A multimodality intervention to improve musculoskeletal health, function, metabolism, and well-being in spinal cord injury: study protocol for the FIT-SCI randomized controlled trial.

BACKGROUND: A spinal cord injury (SCI) is a devastating, life-changing event that has profoundly deleterious effects on an individual's health and well-being. Dysregulation of neuromuscular, cardiometabolic, and endocrine organ systems following an SCI contribute to excess morbidity, mortality and a poor quality of life. As no effective treatments currently exist for SCI, the development of novel strategies to improve the functional and health status of individuals living with SCI are much needed. To address this knowledge gap, the current study will determine whether a Home-Based Multimodality Functional Recovery and Metabolic Health Enhancement Program that consists of functional electrical stimulation of the lower extremity during leg cycling (FES-LC) plus arm ergometry (AE) administered using behavioral motivational strategies, and testosterone therapy, is more efficacious than FES-LC plus AE and placebo in improving aerobic capacity, musculoskeletal health, function, metabolism, and wellbeing in SCI. METHODS: This single-site, randomized, placebo-controlled, parallel group trial will enroll 88 community-dwelling men and women, 19 to 70 years of age, with cervical and thoracic level of SCI, ASIA Impairment Scale grade: A, B, C, or D, 6 months or later after an SCI. Participants randomized to the multimodality intervention will undergo 16 weeks of home-based FES-LC and AE training plus testosterone undecanoate. Testosterone undecanoate injections will be administered by study staff in clinic or by a visiting nurse in the participant's home. The control group will receive 16 weeks of home-based FES-LC and AE exercise plus placebo injections. The primary outcome of this trial is peak aerobic capacity, measured during an incremental exercise testing protocol. Secondary outcomes include whole body and regional lean and adipose tissue mass; muscle strength and power; insulin sensitivity, lipids, and inflammatory markers; SCI functional index and wellbeing (mood, anxiety, pain, life satisfaction and depressive symptoms); and safety. DISCUSSION: We anticipate that a multimodality intervention that simultaneously addresses multiple physiological impairments in SCI will result in increased aerobic capacity and greater improvements in other musculoskeletal, metabolic, functional and patient-reported outcomes compared to the control intervention. The findings of this study will have important implications for improving the care of people living with an SCI. TRIAL REGISTRATION: ClinicalTrials.gov :  ( NCT03576001 ). Prospectively registered: July 3, 2018.

Cognitive Motor Dual Task Costs in Older Adults with Motoric Cognitive Risk Syndrome.

The purpose of this study was to characterize Cognitive Motor Dual Task (CMDT) costs for a community-based sample of older adults with Motoric Cognitive Risk Syndrome (MCR), as well as investigate associations between CMDT costs and cognitive performance. Twenty-five community-dwelling older adults (ages 60-89 years) with MCR performed single and dual task complex walking scenarios, as well as a computerized cognitive testing battery. Participants with lower CMDT costs had higher scores on composite measures of Working Memory, Processing Speed, and Shifting, as well as an overall cognitive composite measure. In addition, participants with faster single task gait velocity had higher scores on composite measures of Working Memory, Processing Speed, and overall cognition. Taken together, these results suggest that CMDT paradigms can help to elucidate the interplay between cognitive and motor abilities for older adults with MCR.

URBAN-RURAL DIFFERENCES IN THE PREVALENCE OF MUSCLE WEAKNESS AND SLOW GAIT SPEED: A CROSS-SECTIONAL ANALYSIS FROM THE NHANES (2001-2002 AND 2011-2014).

