GAIT SLOWING AMONG FRAIL OLDER ADULTS: IS HIGHER DOPAMINERGIC SIGNALING PROTECTIVE?
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ABSTRACT:
SUBMITTER: Rosano C
PROVIDER: S-EPMC6845954 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:With age, performance of motor tasks becomes more reliant on cognitive resources to compensate for the structural and functional declines in the motor control regions in the brain. We hypothesized that participants with amnestic mild cognitive impairment (aMCI) are more prone to motor dysfunctions than cognitively normal older adults under dual-task conditions where competitive demands challenge cognitive functions while performing a motor task simultaneously. METHODS:Sixteen aMCI participants (females=9, age=64±5yrs, clinical dementia rating score=0.5) and 10 age- and education-matched cognitively normal adults (females=5, age=62±6yrs) participated. Using a 10-meter-walk test (10MW), gait velocity was recorded at baseline and under 4 different dual-task (DT) conditions designed to challenge working memory, executive function, and episodic memory. Specifically, DT1: verbal fluency; DT2: 5-digit backward span; DT3: serial-7 subtraction; and DT4: 3-item delayed recall. Physical function was measured by Timed Up-and-Go (TUG), simple reaction time (RT) to a free-falling yardstick, and functional reach (FR). RESULTS:No difference was found in physical functions, aerobic fitness, and exercise cardiopulmonary responses between aMCI participants and controls. However, aMCI participants showed more pronounced gait slowing from baseline when compared to the controls (p<0.05; p=0.001; p<0.001; p<0.001, respectively). CONCLUSIONS:Our finding supports the theory of shared resource of motor and cognitive control. Participants with aMCI manifested more gait slowing than cognitively-normal older adults under DT conditions, with the largest differences during tests of working and episodic memory. The outcome of dual-task assessment shows promise as a potential marker for detection of aMCI and early Alzheimer disease.
| S-EPMC4082490 | biostudies-literature
Project description:OBJECTIVES:To examine whether the association between hypertension and decline in gait speed is significant in well-functioning older adults and whether other health-related factors, such as brain, kidney, and heart function, can explain it. DESIGN:Longitudinal cohort study. SETTING:Cardiovascular Health Study. PARTICIPANTS:Of 2,733 potential participants with a brain magnetic resonance imaging (MRI) scan, measures of mobility and systolic blood pressure (BP), no self-reported disability in 1992 to 1994 (baseline), and with at least 1 follow-up gait speed measurement through 1997 to 1999, 643 (aged 73.6, 57% female, 15% black) who had received a second MRI in 1997 to 1999 and an additional gait speed measure in 2005 to 2006 were included. MEASUREMENTS:Mixed models with random slopes and intercepts were adjusted for age, race, and sex. Main explanatory factors included white matter hyperintensity progression, baseline cystatin-C, and left cardiac ventricular mass. Incidence of stroke and dementia, BP trajectories, and intake of antihypertensive medications during follow-up were tested as other potential explanatory factors. RESULTS:Higher systolic BP was associated with faster rate of gait speed decline in this selected group of 643 participants, and results were similar in the parent cohort (N = 2,733). Participants with high BP (n = 293) had a significantly faster rate of gait speed decline than those with baseline BP less than 140/90 mmHg and no history of hypertension (n = 350). Rates were similar for those with history of hypertension who were uncontrolled (n = 110) or controlled (n = 87) at baseline and for those who were newly diagnosed (n = 96) at baseline. Adjustment for explanatory factors or for other covariates (education, prevalent cardiovascular disease, physical activity, vision, mood, cognition, muscle strength, body mass index, osteoporosis) did not change the results. CONCLUSION:High BP accelerates gait slowing in well-functioning older adults over a long period of time, even for those who control their BP or develop hypertension later in life. Health-related measurements did not explain these associations. Future studies to investigate the mechanisms linking hypertension to slowing gait in older adults are warranted.
