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

Preliminary evidence that low ankle-brachial index is associated with reduced bilateral hip extensor strength and functional mobility in peripheral arterial disease

ObjectivePeripheral arterial disease (PAD) has been associated with skeletal muscle pathology, including atrophy of the affected muscles. In addition, oxidative metabolism is impaired, muscle function is reduced, and gait and mobility are restricted. We hypothesized that greater severity of symptomatic PAD would be associated with lower levels of muscle mass, strength, and endurance, and that these musculoskeletal abnormalities in turn would impair functional performance and walking ability in patients with PAD.MethodsWe assessed 22 persons with intermittent claudication from PAD in this cross-sectional pilot study. Outcome assessments included initial claudication distance and absolute claudication distance via treadmill protocols and outcomes from the 6-minute walk (6MW). Secondary outcomes included one repetition maximum strength/endurance testing of hip extensors, hip abductors, quadriceps, hamstrings, plantar flexors, pectoral, and upper back muscle groups, as well as performance-based tests of function. Univariate and stepwise multiple regression models were constructed to evaluate relationships and are presented.ResultsTwenty-two participants (63.6% male; mean [standard deviation] age, 73.6 [8.2] years; range, 55-85 years) were studied. Mean (standard deviation) resting ankle-brachial index (ABI) was 0.54 ([0.13]; range, 0.28-0.82), and participants ranged from having mild claudication to rest pain. Lower resting ABI was significantly associated with reduced bilateral hip extensor strength (r = 0.54; P = .007) and reduced whole body strength (r = 0.32; P = .05). In addition, lower ABI was associated with a shorter distance to first stop during the 6MW (r = 0.38; P = .05) and poorer single leg balance (r = 0.44; P = .03). Reduced bilateral hip extensor strength was also significantly associated with functional outcomes, including reduced 6MW distance to first stop (r = 0.74; P = .001), reduced 6MW distance (r = 0.75; P < .001), and reduced total short physical performance battery score (worse function; r = 0.75; P = .003).ConclusionsOur results suggest the existence of a causal pathway from a reduction in ABI to muscle atrophy and weakness, to whole body disability represented by claudication outcomes and performance-based tests of functional mobility in an older cohort with symptomatic PAD. Longitudinal outcomes from this study and future trials are required to investigate the effects of an anabolic intervention targeting the muscles involved in mobility and activities of daily living and whether an increase in muscle strength will improve symptoms of claudication and lead to improvements in other functional outcomes in patients with PAD

A case study of an 87-year-old male bodybuilder with complex health conditions

This exploratory clinical case report presents an 87-year-old man who began bodybuilding at the age of 76 years and was officially recognised as the world’s oldest competitive bodybuilder, competing until age 83. He has a background of complex health conditions including polio, strokes, cardiac arrest, atrial fibrillation, prostate disease, osteoarthritis, depression, bowel obstruction, reflux, and bladder cancer. Assessments of body composition, bone density, muscle performance, and diet-related practices were performed. The bodybuilder had superior fat-free mass, lower fat mass, and generally greater muscle performance compared to untrained healthy males of a similar age. Commencement of bodybuilding in older age appears to be possible, even with ongoing complex health conditions, and the potential benefits of this practice require systematic investigation in the future

A Randomized Controlled Trial of Whole Body Vibration Exposure on Markers of Bone Turnover in Postmenopausal Women

Purpose. To examine the effects of two doses of low-frequency (12 Hz), low-magnitude (0.3 g), whole body vibration on markers of bone formation and resorption in postmenopausal women. Methods. Women were recruited and randomized into a sham vibration control group, one time per week vibration group (1×/week), or three times per week vibration group (3×/week). Vibration exposure consisted of 20 minutes of intermittent vibration for the 1×/week and 3×/week groups, and sham vibration (<0.1 g) for the control group for eight weeks. Double-blinded primary outcome measures were urine markers of bone resorption: N-telopeptide X normalised to creatinine (NTx/Cr) and bone formation: bone-specific alkaline phosphatase (ALP). Results. Forty-six women (59.8 ± 6.2 years, median 7.3 years since menopause) were enrolled. NTx/Cr was significantly reduced (34.6%) in the 3×/wk vibration group but not in the 1×/wk vibration group compared with sham control (P < .01) group. No effect of time or group allocation was observed on the bone formation marker ALP (P = .27). Conclusion. We have shown for the first time that low-frequency, low-magnitude vibration 3×/week for eight weeks in postmenopausal women results in a significant reduction in NTx/Cr, a marker of bone resorption, when compared with sham vibration exposure

Reductions in C-reactive protein in older adults with type 2 diabetes are related to improvements in body composition following a randomized controlled trial of resistance training

