Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Community-Based Activity and Sedentary Patterns Are Associated With Cognitive Performance in Mobility-Limited Older Adults

Over the last few decades, considerable evidence shows that greater levels of aerobic exercise and cardiovascular fitness benefit cognitive performance. However, the degree to which free-living activity in community settings is related to cognitive performance remains unclear, particularly in older adults vulnerable to disability. Also, it is unknown whether the manner in which daily physical activity (PA) and sedentary time are accumulated throughout the day is associated with cognition. Cross-sectional associations between accelerometer-characterized PA and sedentary patterns and cognitive performance were examined in 1,274 mobility-limited older adults. Percent time spent in various bout lengths of PA (≥1, ≥2, and ≥5 min) and sedentary (≥1, ≥30, and ≥60 min) was defined as the number of minutes registered divided by total wear time × 100. Percent time was then tertiled for each bout length. Multiple linear regression models were used to estimate the associations between accelerometer bout variables and separate cognitive domains that included processing speed (Digit Symbol Coding; DSC), immediate and delayed recall (Hopkins Verbal Learning Test; HVLT), information processing and selective attention (Flanker), working memory (n-back), reaction time (switch and non-switch reaction time), and a composite score that averaged results from all cognitive tests. After adjusting for demographics, behavioral factors, and morbid conditions, more time spent in PA was associated with higher DSC for all bout lengths (p < 0.03 for all). Higher PA was associated with higher HVLT and global cognition scores but only for longer bout lengths (p < 0.05 for all). The association was largely driven by participants who spent the lowest amount of time performing activity while awake (p < 0.04). An inverse linear relationship was observed between total sedentary time and DSC (p = 0.02), but not for other measures of cognition. These results suggest that, while higher PA was associated with higher cognitive performance, PA’s association with memory was sensitive to bout duration. The time, but not the manner, spent in sedentary behaviors showed a minor association with executive function. Further research is warranted to characterize longitudinal changes in daily activity and sedentary patterns as potential biophysical markers of cognitive status in older adults

Designing clinical trials for assessing the effects of cognitive training and physical activity interventions on cognitive outcomes: The Seniors Health and Activity Research Program Pilot (SHARP-P) Study, a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The efficacy of non-pharmacological intervention approaches such as physical activity, strength, and cognitive training for improving brain health has not been established. Before definitive trials are mounted, important design questions on participation/adherence, training and interventions effects must be answered to more fully inform a full-scale trial.</p> <p>Methods</p> <p>SHARP-P was a single-blinded randomized controlled pilot trial of a 4-month physical activity training intervention (PA) and/or cognitive training intervention (CT) in a 2 × 2 factorial design with a health education control condition in 73 community-dwelling persons, aged 70-85 years, who were at risk for cognitive decline but did not have mild cognitive impairment.</p> <p>Results</p> <p>Intervention attendance rates were higher in the CT and PACT groups: CT: 96%, PA: 76%, PACT: 90% (p=0.004), the interventions produced marked changes in cognitive and physical performance measures (p≤0.05), and retention rates exceeded 90%. There were no statistically significant differences in 4-month changes in composite scores of cognitive, executive, and episodic memory function among arms. Four-month improvements in the composite measure increased with age among participants assigned to physical activity training but decreased with age for other participants (intervention*age interaction p = 0.01). Depending on the choice of outcome, two-armed full-scale trials may require fewer than 1,000 participants (continuous outcome) or 2,000 participants (categorical outcome).</p> <p>Conclusions</p> <p>Good levels of participation, adherence, and retention appear to be achievable for participants through age 85 years. Care should be taken to ensure that an attention control condition does not attenuate intervention effects. Depending on the choice of outcome measures, the necessary sample sizes to conduct four-year trials appear to be feasible.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00688155">NCT00688155</a></p

