PREVENTING LOSS OF INDEPENDENCE THROUGH EXERCISE (PLIE) AND PAIRED PLIE: RESULTS TO DATE
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SUBMITTER: Barnes D
PROVIDER: S-EPMC6239823 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
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Project description:BackgroundCurrent dementia medications have small effect sizes, many adverse effects and do not change the disease course. Therefore, it is critically important to study alternative treatment strategies. The goal of this study was to pilot-test a novel, integrative group exercise program for individuals with mild-to-moderate dementia called Preventing Loss of Independence through Exercise (PLIÉ), which focuses on training procedural memory for basic functional movements (e.g., sit-to-stand) while increasing mindful body awareness and facilitating social connection.MethodsWe performed a 36-week cross-over pilot clinical trial to compare PLIÉ with usual care (UC) at an adult day program for individuals with dementia in San Francisco, CA. Assessments of physical performance, cognitive function, physical function, dementia-related behaviors, quality of life and caregiver burden were performed by blinded assessors at baseline, 18 weeks (cross-over) and 36 weeks. Our primary outcomes were effect sizes based on between-group comparisons of change from baseline to 18 weeks; secondary outcomes were within-group comparisons of change before and after cross-over.ResultsTwelve individuals enrolled (7 PLIÉ, 5 UC) and 2 withdrew (1 PLIÉ, 18 weeks; 1 UC, 36 weeks). Participants were 82% women (mean age, 84 ± 4 years); caregivers were 82% daughters (mean age, 56 ± 13 years). Effect sizes were not statistically significant but suggested potentially clinically meaningful (≥ 0.25 SDs) improvement with PLIÉ versus UC for physical performance (Cohen's D: 0.34 SDs), cognitive function (0.76 SDs) and quality of life (0.83 SDs) as well as for caregiver measures of participant's quality of life (0.33 SDs) and caregiver burden (0.49 SDs). Results were similar when within-group comparisons were made before and after cross-over.ConclusionsPLIÉ is a novel, integrative exercise program that shows promise for improving physical function, cognitive function, quality of life and caregiver burden in individuals with mild-to-moderate dementia. Larger randomized, controlled trials are warranted.Trial registrationClinicalTrials.gov NCT01371214.
| S-EPMC4324943 | biostudies-literature
Project description:BackgroundPreventing Loss of Independence through Exercise (PLIÉ) is a group movement program initially developed for people with mild-to-moderate dementia that integrates principles from several well-established traditions to specifically address the needs of people with cognitive impairment.ObjectiveTo investigate whether PLIÉ would benefit cognitive and behavioral outcomes and functional brain connectivity in older adults with milder forms of cognitive impairment.MethodsParticipants (≥55 y) with subjective memory decline (SMD) or mild cognitive impairment (MCI) were assessed with tests of cognitive and physical function, self-report questionnaires, and resting state functional magnetic resonance imaging (rs-fMRI) on a 3 Tesla scanner before and after participating in twice weekly PLIÉ classes for 12 weeks at the San Francisco Veterans Affairs Medical Center.ResultsEighteen participants completed the pre-post intervention pilot trial. We observed significant improvements on the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog; effect size 0.34, p = 0.002) and enhanced functional connections between the medial prefrontal cortex (mPFC) and other nodes of the default mode network (DMN) after PLIÉ. Improvements (i.e., lower scores) on ADAS-cog were significantly correlated with enhanced functional connectivity between the mPFC and left lateral parietal cortex (Spearman's ρ= -0.74, p = 0.001) and between the mPFC and right hippocampus (Spearman's ρ= -0.83, p = 0.001). After completing PLIÉ, participants reported significant reductions in feelings of social isolation and improvements in well-being and interoceptive self-regulation.ConclusionThese preliminary findings of post-PLIÉ improvements in DMN functional connectivity, cognition, interoceptive self-regulation, well-being and reduced feelings of social isolation warrant larger randomized, controlled trials of PLIÉ in older adults with SMD and MCI.
| S-EPMC8461710 | biostudies-literature
Project description:BackgroundLewy 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.MethodsThe 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.ResultsNine 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.ConclusionsPRIDE 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 registrationThe PRIDE trial protocol has previously been prospectively registered (08/04/2016, ANZCTR: ACTRN12616000466448).
