Reduced Body Flexibility Is Associated With Poor Survival in Middle-Aged Men and Women: A Prospective Cohort Study.

OBJECTIVES: Flexibility is recognized as one of the components of physical fitness and commonly included as part of exercise prescriptions for all ages. However, limited data exist regarding the relationship between flexibility and survival. We evaluated the sex-specific nature and magnitude of the associations between body flexibility and natural and non-COVID-19 mortality in a middle-aged cohort of men and women. DESIGN: Prospective cohort study. METHODS: Anthropometric, health and vital data from 3139 (66% men) individuals aged 46-65 years spanning from March 1994 to October 2022 were available. A body flexibility score, termed Flexindex, was derived from a combination of 20 movements (scored 0-4) involving seven different joints, resulting in a score range of 0-80. Kaplan-Meier survival curves were obtained, and unadjusted and adjusted hazard ratios (HRs) for mortality estimated. RESULTS: During a mean follow-up of 12.9 years, 302 individuals (9.6%) comprising 224 men/78 women died. Flexindex was 35% higher in women compared to men (mean ± SD: 41.1 ± 9.4 vs. 30.5 ± 8.7; p < 0.001) and exhibited an inverse relationship with mortality risk in both sexes (p < 0.001). Following adjustment for age, body mass index, and health status, the HR (95% CI) for mortality comparing upper and bottom of distributions of Flexindex were 1.87 (1.50-2.33; p < 0.001) for men and 4.78 (1.23-31.71; p = 0.047) for women. CONCLUSIONS: A component of physical fitness-body flexibility-as assessed by the Flexindex is strongly and inversely associated with natural and non-COVID-19 mortality risk in middle-aged men and women. Future studies should assess whether training-induced flexibility gains are related to longer survival.

Counseling Intervention and Cardiovascular Events in People With Peripheral Artery Disease: A Post Hoc Analysis of the BIP Randomized Clinical Trial.

Importance: It is unclear whether counseling to promote walking reduces the risk of major adverse cardiovascular events (MACE) in people with peripheral artery disease (PAD). Objective: To test whether a counseling intervention designed to increase walking reduced the risk of MACE in patients with PAD. Design, Setting, and Participants: The BIP trial was a randomized clinical trial, with recruitment performed between January 2015 and July 2018 and follow-up concluded in August 2023. Participants with walking impairment due to PAD from vascular departments in the Australian cities of Brisbane, Sydney, and Townsville were randomly allocated 1:1 to the intervention or control group. Data were originally analyzed in March 2024. Intervention: Four brief counseling sessions aimed to help patients with the challenges of increasing physical activity. Main Outcomes and Measures: The primary outcome was the between-group difference in risk of MACE, which included myocardial infarction (MI), stroke, and cardiovascular death. The relationship between Intermittent Claudication Questionnaire (ICQ) scores, PAD Quality of Life (PADQOL) scores, and MACE was examined with Cox proportional hazard regression analyses. Results: A total of 200 participants were included, with 102 allocated to the counseling intervention (51.0%) and 98 to the control group (49.0%).Participants were followed up for a mean (SD) duration of 3.5 (2.6) years. Median (IQR) participant age was 70 (63-76) years, and 56 of 200 participants (28.0%) were female. A total of 31 individuals had a MACE (composed of 19 MIs, 4 strokes, and 8 cardiovascular deaths). Participants allocated to the intervention were significantly less likely to have a MACE than participants in the control group (10 of 102 participants [9.8%] vs 21 of 98 [21.4%]; hazard ratio [HR], 0.43; 95% CI, 0.20-0.91; P = .03). Greater disease-specific quality of life (QOL) scores at 4 months (ICQ: HR per 1-percentage point increase, 0.97; 95% CI, 0.95-0.99; P < .001; PADQOL factor 3 [symptoms and limitations in physical functioning]: HR per 1-unit increase, 0.91; 95% CI, 0.84-0.98; P = .01) and at 12 months (ICQ: HR per 1-percentage point increase, 0.97; 95% CI, 0.95-0.99; P = .003; PADQOL factor 3: HR per 1-unit increase, 0.91; 95% CI, 0.84-0.98; P = .02) were associated with a lower risk of MACE. In analyses adjusted for ICQ or PADQOL factor 3 scores at either 4 or 12 months, allocation to the counseling intervention was no longer significantly associated with a lower risk of MACE. Conclusions and Relevance: This post hoc exploratory analysis of the BIP randomized clinical trial suggested that the brief counseling intervention designed to increase walking may reduce the risk of MACE, possibly due to improvement in QOL. Trial Registration: anzctr.org.au Identifier: ACTRN12614000592640.