BACKGROUND: Reductions in skeletal muscle mass and increased adiposity are key elements in the aging process and in the pathophysiology of several chronic diseases. Systemic low grade inflammation associated with obesity has been shown to accelerate the age-related decline in skeletal muscle. The aim of this investigation was to determine the effects of 12 months of progressive resistance training (PRT) on systemic inflammation, and whether reductions in systemic inflammation were associated with changes in body composition. We hypothesized that reductions in systemic inflammation following 12 months of PRT in older adults with type 2 diabetes would be associated with reductions in adiposity and increases in skeletal muscle mass. METHODS: Participants (n = 103) were randomized to receive either PRT or sham-exercise, 3 days a week for 12 months. C-reactive protein (CRP) was used to assess systemic inflammation. Skeletal muscle mass and total fat mass were determined using bioelectrical impedance. RESULTS: Twelve months of PRT tended to reduce CRP compared to sham exercise (β = −0.25, p = 0.087). Using linear mixed-effects models, the hypothesized relationships between body composition adaptations and CRP changes were significantly stronger for skeletal muscle mass (p = 0.04) and tended to be stronger for total fat mass (p = 0.07) following PRT when compared to sham-exercise. Using univariate regression models, stratified by group allocation, reductions in CRP were associated with increases in skeletal muscle mass (p = 0.01) and reductions in total fat mass (p = 0.02) in the PRT group, but not in the sham-exercise group (p = 0.87 and p = 0.32, respectively). CONCLUSIONS: We have shown for the first time that reductions in systemic inflammation in older adults with type 2 diabetes following PRT were associated with increases in skeletal muscle mass. Furthermore, reductions in CRP were associated with reductions in adiposity, but only when associated with PRT. Lifestyle interventions aimed at reducing systemic inflammation in older adults with type 2 diabetes should therefore incorporate anabolic exercise such as PRT to optimize the anti-inflammatory benefits of favorable body composition adaptations

Genomewide association study of acute anterior uveitis identifies new susceptibility loci

Acknowledgments The authors thank all participating subjects with AS and healthy individuals who provided the DNA and clinical information necessary for this study. We would like to acknowledge the contributions of Anna Deminger, Sahlgrenska Academy at University of Gothenburg, and Urban Hellman, Umeå University, for their assistance in case recruitment and assessment and handling biological samples Funding Information: The survey was conducted by NatCen and the genomewide scan data were analyzed and deposited by the Wellcome Trust Sanger Institute. Information on how to access the data can be found on the Understanding Society website https: www. understandingsociety.ac.uk/ . We acknowledge and thank the TCRA AS Group for their support in recruiting patients for the study. M.A.B. is funded by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship, and support for this study was received from a National Health and Medical Research Council (Australia) program Grant (566938) and project Grant (569829), and from the Australian Cancer Research Foundation and Rebecca Cooper Medical Research Foundation. We are also very grateful for the invaluable support received from the National Ankylosing Spondylitis Society (UK) and Spondyloarthritis Association of America in case recruitment. Additional financial and technical support for patient recruitment was provided by the National Institute for Health Research Oxford Musculoskeletal Biomedical Research Unit and NIHR Thames Valley Comprehensive Local Research and an unrestricted educational grant from Abbott Laboratories. The authors acknowledge the sharing of data and samples by the BSRBR-AS Register in Aberdeen. Chief Investigator, Prof Gary Macfarlane and Dr Gareth Jones, Deputy Chief Investigator, created the BSRBR-AS study, which was commissioned by the British Society for Rheumatology, funded in part by Abbvie, Pfizer, and UCB. We are grateful to every patient, past and present staff of the BSRBR-AS register team, and to all clinical staff who recruited patients, followed them up and entered data – details here: https://www.abdn.ac.uk/iahs/research/ epidemiology/spondyloarthritis.php#panel1011. Funding was also received from the Swedish Research Council and The Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement. The Irish data was derived from participants in ASRI – The Ankylosing Spondylitis Registry of Ireland, which is funded by unrestricted grants from Abbvie and Pfizer. Funding bodies involved played no role in the study design, performance, or preparation of this manuscript. Funding Information: X.F.H. was funded by the National Natural Science Foundation of China (31771390). The TASC study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grants P01-052915, R01-AR046208. Funding was also received from the University of Texas Health Science Center at Houston CTSA grant UL1RR02418, Cedars-Sinai GCRC grant MO1-RR00425, Intramural Research Program, NIAMS/NIH, and Rebecca Cooper Foundation (Australia). This study was funded, in part, by Arthritis Research UK (Grants 19536 and 18797), by the Wellcome Trust (Grant number 076113), and by the Oxford Comprehensive Biomedical Research Centre ankylosing spondylitis chronic disease cohort (Theme Code: A91202). The New Zealand data was derived from participants in the Spondyloarthritis Genetics and the Environment Study (SAGE) and was funded by The Health Research Council, New Zealand. H.X. was funded by the National Natural Science Foundation of China Grant 81020108029 and 30872339. French sample collection was performed by the Groupe Française d’Etude Génétique des Spondylarthrites, coordinated by Professor Maxime Breban, and funded by the Agence Nationale de Recherche GEMISA grant reference ANR-10-MIDI-0002. We acknowledge the Understanding Society: The UK Household Longitudinal Study. This is led by the Institute for Social and Economic Research at the University of Essex and funded by the Economic and Social Research Council. Publisher Copyright: © 2020 Association for Research in Vision and Ophthalmology Inc.. All rights reserved.Peer reviewedPublisher PD