| S-EPMC9361699 | biostudies-literature
Project description:Background and objectivesUnderstanding how older people experience independence has implications for person-centered care. Existing understanding of older people's experience of independence, generated through methods that provide a "snapshot" view of a person's independence at a given time point, provides little insight into the process of maintaining independence through time. The aim of this study was to explore older participants' perceptions to understand the processes and resources that were most important for maintaining independence.Research design and methodsTwo semistructured interviews were conducted longitudinally to explore the perspectives of 12 community-dwelling, older people, aged 76-85 years. A social constructivist approach, using dramaturgical and descriptive codes, facilitated the interpretation of the data. Sixteen analytical questions guided the exploration of participants' perceptions of independence through time.ResultsOlder people suggested that objective representations underestimated, and omitted, important aspects of their independence through time. Some participants perceived "snapshot" judgments of their independence as insensitive to their individual values and context. Change over time required some participants to adapt their methods for maintaining independence. The stability of participants' sense of independence was value dependent and informed by the purpose a participant ascribed to maintaining independence.Discussion and implicationsThis study augments the understanding of independence as a complex and multifaceted construct. The findings challenge the congruence of common interpretations of independence with older people's views, showing areas of commonality, and discrepancy. Exploration of independence in terms of form and function provides an important understanding of how function takes precedence to form in determining the maintenance of independence through time.
| S-EPMC10825833 | biostudies-literature
Project description:Background and objectivesIt remains unknown whether the combination of antiresorptive agents and exercise would generate additive effects on bone mineral density (BMD) in postmenopausal women, though their separate roles in preventing bone loss have been well established. This meta-analysis aimed to evaluate the combined impact of antiresorptive treatment and exercise on the lumbar spine and femoral neck BMD in postmenopausal women compared with an exercise-only intervention.MethodsA systematic literature search of PubMed, EMBASE, SportDiscus and ProQuest up to Jun 2014 was conducted to identify the influence of antiresorptive agents and exercise on BMD in postmenopausal women. The study quality of the included trials was evaluated. The effect sizes were estimated by calculating the standardized mean difference (SMD). Subgroup analyses were conducted by pharmacological regimens and exercise categories.ResultsNine studies with a total of 1,248 postmenopausal women met the inclusion criteria. The heterogeneity between the studies was evident at the spine (I² = 78.7%) and hip (I² = 41.7%) measurements; random-effects models were used in the data analysis. The pooled effect sizes associated with the combined interventions of antiresorptive agents and exercise were significant at the lumbar spine BMD (SMD = 0.511, 95% CI = 0.118-0.904, p = 0.011). Combining hormone replacement therapy (HRT) and exercise training generated greater beneficial effects on lumbar spine (SMD = 0.729, 95% CI = 0.186-1.273, p = 0.009) and femoral neck BMD (SMD = 0.220, 95% CI = 0.0110-429, p = 0.039) than the exercise-only intervention. Impact exercise was sensitive to antiresorptive agents in preventing postmenopausal bone loss both at the spine (SMD = 1.252, 95%CI = 0.465-2.039, p = 0.002) and hips (SMD = 0.414, 95%CI = 0.106-0.723, p = 0.008).ConclusionsOur findings indicate that antiresorptive agents significantly increase the impact of exercise on the prevention of bone loss in postmenopausal women, which implies that the combination of antiresorptive agents and exercise may generate additive effects.
| S-EPMC4304813 | biostudies-literature
Project description:The polycomb protein MEL-18 has been proposed as a tumor suppressor in breast cancer; however, its functional relevance to the hormonal regulation of breast cancer remains unknown. Here, we demonstrated that MEL-18 loss contributes to the hormone-independent phenotype of breast cancer by modulating hormone receptor expression. In multiple breast cancer cohorts, MEL-18 was markedly downregulated in triple-negative breast cancer (TNBC). MEL-18 expression positively correlated with the expression of luminal markers, including estrogen receptor-? (ER-?, encoded by ESR1). MEL-18 loss was also associated with poor response to antihormonal therapy in ER-?-positive breast cancer. Furthermore, whereas MEL-18 loss in luminal breast cancer cells resulted in the downregulation of expression and activity of ER-? and the progesterone receptor (PR), MEL-18 overexpression restored ER-? expression in TNBC. Consistently, in vivo xenograft experiments demonstrated that MEL-18 loss induces estrogen-independent growth and tamoxifen resistance in luminal breast cancer, and that MEL-18 overexpression confers tamoxifen sensitivity in TNBC. MEL-18 suppressed SUMOylation of the ESR1 transactivators p53 and SP1, thereby driving ESR1 transcription. MEL-18 facilitated the deSUMOylation process by inhibiting BMI-1/RING1B-mediated ubiquitin-proteasomal degradation of SUMO1/sentrin-specific protease 1 (SENP1). These findings demonstrate that MEL-18 is a SUMO-dependent regulator of hormone receptors and suggest MEL-18 expression as a marker for determining the antihormonal therapy response in patients with breast cancer.