Background: Older adults living in rural areas suffer from health inequities compared to their urban counterparts. These include comorbidity burden, poor diet, and physical inactivity, which are also risk factors for sarcopenia, for which muscle weakness and slow gait speed are domains. To date, no study has examined urban-rural differences in the prevalence of muscle weakness and slow gait speed in older adults living in the United States. Objective: To compare the prevalence of grip strength weakness and slow gait speed between urban and rural older adults living in the United States. Design: A cross-sectional, secondary data analysis of two cohorts from the National Health and Nutrition Examination Survey (NHANES), using gait speed or grip strength data, and urban-rural residency, dietary, examination, questionnaire and demographic data. Participants: 2,923 adults (≥ 60 yrs.). Measures: Grip weakness was defined as either, an absolute grip strength of <35 kg. and <20 kg. or grip strength divided by body mass index (GripBMI) of <1.05 and <0.79 for men and women, respectively. Slow gait speed was defined as a usual gait speed of ≤0.8m/s. Results: The prevalence of GripBMI weakness was significantly higher in urban compared to rural participants (27.4% vs. 19.2%; p=0.001), whereas their absolute grip strength was lower (31.75(±0.45) vs. 33.73(±0.48)). No urban-rural differences in gait speed were observed. Conclusions: Older adults residing in urban regions of the United States were weaker compared to their rural counterparts. This report is the first to describe urban-rural differences in handgrip strength and slow gait speed in older adults living in the United States.

Circulating Interleukin-6 Is Associated with Skeletal Muscle Strength, Quality, and Functional Adaptation with Exercise Training in Mobility-Limited Older Adults.

BACKGROUND: Human aging is characterized by a chronic, low-grade inflammation suspected to contribute to reductions in skeletal muscle size, strength, and function. Inflammatory cytokines, such as interleukin-6 (IL-6), may play a role in the reduced skeletal muscle adaptive response seen in older individuals. OBJECTIVES: To investigate relationships between circulating IL-6, skeletal muscle health and exercise adaptation in mobility-limited older adults. DESIGN: Randomized controlled trial. SETTING: Exercise laboratory on the Health Sciences campus of an urban university. PARTICIPANTS: 99 mobility-limited (Short Physical Performance Battery (SPPB) ≤9) older adults. INTERVENTION: 6-month structured physical activity with or without a protein and vitamin D nutritional supplement. MEASUREMENTS: Circulating IL-6, skeletal muscle size, composition (percent normal density muscle tissue), strength, power, and specific force (strength/CSA) as well as physical function (gait speed, stair climb time, SPPB-score) were measured pre- and post-intervention. RESULTS: At baseline, Spearman's correlations demonstrated an inverse relationship (P<0.05) between circulating IL-6 and thigh muscle composition (r = -0.201), strength (r = -0.311), power (r = -0.210), and specific force (r = -0.248), and positive association between IL-6 and stair climb time (r = 0.256; P<0.05). Although the training program did not affect circulating IL-6 levels (P=0.69), reductions in IL-6 were associated with gait speed improvements (r = -0.487; P<0.05) in "higher" IL-6 individuals (>1.36 pg/ml). Moreover, baseline IL-6 was inversely associated (P<0.05) with gains in appendicular lean mass and improvements in SPPB score (r = -0.211 and -0.237, respectively). CONCLUSIONS: These findings implicate age-related increases in circulating IL-6 as an important contributor to declines in skeletal muscle strength, quality, function, and training-mediated adaptation. Given the pervasive nature of inflammation among older adults, novel therapeutic strategies to reduce IL-6 as a means of preserving skeletal muscle health are enticing.

NUTRITIONAL RISK STATUS, DIETARY INTAKE AND COGNITIVE PERFORMANCE IN OLDER ADULTS WITH MOTORIC COGNITIVE RISK SYNDROME.