Physical activity and quality of life in community dwelling older adults

<p>Abstract</p> <p>Background</p> <p>Physical activity has been consistently associated with enhanced quality of life (QOL) in older adults. However, the nature of this relationship is not fully understood. In this study of community dwelling older adults, we examined the proposition that physical activity influences global QOL through self-efficacy and health-status.</p> <p>Methods</p> <p>Participants (N = 321, <it>M </it>age = 63.8) completed measures of physical activity, self-efficacy, global QOL, physical self worth, and disability limitations. Data were analyzed using covariance modeling to test the fit of the hypothesized model.</p> <p>Results</p> <p>Analyses indicated direct effects of a latent physical activity variable on self-efficacy but not disability limitations or physical self-worth; direct effects of self-efficacy on disability limitations and physical self worth but not QOL; and direct effects of disability limitations and physical self-worth on QOL.</p> <p>Conclusion</p> <p>Our findings support the role of self-efficacy in the relationship between physical activity and QOL as well as an expanded QOL model including both health status indicators and global QOL. These findings further suggest future PA promotion programs should include strategies to enhance self-efficacy, a modifiable factor for improving QOL in this population.</p

Power training and postmenopausal hormone therapy affect transcriptional control of specific co-regulated gene clusters in skeletal muscle

At the moment, there is no clear molecular explanation for the steeper decline in muscle performance after menopause or the mechanisms of counteractive treatments. The goal of this genome-wide study was to identify the genes and gene clusters through which power training (PT) comprising jumping activities or estrogen containing hormone replacement therapy (HRT) may affect skeletal muscle properties after menopause. We used musculus vastus lateralis samples from early stage postmenopausal (50–57 years old) women participating in a yearlong randomized double-blind placebo-controlled trial with PT and HRT interventions. Using microarray platform with over 24,000 probes, we identified 665 differentially expressed genes. The hierarchical clustering method was used to assort the genes. Additionally, enrichment analysis of gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was carried out to clarify whether assorted gene clusters are enriched with particular functional categories. The analysis revealed transcriptional regulation of 49 GO/KEGG categories. PT upregulated transcription in “response to contraction”—category revealing novel candidate genes for contraction-related regulation of muscle function while HRT upregulated gene expression related to functionality of mitochondria. Moreover, several functional categories tightly related to muscle energy metabolism, development, and function were affected regardless of the treatment. Our results emphasize that during the early stages of the postmenopause, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle power and potentially reducing the risk for aging-related muscle weakness. More specifically, PT and HRT may function through improving energy metabolism, response to contraction as well as by preserving functionality of the mitochondria

Identification of Y-Box Binding Protein 1 As a Core Regulator of MEK/ERK Pathway-Dependent Gene Signatures in Colorectal Cancer Cells

Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. Numerous candidate genes involved in disease and in factors of predictive, as well as of prognostic, value have been deduced from such molecular portraits, e.g. in cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. To identify regulators of transcriptome alterations, we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase pathway, computational prediction of regulatory elements in promoters of co-regulated genes, chromatin-based and functional cellular assays. We identified commonly co-regulated, proliferation-associated target genes that respond to the MAPK pathway. We recognized E2F and NFY transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of Y-box binding protein 1 (YBX1) by reporter gene, gel shift, and chromatin immunoprecipitation assays. We also validated the MAPK-dependent gene signature in colorectal cancers and provided evidence for the association of YBX1 with poor prognosis in colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated target genes are involved in executing malignant properties

The effect of regular walks on various health aspects in older people with dementia: protocol of a randomized-controlled trial