Multifaceted Interventions Inclusive of Medication Optimization for Frailty in Aged Care: A Systematic Review.

OBJECTIVES: Implementation of best practice frailty guidelines in residential aged care is currently unclear, and there is a particular scarcity of evidence regarding multifaceted frailty treatments inclusive of medication optimization in these settings, despite the bidirectional relationship between polypharmacy and frailty. This review aimed to retrieve all relevant literature and evaluate the effect of medication optimization delivered in conjunction with exercise and/or nutritional interventions in the best-practice management of frailty in residential aged care. DESIGN: Systematic review with a qualitative synthesis. SETTINGS AND PARTICIPANTS: Older adults residing within residential aged care (otherwise referred to as nursing homes or long-term care). METHODS: The protocol was prospectively registered on PROSPERO (Reg. No.: CRD42022372036) using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Five electronic databases were searched from inception to November 23, 2023, with alerts monitored until March 28, 2024. Quality of studies was assessed using the ROB 2 and ROBIN-1 tools. RESULTS: A total of 10,955 articles were retrieved; 62 full articles were reviewed, with 3 studies included (2 randomized controlled trials and 1 nonrandomized controlled trial) involving 1030 participants. Included studies did not use specific frailty scores but reported individual components of frailty such as weight loss or number of medications prescribed. No trial combining medication review, exercise, and nutrition was identified. Medication review reduced the number of medications prescribed, whereas the use of nutritional support reduced gastrointestinal medication and maintained weight. CONCLUSION AND IMPLICATIONS: There is no published research investigating best-practice guidelines for medication optimization used in combination with both exercise and nutrition in aged care to address frailty. This review confirms the need for studies implementing Consensus Guidelines for frailty treatment in this vulnerable cohort.

The Frailty Reduction via Implementation of Exercise, Nutrition, and Deprescribing (FRIEND) Trial: Study Protocol and Recruitment Results.

INTRODUCTION: Virtually all adults in aged care facilities are frail, a condition which contributes to falls, cognitive decline, hospitalisation, and mortality. Polypharmacy, malnutrition, sedentariness, and sarcopenia are risk factors amenable to intervention. The Asia-Pacific Frailty Management Guidelines recommend anabolic exercise and the optimisation of medications and nutrition. However, no study has evaluated this best practice intervention triad in aged care. METHODS: The Frailty Reduction via the Implementation of Exercise, Nutrition, and Deprescribing (FRIEND) Trial (ANZCTR No.ACTRN12622000926730p) is a staged 6-month translational trial evaluating resident outcomes, staff/caregiver knowledge, and institutional implementation in a Townsville aged care facility. Residents received high-intensity resistance exercise and balance training and medication and nutrition optimisation co-implemented by investigators (exercise physiologist, geriatrician, pharmacist, and nutritionist) and facility staff. Staff and caregivers completed comprehensive education modules and training. We report the trial protocol and recruitment results. RESULTS: 29 residents (21 female, age: 88.6 ± 6.3 years) were recruited. At baseline, the residents were frail (frailty scale nursing home (FRAIL-NH); 6.3 ± 2.4/14), cognitively impaired (Montreal Cognitive Assessment; 13.8 ± 6.8/30), functionally impaired (Short Physical Performance Battery; 4.9 ± 3.1/12, 6 min walk distance; 222.2 ± 104.4 m), and were prescribed numerous medications (15.5 ± 5.9). Two residents died and one withdrew before the intervention's commencement. Thirty family members and 19 staff (carers, allied health assistants, nurse managers, registered nurses, lifestyle-leisure officers, kitchen/hospitality staff, and senior leadership) were recruited to receive frailty education modules. CONCLUSIONS: The FRIEND trial is currently being implemented with results expected in mid-2024. This is the first trial to evaluate the implementation of the best practice frailty guidelines including anabolic exercise and medication/nutritional optimisation in residential aged care.