| S-EPMC4463188 | biostudies-literature
Project description:IntroductionThere are 3.9 million people in the UK with diabetes. Sarcopenia, increased frailty and loss of independence are often unappreciated complications of diabetes. Resistance exercise shows promise in reducing these complications in older adult diabetes patients. The aim of this feasibility randomised controlled trial is to (1) characterise the physical function, cardiovascular health and the health and well-being of older adults with mild frailty with/without diabetes treated with insulin, (2) to understand the feasibility and acceptability of a 4-week resistance exercise training programme in improving these parameters for those with diabetes and (3) to test the feasibility of recruiting and randomising the diabetic participant group to a trial of resistance training.Methods and analysisThirty adults aged ≥60 years with insulin-treated diabetes mellitus (type 1 or 2), and 30 without, all with mild frailty (3-4 on the Rockwood Frailty Scale) will be recruited. All will complete blood, cardiovascular and physical function testing. Only the diabetic group will then proceed into the trial itself. They will be randomised 1:1 to a 4-week semisupervised resistance training programme, designed to increase muscle mass and strength, or to usual care, defined as their regular physical activity, for 4 weeks. This group will then repeat testing. Primary outcomes include recruitment rate, attrition rate, intervention fidelity and acceptability, and adherence to the training programme. A subset of participants will be interviewed before and after the training programme to understand experiences of resistance training, impact on health and living with diabetes (where relevant) as they have aged. Analyses will include descriptive statistics and qualitative thematic analysis.Ethics and disseminationThe North East-Newcastle and North Tyneside 2 Research Ethics Committee (20/NE/0178) approved the study. Outputs will include feasibility data to support funding applications for a future definitive trial, conference and patient and public involvement presentations, and peer-reviewed publications.Trial registration numberISRCTN13193281.
| S-EPMC8655574 | biostudies-literature
Project description:Beneficial effects of resistance exercise on metabolic health and particularly muscle hypertrophy and fat loss are well established, but the underlying chemical and physiological mechanisms are not fully understood. Here we identified a myometabolite-mediated metabolic pathway that is essential for the beneficial metabolic effects of resistance exercise in mice. We showed that substantial accumulation of the tricarboxylic acid cycle intermediate ?-ketoglutaric acid (AKG) is a metabolic signature of resistance exercise performance. Interestingly, human plasma AKG level is also negatively correlated with BMI. Pharmacological elevation of circulating AKG induces muscle hypertrophy, brown adipose tissue (BAT) thermogenesis, and white adipose tissue (WAT) lipolysis in vivo. We further found that AKG stimulates the adrenal release of adrenaline through 2-oxoglutarate receptor 1 (OXGR1) expressed in adrenal glands. Finally, by using both loss-of-function and gain-of-function mouse models, we showed that OXGR1 is essential for AKG-mediated exercise-induced beneficial metabolic effects. These findings reveal an unappreciated mechanism for the salutary effects of resistance exercise, using AKG as a systemically-derived molecule for adrenal stimulation of muscle hypertrophy and fat loss.
| S-SCDT-EMBOJ-2019-103304 | biostudies-other
Project description:Ovarian cancer is the first cause of death from gynaecological malignancy. Germline mutation in BRCA1 and 2, two genes involved in the mechanisms of reparation of DNA damage, are showed to be related with the incidence of breast and ovarian cancer, both sporadic and familiar. PARP is a family of enzymes involved in the base excision repair (BER) system. The introduction of inhibitors of PARP in patients with BRCA-mutated ovarian cancer is correlated with the concept of synthetic lethality. Among the PARP inhibitors introduced in clinical practice, niraparib showed interesting results in a phase III trial in the setting of maintenance treatment in ovarian cancer, after platinum-based chemotherapy. Interestingly, was niraparib showed to be efficacious not only in BRCA-mutated patients, but also in patients with other alterations of the homologous recombination (HR) system and in patients with unknown alterations. These results position niraparib as the first PARP-inhibitor with clinically and statistically significant results also in patients with no alterations in BRCA 1/2 and other genes involved in the DNA repair system. Even if the results are potentially practice-changing, the action of niraparib must be further studied and deepened.
| S-EPMC5564880 | biostudies-literature
Project description:Prediabetes increases the risk for new-onset diabetes mellitus in patients receiving statins and this risk is dose- and time- dependent. Explanations for the conversion of a predisposed individual to diabetes are ambiguous including reductions in ubiquinone and adiponectin levels. However, the risk of new-onset diabetes mellitus is far outweighed by the statin-induced considerable decrease in cardiovascular events. Thus, prediabetic patients at high cardiovascular risk should not be denied high-dose statin therapy due to the small increase in the risk of developing diabetes since statins, especially at higher doses, cause greater reductions in cardiovascular events compared with standard statin doses. Moreover, lifestyle modification or even antidiabetic drugs are highly recommended in these individuals.
| S-EPMC4549696 | biostudies-literature