| S-EPMC3637929 | biostudies-literature
Project description:IntroductionPhysical activity (PA) is important for healthy ageing. Better insight into objectively measured PA levels in older adults is needed, since most previous studies employed self-report measures for PA assessment, which are associated with overestimation of PA.AimThis study aimed to provide insight in objectively measured indoor and outdoor PA of older adults, and in PA differences by frailty levels.MethodsData were collected among non-frail (N = 74) and frail (N = 10) subjects, aged 65 to 89 years. PA, measured for seven days with accelerometers and GPS-devices, was categorized into three levels of intensity (sedentary, light, and moderate-to-vigorous PA).ResultsOlder adults spent most time in sedentary and light PA. Subjects spent 84.7%, 15.1% and 0.2% per day in sedentary, light and moderate-to-vigorous PA respectively. On average, older adults spent 9.8 (SD 23.7) minutes per week in moderate-to-vigorous activity, and 747.0 (SD 389.6) minutes per week in light activity. None of the subjects met the WHO recommendations of 150 weekly minutes of moderate-to-vigorous PA. Age-, sex- and health status-adjusted results revealed no differences in PA between non-frail and frail older adults. Subjects spent significantly more sedentary time at home, than not at home. Non-frail subjects spent significantly more time not at home during moderate-to-vigorous activities, than at home.ConclusionsObjective assessment of PA in older adults revealed that most PA was of light intensity, and time spent in moderate-to-vigorous PA was very low. None of the older adults met the World Health Organization recommendations for PA. These levels of MVPA are much lower than generally reported based on self-reported PA. Future studies should employ objective methods, and age specific thresholds for healthy PA levels in older adults are needed. These results emphasize the need for effective strategies for healthy PA levels for the growing proportion of older adults.
| S-EPMC4409218 | biostudies-literature
Project description:Vitamin D deficiency is common among older adults and has been linked to muscle weakness. Vitamin D supplementation has been proposed as a strategy to improve muscle function in older adults. The aim of this study was to investigate the effect of calcifediol (25-hydroxycholecalciferol) on whole genome gene expression in skeletal muscle of vitamin D deficient frail older adults. A double-blind placebo controlled trial was conducted in vitamin D deficient frail older adults (aged above 65), characterized by blood 25-hydroxycholecalciferol concentrations between 20 and 50 nmol/L. Subjects were randomized across the placebo group (n=12) and the calcifediol group (n=10, 10 µg per day). Muscle biopsies were obtained before and after six months of calcifediol or placebo supplementation and subjected to whole genome gene expression profiling using Affymetrix HuGene 2.1ST arrays. Expression of the vitamin D receptor gene was virtually undetectable in human skeletal muscle biopsies. Calcifediol supplementation led to a significant increase in blood 25-hydroxycholecalciferol levels compared to the placebo group. No difference between treatment groups was observed on strength outcomes. The whole transcriptome effects of calcifediol and placebo were very weak. Correcting for multiple testing using false discovery rate did not yield any differentially expressed genes using any sensible cut-offs. P-values were uniformly distributed across all genes, suggesting that low p-values are likely to be false positives. Partial least squares-discriminant analysis and principle component analysis was unable to separate treatment groups. Calcifediol supplementation did not affect the skeletal muscle transcriptome in frail older adults. Our findings indicate that vitamin D supplementation has no effects on skeletal muscle gene expression, suggesting that skeletal muscle may not be a direct target of vitamin D in older adults.
2019-06-10 | GSE123993 | GEO
Project description:BACKGROUND:As the number of older adults increases, so does the number of frail older adults. Although anthropometry has been widely used as a way to stratify the overall mortality risk of a person, the significance of these measurements becomes blurred in the case of frail older adults who have changes in body composition. Therefore, the aim of this study is to determine the association of anthropometric measurements (body mass index, knee-adjusted height body mass index, waist-to-hip ratio and calf circumference) with mortality risk in a group of older Mexican adults. METHODS:This is a longitudinal analysis of the Mexican Health and Aging sub-sample (with biomarkers, n?=?2573) from the first wave in 2001, followed-up to the last available wave in 2015. Only frail 50-year or older adults (Frailty Index with a cut-off value of 0.21 or higher, was used) were considered for this analysis (n?=?1298). A survival analysis was performed with Kaplan-Meier curves and Cox regression models (unadjusted and adjusted for confounding). Socio-demographic, health risks, physical activity and comorbidities were variables used for adjusting the multivariate models. RESULTS:From the total sample of 1298 older adults, 32.5% (n?=?422) died during follow-up. The highest hazard ratio in the adjusted model was for calf circumference 1.31 (95% confidence interval 1.02-1.69, p?=?0.034). Other measurements were not significant. CONCLUSIONS:Anthropometric measurements have different significance in frail older adults, and these differences could have implications on adverse outcomes. Calf circumference has a potential value in predicting negative health outcomes.