Background: Modifiable lifestyle factors such as diet are associated with cognitive decline and dementia. Greater understanding of the nutritional intake of older adults who are at increased risk for cognitive decline may allow for the development of more effective dietary interventions to prevent or delay the onset of dementia. Objectives: The purpose of this study was to characterize the nutritional status, diet quality and individual nutritional components of older adults with motoric cognitive risk syndrome (MCR). MCR is a pre-dementia syndrome classified by slow gait speed and subjective memory impairments. Design: Cross-sectional analysis. Setting: A community-based senior center located in an urban setting. Participants: Twenty-five community-dwelling older adults with MCR aged 60-89 yrs. Measurements: Nutritional risk status was determined using the Nestle Mini Nutritional Assessment (MNA). A food frequency questionnaire was used to quantify: overall dietary quality using the Healthy Eating Index (HEI); adherence to the Mediterranean-DASH for Neurodegenerative Delay (MIND) dietary pattern; and intake of individual nutritional components shown to be protective or harmful for cognitive function in older adults. Participants completed a computerized cognitive testing battery to assess cognitive abilities. Results: More than one third (36%) of participants were at increased risk for malnutrition. Participants at lower risk for malnutrition had better working memory (r = 0.40, p = 0.04), executive functioning (r = 0.44, p = 0.03), and overall cognition (r = 0.44, p = 0.03). While participants generally consumed a reasonable quality diet (HEI = 65.15), 48% of participants had poor adherence to a neuroprotective MIND dietary pattern. Higher intake of B-complex vitamins was associated with better task switching (r = 0.40, p ≤ 0.05) and faster processing speeds (r = 0.39, p ≤ 0.05). Higher vitamin C intake was associated with better executive functioning (r = 0.40, p ≤ 0.05). Conclusions: Our findings suggest that a significant proportion of older adults with MCR may be at increased risk for malnutrition. While the diet quality of older adults with MCR appeared to need improvement, future studies should investigate the effects of more specific nutritional interventions, including the MIND diet, on cognition in at-risk older adults.

Lower-Extremity Torque Capacity and Physical Function in Mobility-Limited Older Adults.

OBJECTIVES: Skeletal muscle weakness and an increase in fatigability independently contribute to age-related functional decline. The objective of this study was to examine the combined contribution of these deficiencies (i.e., torque capacity) to physical function, and then to assess the functional implications of progressive resistance training (PRT) mediated-torque capacity improvements in mobility-limited older adults. DESIGN: Randomized controlled trial. SETTING: Exercise laboratory on the Health Sciences campus of an urban university. PARTICIPANTS: Seventy mobility-limited (Short Physical Performance Battery (SPPB) ≤9) older adults (~79 yrs). INTERVENTION: Progressive resistance training or home-based flexibility 3 days/week for 12 weeks. MEASUREMENTS: Torque capacity was defined as the sum of peak torques from an isokinetic knee extension fatigue test. Relationships between torque capacity and performance-based and patient-reported functional measures before and after PRT were examined using partial correlations adjusted for age, sex, and body mass index. RESULTS: Torque capacity explained (P<0.05) 10 and 28% of the variance in six-minute walk distance and stair climb time, respectively. PRT-mediated torque capacity improvements were paralleled by increases (P<0.05) in self-reported activity participation (+20%) and advanced lower extremity function (+7%), and associated (P<0.05) with a reduction in activity limitations (r=0.44) and an improved SPPB score (r=0.32). CONCLUSION: Skeletal muscle torque capacity, a composite of strength and fatigue, may be a proximal determinant of physical function in mobility-limited older individuals. To more closely replicate the musculoskeletal demands of real-life tasks, future studies are encouraged to consider the combined interaction of distinct skeletal muscle faculties to overall functional ability in older adults.

Cognitive Performance Does not Limit Physical Activity Participation in the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P).

OBJECTIVES: We examined whether multiple domains of baseline cognitive performance were associated with prospective physical activity (PA) adherence in the Lifestyle Interventions and Independence for Elders Pilot study (LIFE-P). DESIGN, SETTING, PARTICIPANTS: The LIFE-P study was a single-blind, multicenter, randomized controlled trial of a PA intervention compared to a successful aging educational intervention in sedentary, mobility-limited older adults. INTERVENTION: A 12-month structured, moderate-intensity, multi-modal PA program that included walking, resistance training, and flexibility exercises. For the first 2 months (adoption), 3 center-based exercise sessions (40-60 min) / week were conducted. During the next 4 months (transition), center-based sessions were conducted 2 times / week. The subsequent maintenance phase consisted of optional once-to-twice-per-week center-based sessions and home-based PA. MEASUREMENTS: Tests of executive and global cognitive functioning, working memory and psychomotor speed were administered at baseline. Median test scores were used to dichotomize participants into low or high cognitive performance groups. RESULTS: 52 mobility-limited older adults (age: 76.9 ±5 yrs) were randomized to the PA arm of LIFE-P. Compared to participants with high cognitive performance, participants with low performance had similar PA adherence rates (all P ≥ 0.34). Furthermore, weak and non-significant univariate relationships were elicited between all measures of cognition and overall PA adherence levels (r values ranged: -0.20 to 0.12, P ≥ 0.12). CONCLUSION: These data suggest that cognitive performance does not limit long-term PA adherence in mobility-limited older adults. Additional studies in larger cohorts are warranted to verify these findings.