Cognitive and memory training in adults at risk of dementia: A Systematic Review

<p>Abstract</p> <p>Background</p> <p>Effective non-pharmacological cognitive interventions to prevent Alzheimer's dementia or slow its progression are an urgent international priority. The aim of this review was to evaluate cognitive training trials in individuals with mild cognitive impairment (MCI), and evaluate the efficacy of training in memory strategies or cognitive exercises to determine if cognitive training could benefit individuals at risk of developing dementia.</p> <p>Methods</p> <p>A systematic review of eligible trials was undertaken, followed by effect size analysis. Cognitive training was differentiated from other cognitive interventions not meeting generally accepted definitions, and included both cognitive exercises and memory strategies.</p> <p>Results</p> <p>Ten studies enrolling a total of 305 subjects met criteria for cognitive training in MCI. Only five of the studies were randomized controlled trials. Meta-analysis was not considered appropriate due to the heterogeneity of interventions. Moderate effects on memory outcomes were identified in seven trials. Cognitive exercises (relative effect sizes ranged from .10 to 1.21) may lead to greater benefits than memory strategies (.88 to -1.18) on memory.</p> <p>Conclusions</p> <p>Previous conclusions of a lack of efficacy for cognitive training in MCI may have been influenced by not clearly defining the intervention. Our systematic review found that cognitive exercises can produce moderate-to-large beneficial effects on memory-related outcomes. However, the number of high quality RCTs remains low, and so further trials must be a priority. Several suggestions for the better design of cognitive training trials are provided.</p

Effect of standing posture during whole body vibration training on muscle morphology and function in older adults: A randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Whole body vibration (WBV) is a novel modality of exercise shown to improve musculoskeletal function. This study aims to examine the effects of standing posture during low magnitude WBV training on muscle function and muscle morphology in older adults.</p> <p>Methods</p> <p>Nineteen men and women (50-80 years) were recruited to a three month randomised controlled trial and allocated to one of three groups: WBV with flexed knees (FK), WBV with locked knees (LK), or sham WBV with flexed knees (CON). Exposure was intermittent (1 min WBV:1 min rest) for 20 min, three times per week for 13 weeks. Measurements were taken at baseline and at three months. Primary outcomes included upper and lower body muscle function (strength, power and velocity). Secondary outcomes were muscle morphology, balance, habitual and maximal gait velocity, stair climb power, and chair stand performance.</p> <p>Results</p> <p>Sixteen subjects completed the study. Relative (%) upper body contraction velocity improved significantly after WBV with FK compared to LK (FK 16.0%, LK -7.6%, CON 4.7, p = 0.01). Relative upper body strength (LK 15.1%, p = 0.02; FK 12.1%, p = 0.04; CON 4.7%) increased significantly following WBV compared to control. Absolute (p = 0.05) and relative (p = 0.03) lower leg strength significantly improved with both standing postures (LK 14.4%; FK 10.7%; CON 1.3%). Only the LK group differed significantly from CON in relative leg strength gains (p = 0.02). Potentially clinically meaningful but statistically non-significant improvements in lower leg muscle cross-sectional area (LK 3.7 cm², FK 2.4 cm², CON 2.2 cm²p = 0.13) were observed after WBV with LK compared to the other groups. No significant effects of WBV on any functional performance tests were observed.</p> <p>Conclusions</p> <p>Our results suggest that WBV may improve muscle strength and contraction velocity in some muscle groups in older adults. However, hypothesised differential adaptation to standing posture (FK > LK) was observed only for upper body contraction velocity, making recommendations regarding this prescriptive element inconclusive. The efficacy, mechanism of action and long term feasibility of WBV for musculoskeletal health in older adults warrants continued investigation in robustly designed, sufficiently powered future studies.</p> <p>Trial Registration</p> <p>ACTRN12609000353291.</p