| S-EPMC6109418 | biostudies-literature
Project description:Frailty is associated with gait variability in several quantitative parameters, including high stride time variability. However, the associations between joint kinematics during walking and increased gait variability with frailty remain unclear. In the current study, principal component analysis was used to identify the key joint kinematics characteristics of gait related to frailty. We analyzed whole kinematic waveforms during the entire gait cycle obtained from the pelvis and lower limb joint angle in 30 older women (frail/prefrail: 15 participants; non-frail: 15 participants). Principal component analysis was conducted using a 60 × 1224 input matrix constructed from participants' time-normalized pelvic and lower-limb-joint angles along three axes (each leg of 30 participants, 51 time points, four angles, three axes, and two variables). Statistical analyses revealed that only principal component vectors 6 and 9 were related to frailty. Recombining the joint kinematics corresponding to these principal component vectors revealed that frail older women tended to exhibit greater variability of knee- and ankle-joint angles in the sagittal plane while walking compared with non-frail older women. We concluded that greater variability of knee- and ankle-joint angles in the sagittal plane are joint kinematic characteristics of gait related to frailty.
| S-EPMC8803892 | biostudies-literature
Project description:Sarcopenia, a core feature of the physical frailty syndrome, is characterized by multisystem physiological dysregulation. No study has explored qualitatively the hierarchical network of relationships among different dysregulated pathways involved in the pathogenesis of sarcopenia. We used 40 blood biomarkers belonging to community-dwelling prefrail and frail older persons to derive measures of multiple physiological pathways, and structural equation modeling to generate path network models of the multisystem physiological dysregulations associated with muscle mass and function (MMF). Insulin-leptin signaling and energy regulation, anabolic sex steroid regulation (testosterone, leptin), and tissue oxygenation (hemoglobin, red cell count) appear to be primary mediating factors exerting direct influences on MMF. There was additionally secondary mediatory involvement of myocyte- and adipocyte-derived cytokines, hypothalamic pituitary adrenal (HPA) stress hormones (cortisol, DHEAS), glomerular function, and immune cell regulatory and inflammatory cytokines and glycoproteins. We conclude that within a hierarchical network of multisystem physiological dysregulations in sarcopenia, dysregulated anabolic and catabolic pathways via sex steroids and insulin-leptin dual signaling and tissue hypoxemia are primary physiological dysregulations responsible for sarcopenia and frailty.
| S-EPMC6260914 | biostudies-literature
Project description:Background: Frailty, a state of increased vulnerability, could play a role in the progression of vascular dementia. We aim to describe the changes in cerebrovascular reactivity of older adults with frailty and vascular-type mild cognitive impairment (MCIv). Methods: This was a cross-sectional study. A comprehensive geriatric assessment, neuropsychological evaluation, and transcranial Doppler ultrasound (TCD) was performed on 180 participants who were allocated into four groups: healthy (n = 74), frail (n = 40), MCIv (n = 35), and mixed (frail + MCIv) (n = 31). ANOVA and Kruskal-Wallis tests were used for the analysis of continuous variables with and without normal distribution. Multinomial logistic regression was constructed to identify associated covariates. Results: Subjects in the mixed group, compared to healthy group, were older (75.0 ± 5.9 vs 70.3 ± 5.9 years; p < 0.001), showed lower education (9.3 ± 6.4 vs 12.2 ± 4.0 years; p = 0.054), greater frequency of diabetes (42% vs 12%; p = 0.005), worse cognitive performance (z = -0.81 ± 0.94), and reduced left medial-cerebral artery cerebrovascular reactivity (0.43 ± 0.42 cm/s). The mixed group was associated with age (odds ratio (OR) 1.16, 95% Confidence Interval (CI) = 1.06-1.27; p < 0.001), diabetes (OR 6.28, 1.81-21.84; p = 0.004), and Geriatric Depression Scale (GDS) score (OR 1.34, 95% CI = 1.09-1.67; p = 0.007). Conclusions: Frailty among older adults was associated with worse cognitive performance, diabetes, and decreased cerebral blood flow.