Effect of Structured Physical Activity and Nutritional Supplementation on Physical Function in Mobility-Limited Older Adults: Results from the VIVE2 Randomized Trial.

OBJECTIVES: The interactions between nutritional supplementation and physical activity on changes in physical function among older adults remain unclear. The primary objective of this study was to examine the impact of nutritional supplementation plus structured physical activity on 400M walk capacity in mobility-limited older adults across two sites (Boston, USA and Stockholm, Sweden). DESIGN: All subjects participated in a physical activity program (3x/week for 24 weeks), involving walking, strength, balance, and flexibility exercises. Subjects were randomized to a daily nutritional supplement (150kcal, 20g whey protein, 800 IU vitamin D) or placebo (30kcal, non-nutritive). SETTING: Participants were recruited from urban communities at 2 field centers in Boston MA USA and Stockholm SWE. PARTICIPANTS: Mobility-limited (Short Physical Performance Battery (SPPB) ≤9) and vitamin D insufficient (serum 25(OH) D 9 - 24 ng/ml) older adults were recruited for this study. MEASUREMENTS: Primary outcome was gait speed assessed by the 400M walk. RESULTS: 149 subjects were randomized into the study (mean age=77.5±5.4; female=46.3%; mean SPPB= 7.9±1.2; mean 25(OH)D=18.7±6.4 ng/ml). Adherence across supplement and placebo groups was similar (86% and 88%, respectively), and was also similar across groups for the physical activity intervention (75% and 72%, respectively). Both groups demonstrated an improvement in gait speed with no significant difference between those who received the nutritional supplement compared to the placebo (0.071 and 0.108 m/s, respectively (p=0.06)). Similar effects in physical function were observed using the SPPB. Serum 25(OH)D increased in supplemented group compared to placebo 7.4 ng/ml versus 1.3 ng/ml respectively. CONCLUSION: Results suggest improved gait speed following physical activity program with no further improvement with added nutritional supplementation.

Accelerometer Assessment of Physical Activity and Its Association with Physical Function in Older Adults Residing at Assisted Care Facilities.

OBJECTIVES: To describe levels of physical activity among older adults residing at assisted care facilities and their association with physical function. DESIGN: Cross-sectional analysis. SETTING: Assisted care facilities within the greater Boston, MA area. PARTICIPANTS: Older adults aged 65 years and older (N = 65). MEASUREMENTS: Physical Activity Level (PAL) as defined by quartiles from accelerometry (counts and steps), Short Physical Performance Battery (SPPB) Score, gait speed, and handgrip strength. RESULTS: Participants in the most active accelerometry quartile engaged in 25 minutes/week of moderate to vigorous physical activity (MVPA) and walked 2,150 steps/day. These individuals had an SPPB score, 400 meter walk speed, and handgrip strength that was 3.7-3.9 points, 0.3-0.4 meters/second, and 4.5-5.1 kg greater respectively, than individuals in the lowest activity quartile, who engaged in less than 5 min/wk of MVPA or took fewer than 460 steps/day. CONCLUSION: Despite engaging in physical activity levels far below current recommendations (150 min/week of MVPA or > 7000 steps/day), the most active older adults in this study exhibited clinically significant differences in physical function relative to their less active peers. While the direction of causality cannot be determined from this cross-sectional study, these findings suggest a strong association between PAL and physical function among older adults residing in an assisted care facility.

Disseminating a Clinically Effective Physical Activity Program to Preserve Mobility in a Community Setting for Older Adults.