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.

Effect of Brief Counseling by Allied Health Professionals on Step Count of People With Peripheral Artery Disease: A Randomized Clinical Trial.

Importance: It is unclear how to effectively promote walking in people with peripheral artery disease (PAD). Objective: To test whether brief counseling delivered by allied health professionals increases step count in participants with PAD. Design, Setting, and Participants: In this randomized clinical trial, participants with symptomatic PAD were recruited from sites in Australia and randomly allocated 1:1 to the counseling intervention or an attention control. Data were collected from January 2015 to July 2021, and data were analyzed from March to November 2022. Interventions: Two 1-hour face-to-face and two 15-minute telephone counseling sessions designed to increase walking. Main Outcomes and Measures: The primary outcome was the between-group difference in change in daily step count estimated by accelerometer recordings over 7 days at baseline and 4 months, using imputation for missing values. Other outcomes at 4, 12, and 24 months included step count, 6-minute walk distance, and disease-specific and generic measures of health-related quality of life. Risk of major adverse limb events was assessed over 24 months. Results: Of 200 included participants, 144 (72.0%) were male, and the mean (SD) age was 69.2 (9.3) years. The planned sample of 200 participants was allocated to the counseling intervention group (n = 102) or attention control group (n = 98). Overall, 198 (99.0%), 175 (87.5%), 160 (80.0%) and 143 (71.5%) had step count assessed at entry and 4, 12, and 24 months, respectively. There was no significant between-group difference in the primary outcome of change in daily step count over 4 months (mean steps, 415; 95% CI, -62 to 893; P = .07). Participants in the counseling group had significantly greater improvement in the secondary outcome of disease-specific Intermittent Claudication Questionnaire score at 4 months (3.2 points; 95% CI, 0.1-6.4; P = .04) and 12 months (4.3 points; 95% CI, 0.5-8.1; P = .03) but not at 24 months (1.2 points; 95% CI, -3.1 to 5.6; P = .57). Findings were similar for mean PAD Quality of Life Questionnaire component assessing symptoms and limitations in physical functioning (4 months: 1.5 points; 95% CI, 0.3-2.8; P = .02; 12 months: 1.8 points; 95% CI, 0.3-3.3; P = .02; 24 months: 1.3 points; 95% CI. -0.5 to 3.1; P = .16). There was no significant effect of the intervention on change in mean 6-minute walking distance (4 months: 9.3 m; 95% CI, -3.7 to 22.3; P = .16; 12 months: 13.8 m; 95% CI, -4.2 to 31.7; P = .13; 24 months: 1.2 m; 95% CI, -20.0 to 22.5; P = .91). The counseling intervention did not affect the rate of major adverse limb events over 24 months (12 [6.0%] in the intervention group vs 11 [5.5%] in the control group; P > .99). Conclusions and Relevance: This randomized clinical trial found no significant effect of brief counseling on step count in people with PAD. Alternate interventions are needed to enable walking. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12614000592640.

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.

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.

Effects of olives and their constituents on the expression of ulcerative colitis: a systematic review of randomised controlled trials.