| S-EPMC6770260 | biostudies-other
Project description:BACKGROUND:Bisphosphonates are seldom used in frail, older adults, in part due to lack of direct evidence of efficacy in this population and increasing concerns about safety. OBJECTIVE:We estimated the effects of bisphosphonates on hip fractures, nonvertebral fractures, and severe esophagitis among frail, older adults. DESIGN:Population-based retrospective cohort using 2008 to 2013 linked national Minimum Data Set assessments; Online Survey Certification and Reporting System records; and Medicare claims. SETTING:US nursing homes (NHs). PARTICIPANTS:Long-stay NH residents 65 years and older without recent osteoporosis medication use (N = 24,571). Bisphosphonate initiators were 1:1 propensity score matched to calcitonin initiators (active comparator). MEASUREMENTS:Hospitalized hip fracture, nonvertebral fracture, and esophagitis outcomes were measured using part A claims. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated, controlling for over 100 baseline characteristics. RESULTS:The matched cohort included 5209 new bisphosphonate users and an equal number of calcitonin users (mean age [SD] = 85 [8] years; 87% female; 52% moderate-severe cognitive impairment). Over a mean follow-up of 2.5 (SD = 1.7) years, 568 residents (5.5%) had a hip fracture, 874 (8.4%) had a nonvertebral fracture, and 199 (1.9%) had a hospitalized esophagitis event. Users of bisphosphonates were less likely than calcitonin users to experience hip fracture (HR = 0.83; 95% CI = 0.71-0.98), with an average gain in time without fracture of 28.4 days (95% CI = 6.0-50.8 days). Bisphosphonate and calcitonin users had similar rates of nonvertebral fracture (HR = 0.91; 95% CI = 0.80-1.03) and esophagitis events (HR = 1.11; 95% CI = 0.84-1.47). The effects of bisphosphonates on fractures and esophagitis were generally homogeneous across subgroups, including those defined by age, sex, history of prior fracture, and baseline fracture risk. CONCLUSIONS:Use of bisphosphonates is associated with a meaningful reduction in hip fracture among frail, older adults, but little difference in nonvertebral fracture or severe esophagitis. J Am Geriatr Soc 67:768-776, 2019.
| S-EPMC6705123 | biostudies-literature
Project description:The present study was undertaken to evaluate serum levels of pro-inflammatory cytokines in Tunisian older adults and to examine the relationships between inflammatory marker levels, geriatric, and biochemical parameters. A cross-sectional study was conducted in a population of Tunisian older adults (N = 141, aged 65 and over). Patients were recruited from the Department of Internal Medicine, Fattouma Bourguiba University Hospital (Monastir, Tunisia) and from a nursing home (Sousse, Tunisia). Comprehensive geriatric assessment, history taking and examination including functional and nutritional assessment were done for each participant. Enzyme-linked immunosorbent assay (ELISA) test was used to measure serum cytokine (TNF-α, IL-8, IL-6) levels. The modified Short Emergency Geriatric Assessment score (SEGAm) were used to classify patients as 51 very-frail, 40 frail, and 50 non-frail. The age of the participants (80 men, 61 women) ranged from 65 to 97 years. Serum levels of TNF-α, IL-8 and C-reactive protein (CRP) were significantly higher in very-frail participants compared to frail and non-frail ones. However, no significant differences in IL-6 levels were detected among frailty groups. After adjustment for age, CRP and IL-8 levels remained significantly associated with frailty. Analysis of the receiver operating characteristic (ROC) curve corresponding to IL-8 showed an area under the curve of 0.7 (p = 0.003; 95% CI [0.58-0.81]) and a predictive threshold of 5.27 pg/ml. Positive correlations were found between frailty score, IL-6, and IL-8 levels. In addition, a significant positive correlation was observed between IL-8 levels and Timed Up and Go test results. However, a negative correlation was observed between Mini Nutritional Assessment Short-Form score, IL-6 and CRP levels, as well as between Activities of Daily Living score and serum levels of TNF-α, IL-6, and CRP. In conclusion, the key findings of this study collectively support a role of pro-inflammatory cytokines, TNF-α, CRP, and especially IL-8 in the development of frailty in older adults.
| S-EPMC7652286 | biostudies-literature