BACKGROUND: As the population of older adults continues to increase, the dissemination of strategies to maintain independence of older persons is of critical public health importance. Recent large-scale clinical trial evidence has definitively shown intervention of moderate-intensity physical activity (PA) reduces major mobility disability in at-risk older adults. However, it remains unknown whether structured PA interventions, with demonstrated efficacy in controlled, clinical environments, can be successfully disseminated into community settings to benefit wider populations of older adults. OBJECTIVE: To assess the dissemination of an evidence-based PA program for older adults by evaluating program participation and its impact on mobility, strength and quality of life. SETTING: An urban senior center. PARTICIPANTS: Fifty older adults (71.2 ± 8 years aged; BMI: 30.1 ± 7 kg/m2). INTERVENTION: Average of 8.0 ± 1.8 months of participation in the Fit-4-Life Program, a community-based PA and nutrition counseling intervention. MEASUREMENTS: Mobility (Short Physical Performance Battery (SPPB)), self-reported physical activity (CHAMPS questionnaire), leg strength, grip strength, and quality of life (Quality of Well-Being Self-Administered (QWB-SA) scale) were assessed at baseline and follow-up. RESULTS: Mean attendance was 55.8%. Fourteen participants were lost to follow-up. Those who dropped-out engaged in less PA at baseline (78 ± 108 mins/wk) compared to those who completed follow-up (203 ± 177 mins/wk, P=0.01). Participants exhibited sustained increases of PA (65 ± 153 mins/wk, P= 0.08), and there were meaningful improvements in SPPB (0.5 ± 0.2, P< 0.01), knee extensor strength (2.6 ± 4.4 kg, P< 0.01) and QWB-SA (0.04 ± 0.09, P= 0.05). CONCLUSION: The dissemination of a clinically efficacious PA intervention into a community-based setting can improve mobility, strength and quality of life for older adults. This knowledge may be helpful for the design and implementation of larger-scale PA intervention studies designed to preserve mobility in older adults within community-based settings.

Collaborative Evaluation of the Healthy Habits Program: An Effective Community Intervention to Improve Mobility and Cognition of Chinese Older Adults Living in the U.S.

OBJECTIVES: There is a growing demand to reduce ethnic health disparities. The Healthy Habits Program (HHP) was implemented to provide a community-based physical activity and education intervention for Chinese older adults living in Boston, Massachusetts. This study evaluated the HHP by assessing outcomes that are critical for maintaining independence of older persons. DESIGN, SETTING AND PARTICIPANTS: Quantitative evaluation was performed on 50 Chinese older adults enrolled in the HHP. The community members were trained in data collection and management. MEASUREMENTS: Cognition (Mini Mental State Examination (MMSE), Trail Making Test and Complex Walking Task), mobility (Short Physical Performance Battery (SPPB) and maximal gait speed), depressive symptoms (Patient Health Questionnaire-9), perceived disability (World Health Organization Disability Assessment 2.0), nutritional status (Mini Nutrition Assessment®), and strength (grip and leg strength) were assessed at baseline and at 6 months. All tests were translated into Chinese. RESULTS: Of the 50 participants (mean age 68.4 years; 68% female), 78% achieved the goal of performing exercise ≥3 times/week. After 6 months, clinically meaningful improvements were observed in mobility (mean SPPB score changed from 10.3 to 11.1 points; p=0.01) and cognition (mean MMSE score changed from 26.0 to 27.8 points; p=0.001). There were also statistically significant improvements in executive function, depressive symptoms and perceived disability (p<0.05). CONCLUSION: Culturally sensitive community interventions, such as the HHP, are effective for improving mobility and cognition of Chinese older adults. This reveals the potential of promoting successful aging in minority populations through community settings, and should be advocated to reduce ethnic health disparities in the U.S.

Age-associated declines in muscle mass, strength, power, and physical performance: impact on fear of falling and quality of life.