Extra virgin olive oil is often associated with anti-inflammatory and antioxidant properties. Its effects on inflammatory conditions such as ulcerative colitis (UC), however, have yet to be defined. As such, we aimed to conduct a systematic review and meta-analysis of studies investigating olive-based interventions in UC. A comprehensive database search for randomised controlled trials was performed between 9 July 2018 and 16 August 2018. Studies identified from search alerts were included up to 22 June 2020. Both individuals living with UC at any disease stage and murine models of UC were included in this review. No human trials meeting the eligibility criteria were identified, while nineteen animal studies comprised 849 murine models of UC were included in this review. Pooling of the data could not be performed due to heterogeneous outcomes; however, general trends favouring olive-based interventions were identified. Milder disease expression including weight maintenance, reduced rectal bleeding and well-formed stools favouring olive-based interventions was statistically significant in 16/19 studies, with moderate-to-large effect sizes (-0·66 (95 % CI -1·56, 0·24) to -12·70 (95 % CI -16·8, -8·7)). Olive-based interventions did not prevent the development of colitis-like pathologies in any study. In conclusion, effects of olive-based interventions on murine models of UC appear promising, with milder disease outcomes favouring the intervention in most trials and effect sizes suggesting potential clinical relevance. However, the lack of published randomised controlled human trials warrants further investigation to determine if these effects would translate to individuals living with UC.

The Long-term Effect of Different Exercise Intensities on High-Density Lipoprotein Cholesterol in Older Men and Women Using the Per Protocol Approach: The Generation 100 Study.

OBJECTIVE: To examine whether 5 years of high-intensity interval training (HIIT) increases high-density lipoprotein cholesterol (HDL-C) concentration more than moderate-intensity continuous training (MICT) and control (CON) in older men and women. METHODS: A total of 1567 older adults (790 [50.4%] women) were randomized (2:1:1) to either CON (n=780; asked to follow the national recommendations for physical activity) or 2 weekly sessions of HIIT (10-minute warm-up followed by 4×4-minute intervals at ∼90% of peak heart rate) or MICT (50 minutes of continuous work at ∼70% of peak heart rate). Serum HDL-C concentration was measured by standard procedures at baseline and at 1 year, 3 years, and 5 years. The study took place between August 21, 2012, and June 31, 2018. Linear mixed models were used to determine between-group differences during 5 years using the per protocol approach. RESULTS: Men in HIIT had a smaller reduction in HDL-C (-1.2%) than men in CON (-6.9%) and MICT (-7.8%) after 5 years (P=.01 and P=.03 for CON vs HIIT and MICT vs HIIT, respectively). No effect of exercise intensity on HDL-C was seen in women. Changes in peak oxygen uptake were associated with changes in HDL-C in both men and women, whereas changes in body weight and fat mass were not. CONCLUSION: In men, HIIT seems to be the best strategy to prevent a decline in HDL-C during a 5-year period. No effect of exercise intensity was seen for older women. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01666340.

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.

Impact of adiposity on clinical outcomes in people living with a Fontan circulation.

BACKGROUND: To assess the association between body composition and the risk of adverse outcomes in Fontan patients. METHODS: Participants from the Australian and New Zealand Fontan Registry with dual-energy X-ray absorptiometry scans were included. Appendicular lean mass (ALM), appendicular lean mass index (ALM divided by height squared; ALMI) and total body fat mass percentage (%BF) were calculated. ALMI and %BF z-scores were derived using age- and sex-matched reference ranges. The primary outcome was Fontan failure (death, transplantation, New York Heart Association functional class III/IV, protein-losing enteropathy, and plastic bronchitis) or moderate-or-severe ventricular dysfunction. RESULTS: 144 patients were included. Mean %BF was 29% (SD 10) with 50% having increased adiposity. Mean ALMI z-score was -1.4 (SD 1.1); one third of patients had skeletal muscle deficiency (ALMI z-score < -1 and -2) and another third had Fontan-associated myopaenia (ALMI z-score < -2). Age and %BF were associated with the risk of the endpoint in univariable regression (age: HR 1.09 per year, 95% CI 1.02-1.17, p = 0.01; %BF: HR 1.08, 95% CI 1.01-1.17, p = 0.03). On multivariable regression, every 1% increase in %BF was associated with a 10% increased risk of reaching the clinical endpoint (HR 1.10, 95% CI 1.01-1.19; p = 0.03). ALM was not associated with the endpoint (HR 1.02 per kg, 95% CI 0.88-1.20, p = 0.77). CONCLUSIONS: Increased adiposity is associated with higher risk for adverse outcomes. Prospective studies to assess lifestyle interventions to optimise body composition should be prioritised.

