 6 min walk (6-MWT) distances. RT intensity was assessed according to the American College of Sports Medicine guidelines by 1 repetition maximum or rating of perceived exertion. Standardised mean (SMD) and mean differences (MD) were calculated using a random-effects inverse variance model. Heterogeneity and bias were assessed using RevMan V.5.3. Meta-regression and meta-analysis of variance were performed as moderator analyses. DATA SOURCES: Databases (Medline, Embase, Web of Science, Cinahl and Google Scholar) were searched until July 2018. RESULTS: Fifteen trials isolated RT; 7 trials compared RT with aerobic exercise. We analysed 826 patients (n=363 completing RT), with a mean age of 67.1±3.8 years. Training ranged from low-high intensity, 2-7 times per week for 17±7 weeks, with a mix of upper, lower or whole body training. Overall RT significantly improved constant load treadmill claudication onset (COD) (SMD 0.66 [0.40, 0.93], p<0.00001) and total walking distance (WD) (SMD 0.51 [0.23, 0.79], p=0.0003), progressive treadmill COD (SMD 0.56 [0.00, 1.13], p=0.05) and total WD (SMD 0.45 [0.08, 0.83], p=0.02), and 6-MWT COD (MD 82.23 m [40.91, 123.54], p<0.0001). Intensity played a role in improvement, with high-intensity training yielding the greatest improvement (p=0.02). CONCLUSIONS: RT clinically improved treadmill and flat ground walking ability in persons with peripheral artery disease. Higher intensity training was associated with better outcomes. Our study makes a case for clinicians to include high-intensity lower body RT in the treatment of peripheral artery disease. TRIAL REGISTRATION NUMBER: CRD42017081184.