UNLABELLED: This 3-year longitudinal study among older adults showed that declining muscle mass, strength, power, and physical performance are independent contributing factors to increased fear of falling, while declines of muscle mass and physical performance contribute to deterioration of quality of life. Our findings reinforce the importance of preserving muscle health with advancing age. INTRODUCTION: The age-associated loss of skeletal muscle quantity and function are critical determinants of independent physical functioning in later life. Longitudinal studies investigating how decrements in muscle components of sarcopenia impact fear of falling (FoF) and quality of life (QoL) in older adults are lacking. METHODS: Twenty-six healthy older subjects (age, 74.1 ± 3.7; Short Physical Performance Battery (SPPB) score ≥10) and 22 mobility-limited older subjects (age, 77.2 ± 4.4; SPPB score ≤9) underwent evaluations of lower extremity muscle size and composition by computed tomography, strength and power, and physical performance at baseline and after 3-year follow-up. The Falls Efficacy Scale (FES) and Short Form-36 questionnaire (SF-36) were also administered at both timepoints to assess FoF and QoL, respectively. RESULTS: At 3-year follow-up, muscle cross-sectional area (CSA) (p < 0.013) and power decreased (p < 0.001), while intermuscular fat infiltration increased (p < 0.001). These decrements were accompanied with a longer time to complete 400 m by 22 ± 46 s (p < 0.002). Using linear mixed-effects regression models, declines of muscle CSA, strength and power, and SPPB score were associated with increased FES score (p < 0.05 for each model). Reduced physical component summary score of SF-36 over follow-up was independently associated with decreased SPPB score (p < 0.020), muscle CSA (p < 0.046), and increased 400 m walk time (p < 0.003). CONCLUSIONS: In older adults with and without mobility limitations, declining muscle mass, strength, power, and physical performance contribute independently to increase FoF, while declines of muscle mass and physical performance contribute to deterioration of QoL. These findings provide further rationale for developing interventions to improve aging muscle health.

A founder mutation in the TCIRG1 gene causes osteopetrosis in the Ashkenazi Jewish population.

Osteopetrosis is a rare and heterogeneous genetic disorder characterized by dense bone mass that is a consequence of defective osteoclast function and/or development. Autosomal recessive osteopetrosis (ARO) is the most severe form and is often fatal within the first years of life; early hematopoietic stem cell transplant (HSCT) remains the only curative treatment for ARO. The majority of the ARO-causing mutations are located in the TCIRG1 gene. We report here the identification and characterization of an A to T transversion in the fourth base of the intron 2 donor splice site (c.117+4A→T) in TCIRG1, a mutation not previously seen in the Ashkenazi Jewish (AJ) population. Analysis of a random sample of individuals of AJ descent revealed a carrier frequency of approximately 1 in 350. Genotyping of five loci adjacent to the c.117+4A→T-containing TCIRG1 allele revealed that the presence of this mutation in the AJ population is due to a single founder. The identification of this mutation will enable population carrier testing and will facilitate the identification and treatment of individuals homozygous for this mutation.

Lower extremity muscle mass predicts functional performance in mobility-limited elders.

OBJECTIVES: This study examined the influence of lower extremity body composition and muscle strength on the severity of mobility-disability in community-dwelling older adults. METHODS: Fifty-seven older males and females (age 74.2 +/- 7 yrs; BMI 28.9 +/- 6 kg/m2) underwent an objective assessment of lower extremity functional performance, the Short Physical Performance Battery test (SPPB). Participants were subsequently classified as having moderate (SPPB score 7: n = 38) or severe mobility impairments (SPPB score

Haemodynamic determinants of elevated pulse wave velocity during acute isometric handgrip exercise.

BACKGROUND: Measurement of pulse wave velocity (PWV) provides a reliable index of vascular stiffness. Despite its widespread application, the physiological interrelationships between PWV, blood pressure (BP) and in particular, heart rate (HR), have yet to be fully elucidated. Furthermore, little is known about altered arterial compliance during acute exercise. AIM: To examine the effects of 3-min supine non-dominant isometric handgrip exercise (ISOMEX), performed at 30% of maximum voluntary contraction, on carotid-radial PWV, BP and HR in the dominant arm of 51 healthy subjects. RESULTS: During exercise, PWV correlated strongly with diastolic BP (r = 0.55, p < 0.01) and mean arterial pressure (r = 0.51, p < 0.01). PWV and HR failed to correlate at rest or during exercise. CONCLUSION: ISOMEX invoked an elevated PWV, which is predominantly related to BP or factors determining it, and not HR. The carotid-radial PWV stress test is a simple measurement that may have prognostic potential for use in large-scale population studies.