Effect of exercise training for five years on all cause mortality in older adults-the Generation 100 study: randomised controlled trial.

OBJECTIVE: To evaluate the effect of five years of supervised exercise training compared with recommendations for physical activity on mortality in older adults (70-77 years). DESIGN: Randomised controlled trial. SETTING: General population of older adults in Trondheim, Norway. PARTICIPANTS: 1567 of 6966 individuals born between 1936 and 1942. INTERVENTION: Participants were randomised to two sessions weekly of high intensity interval training at about 90% of peak heart rate (HIIT, n=400), moderate intensity continuous training at about 70% of peak heart rate (MICT, n=387), or to follow the national guidelines for physical activity (n=780; control group); all for five years. MAIN OUTCOME MEASURE: All cause mortality. An exploratory hypothesis was that HIIT lowers mortality more than MICT. RESULTS: Mean age of the 1567 participants (790 women) was 72.8 (SD 2.1) years. Overall, 87.5% of participants reported to have overall good health, with 80% reporting medium or high physical activity levels at baseline. All cause mortality did not differ between the control group and combined MICT and HIIT group. When MICT and HIIT were analysed separately, with the control group as reference (observed mortality of 4.7%), an absolute risk reduction of 1.7 percentage points was observed after HIIT (hazard ratio 0.63, 95% confidence interval 0.33 to 1.20) and an absolute increased risk of 1.2 percentage points after MICT (1.24, 0.73 to 2.10). When HIIT was compared with MICT as reference group an absolute risk reduction of 2.9 percentage points was observed (0.51, 0.25 to 1.02) for all cause mortality. Control participants chose to perform more of their physical activity as HIIT than the physical activity undertaken by participants in the MICT group. This meant that the controls achieved an exercise dose at an intensity between the MICT and HIIT groups. CONCLUSION: This study suggests that combined MICT and HIIT has no effect on all cause mortality compared with recommended physical activity levels. However, we observed a lower all cause mortality trend after HIIT compared with controls and MICT. TRIAL REGISTRATION: ClinicalTrials.gov NCT01666340.

A missense mutation in the MLKL brace region promotes lethal neonatal inflammation and hematopoietic dysfunction.

MLKL is the essential effector of necroptosis, a form of programmed lytic cell death. We have isolated a mouse strain with a single missense mutation, MlklD139V, that alters the two-helix 'brace' that connects the killer four-helix bundle and regulatory pseudokinase domains. This confers constitutive, RIPK3 independent killing activity to MLKL. Homozygous mutant mice develop lethal postnatal inflammation of the salivary glands and mediastinum. The normal embryonic development of MlklD139V homozygotes until birth, and the absence of any overt phenotype in heterozygotes provides important in vivo precedent for the capacity of cells to clear activated MLKL. These observations offer an important insight into the potential disease-modulating roles of three common human MLKL polymorphisms that encode amino acid substitutions within or adjacent to the brace region. Compound heterozygosity of these variants is found at up to 12-fold the expected frequency in patients that suffer from a pediatric autoinflammatory disease, chronic recurrent multifocal osteomyelitis (CRMO).

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.

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.

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.

Promoting independence in Lewy body dementia through exercise (PRIDE) study: Protocol for a pilot study.