<p>Abstract</p> <p>Background</p> <p>Physical activity has proven to be beneficial for physical functioning, cognition, depression, anxiety, rest-activity rhythm, quality of life (QoL), activities of daily living (ADL) and pain in older people. The aim of this study is to investigate the effect of walking regularly on physical functioning, the progressive cognitive decline, level of depression, anxiety, rest-activity rhythm, QoL, ADL and pain in older people with dementia.</p> <p>Methods/design</p> <p>This study is a longitudinal randomized controlled, single blind study. Ambulatory older people with dementia, who are regular visitors of daily care or living in a home for the elderly or nursing home in the Netherlands, will be randomly allocated to the experimental or control condition. Participants of the experimental group make supervised walks of 30 minutes a day, 5 days a week, as part of their daily nursing care. Participants of the control group will come together three times a week for tea or other sedentary activities to control for possible positive effects of social interaction. All dependent variables will be assessed at baseline and after 6 weeks, and 3, 6, 9, 12 and 18 months of intervention.</p> <p>The dependent variables include neuropsychological tests to assess cognition, physical tests to determine physical functioning, questionnaires to assess ADL, QoL, level of depression and anxiety, actigraphy to assess rest-activity rhythm and pain scales to determine pain levels. Potential moderating variables at baseline are: socio-demographic characteristics, body mass index, subtype of dementia, apolipoprotein E (ApoE) genotype, medication use and comorbidities.</p> <p>Discussion</p> <p>This study evaluates the effect of regular walking as a treatment for older people with dementia. The strength of this study is that 1) it has a longitudinal design with multiple repeated measurements, 2) we assess many different health aspects, 3) the intervention is not performed by research staff, but by nursing staff which enables it to become a routine in usual care. Possible limitations of the study are that 1) only active minded institutions are willing to participate creating a selection bias, 2) the drop-out rate will be high in this population, 3) not all participants will be able to perform/understand all tests.</p> <p>Trial registration</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1482">NTR1482</a></p

Cardiometabolic Risk Factor Changes Observed in Diabetes Prevention Programs in US Settings: A Systematic Review and Meta-analysis

Background: The Diabetes Prevention Program (DPP) study showed that weight loss in high-risk adults lowered diabetes incidence and cardiovascular disease risk. No prior analyses have aggregated weight and cardiometabolic risk factor changes observed in studies implementing DPP interventions in nonresearch settings in the United States. Methods and Findings: In this systematic review and meta-analysis, we pooled data from studies in the United States implementing DPP lifestyle modification programs (focused on modest [5%–7%] weight loss through ≥150 min of moderate physical activity per week and restriction of fat intake) in clinical, community, and online settings. We reported aggregated pre- and post-intervention weight and cardiometabolic risk factor changes (fasting blood glucose [FBG], glycosylated hemoglobin [HbA1c], systolic or diastolic blood pressure [SBP/DBP], total [TC] or HDL-cholesterol). We searched the MEDLINE, EMBASE, Cochrane Library, and Clinicaltrials.gov databases from January 1, 2003, to May 1, 2016. Two reviewers independently evaluated article eligibility and extracted data on study designs, populations enrolled, intervention program characteristics (duration, number of core and maintenance sessions), and outcomes. We used a random effects model to calculate summary estimates for each outcome and associated 95% confidence intervals (CI). To examine sources of heterogeneity, results were stratified according to the presence of maintenance sessions, risk level of participants (prediabetes or other), and intervention delivery personnel (lay or professional). Forty-four studies that enrolled 8,995 participants met eligibility criteria. Participants had an average age of 50.8 years and body mass index (BMI) of 34.8 kg/m2, and 25.2% were male. On average, study follow-up was 9.3 mo (median 12.0) with a range of 1.5 to 36 months; programs offered a mean of 12.6 sessions, with mean participant attendance of 11.0 core sessions. Sixty percent of programs offered some form of post-core maintenance (either email or in person). Mean absolute changes observed were: weight -3.77 kg (95% CI: -4.55; -2.99), HbA1c -0.21% (-0.29; -0.13), FBG -2.40 mg/dL (-3.59; -1.21), SBP -4.29 mmHg (-5.73, -2.84), DBP -2.56 mmHg (-3.40, 1.71), HDL +0.85 mg/dL (-0.10, 1.60), and TC -5.34 mg/dL (-9.72, -0.97). Programs with a maintenance component achieved greater reductions in weight (additional -1.66kg) and FBG (additional -3.14 mg/dl). Findings are subject to incomplete reporting and heterogeneity of studies included, and confounding because most included studies used pre-post study designs. Conclusions: DPP lifestyle modification programs achieved clinically meaningful weight and cardiometabolic health improvements. Together, these data suggest that additional value is gained from these programs, reinforcing that they are likely very cost-effective