BACKGROUND: Lewy Body dementia (LBD) is the second most prevalent neurodegenerative dementia. This form of dementia is notable for an aggressive disease course consisting of a combination of cognitive, Parkinsonian, affective, and physiological symptoms that significantly increase morbidity and mortality, and decrease life expectancy in this population compared to more common dementias. Additionally, those diagnosed with LBD are often excluded from trials evaluating exercise in similar diseases such as Alzheimer's disease or Parkinson's disease due to the complexity and concurrency of motor and cognitive symptoms. Consequently, there is scarce research evaluating the effect of exercise on individuals with LBD. METHODS: The PRomoting Independence in Lewy Body Dementia through Exercise (PRIDE) trial is a novel non-randomised, crossover pilot study consisting of an 8-week wait-list usual care period, followed by an 8-week exercise intervention targeting progressive resistance and balance training. The trial aim is to evaluate the effect of exercise on the primary outcome of functional independence and secondary outcomes including cognitive, physical, psychosocial and quality of life measures in people living with LBD and their caregivers. The intervention involves 3 supervised 1-h sessions per week (24 sessions in total) administered by an Accredited Exercise Physiologist in a clinical facility at the University of Sydney in Lidcombe, Australia. DISCUSSION: The PRIDE study is the first controlled trial to evaluate a robust exercise intervention within a LBD cohort and will provide crucial information required to inform robust future clinical trials. TRIAL REGISTRATION: Australia and New Zealand Trial Register (ANZCTR): ACTRN12616000466448; Key words: Lewy body; dementia; exercise; anabolic; functional independence.

Design and Development of the Brain Training System for the Digital "Maintain Your Brain" Dementia Prevention Trial.

BACKGROUND: Dementia is the leading cause of disability worldwide, and interventions aimed at reducing the prevalence and burden of the disease are urgently needed. Maintain Your Brain (MYB) is a randomized controlled trial of a multimodal digital health intervention targeting modifiable dementia risk factors to combat cognitive decline and potentially prevent dementia. In addition to behavioral modules targeting mood, nutrition, and physical exercise, a new Brain Training System (BTS) will deliver computerized cognitive training (CCT) throughout the trial to provide systematic, challenging, and personally adaptive cognitive activity. OBJECTIVE: This paper aimed to describe the design and development of BTS. METHODS: BTS has been designed with a central focus on the end user. Raw training content is provided by our partner NeuroNation and delivered in several innovative ways. A baseline cognitive profile directs selection and sequencing of exercises within and between sessions and is updated during the 10-week 30-session module. Online trainers are available to provide supervision at different levels of engagement, including face-to-face share-screen coaching, a key implementation resource that is triaged by a "red flag" system for automatic tracking of user adherence and engagement, or through user-initiated help requests. Individualized and comparative feedback is provided to aid motivation and, for the first time, establish a social support network for the user based on their real-world circle of friends and family. RESULTS: The MYB pilot was performed from November 2017 to March 2018. We are currently analyzing data from this pilot trial (n=100), which will make up a separate research paper. The main trial was launched in June 2018. Process and implementation data from the first training module (September to November 2018) are expected to be reported in 2019 and final trial outcomes are anticipated in 2022. CONCLUSIONS: The BTS implemented in MYB is focused on maximizing adherence and engagement with CCT over the short and long term in the setting of a fully digital trial, which, if successful, could be delivered economically at scale. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618000851268; https://www.anzctr.org.au /Trial/Registration/TrialReview.aspx?id=370631&isReview=true.

Maintain Your Brain: Protocol of a 3-Year Randomized Controlled Trial of a Personalized Multi-Modal Digital Health Intervention to Prevent Cognitive Decline Among Community Dwelling 55 to 77 Year Olds.

BACKGROUND: Maintain Your Brain (MYB) is a randomized controlled trial of an online multi-modal lifestyle intervention targeting modifiable dementia risk factors with its primary aim being to reduce cognitive decline in an older age cohort. METHODS: MYB aims to recruit 8,500 non-demented community dwelling 55 to 77 year olds from the Sax Institute's 45 and Up Study in New South Wales, Australia. Participants will be screened for risk factors related to four modules that comprise the MYB intervention: physical activity, nutrition, mental health, and cognitive training. Targeting risk factors will enable interventions to be personalized so that participants receive the most appropriate modules. MYB will run for three years and up to four modules will be delivered sequentially each quarter during year one. Upon completing a module, participants will continue to receive less frequent booster activities for their eligible modules (except for the mental health module) until the end of the trial. DISCUSSION: MYB will be the largest internet-based trial to attempt to prevent cognitive decline and potentially dementia. If successful, MYB will provide a model for not just effective intervention among older adults, but an intervention that is scalable for broad use.