Fracture discrimination capability of ulnar flexural rigidity measured via Cortical Bone Mechanics Technology: study protocol for The STRONGER Study.

Osteoporosis is characterized by low bone mass and structural deterioration of bone tissue, which leads to bone fragility (ie, weakness) and an increased risk for fracture. The current standard for assessing bone health and diagnosing osteoporosis is DXA, which quantifies areal BMD, typically at the hip and spine. However, DXA-derived BMD assesses only one component of bone health and is notably limited in evaluating the bone strength, a critical factor in fracture resistance. Although multifrequency vibration analysis can quickly and painlessly assay bone strength, there has been limited success in advancing a device of this nature. Recent progress has resulted in the development of Cortical Bone Mechanics Technology (CBMT), which conducts a dynamic 3-point bending test to assess the flexural rigidity (EI) of ulnar cortical bone. Data indicate that ulnar EI accurately estimates ulnar whole bone strength and provides unique and independent information about cortical bone compared to DXA-derived BMD. Consequently, CBMT has the potential to address a critical unmet need: Better identification of patients with diminished bone strength who are at high risk of experiencing a fragility fracture. However, the clinical utility of CBMT-derived EI has not yet been demonstrated. We have designed a clinical study to assess the accuracy of CBMT-derived ulnar EI in discriminating post-menopausal women who have suffered a fragility fracture from those who have not. These data will be compared to DXA-derived peripheral and central measures of BMD obtained from the same subjects. In this article, we describe the study protocol for this multi-center fracture discrimination study (The STRONGER Study).

Reductions in Motor Unit Firing are Associated with Clinically Meaningful Leg Extensor Weakness in Older Adults.

Weakness, one of the key characteristics of sarcopenia, is a significant risk factor for functional limitations and disability in older adults. It has long been suspected that reductions in motor unit firing rates (MUFRs) are one of the mechanistic causes of age-related weakness. However, prior work has not investigated the extent to which MUFR is associated with clinically meaningful weakness in older adults. Forty-three community-dwelling older adults (mean: 75.4 ± 7.4 years; 46.5% female) and 24 young adults (mean: 22.0 ± 1.8 years; 58.3% female) performed torque matching tasks at varying submaximal intensities with their non-dominant leg extensors. Decomposed surface electromyographic recordings were used to quantify MUFRs from the vastus lateralis muscle. Computational modeling was subsequently used to independently predict how slowed MUFRs would negatively impact strength in older adults. Bivariate correlations between MUFRs and indices of lean mass, voluntary activation, and physical function/mobility were also assessed in older adults. Weak older adults (n = 14) exhibited an approximate 1.5 and 3 Hz reduction in MUFR relative to non-weak older adults (n = 29) at 50% and 80% MVC, respectively. Older adults also exhibited an approximate 3 Hz reduction in MUFR relative to young adults at 80% MVC only. Our model predicted that a 3 Hz reduction in MUFR results in a strength decrement of 11-26%. Additionally, significant correlations were found between slower MUFRs and poorer neuromuscular quality, voluntary activation, chair rise time performance, and stair climb power (r's = 0.31 to 0.43). These findings provide evidence that slowed MUFRs are mechanistically linked with clinically meaningful leg extensor weakness in older adults.

Comparison of strategies for assessment of rate of torque development in older and younger adults.

There is increasing appreciation of the role of rate of torque development (RTD) in physical function of older adults (OAs). This study compared various RTD strategies and electromyography (EMG) in the knee extensors and focused on discriminating groups with potential limitations in voluntary activation (VA) and associations of different RTD indices with functional tests that may be affected by VA in OAs. Neuromuscular function was assessed in 20 younger adults (YAs, 22.0 ± 1.7 years) and 50 OAs (74.4 ± 7.0 years). Isometric ballistic and peak torque during maximal voluntary contractions (pkTMVC), doublet stimulation and surface EMG were assessed and used to calculate VA during pkTMVC and RTD and rate of EMG rise during ballistic contractions. Select mobility tests (e.g., gait speed, 5× chair rise) were also assessed in the OAs. Voluntary RTD and RTD normalized to pkTMVC, doublet torque, and peak doublet RTD were compared. Rate of EMG rise and voluntary RTD normalized to pkTMVC did not differ between OAs and YAs, nor were they associated with functional test scores. Voluntary RTD indices normalized to stimulated torque parameters were significantly associated with VA (r = 0.319-0.459), and both indices were significantly lower in OAs vs YAs (all p < 0.020). These RTD indices showed significant association with the majority of mobility tests, but there was no clear advantage among them. Thus, voluntary RTD normalized to pkTMVC was ill-suited for use in OAs, while results suggests that voluntary RTD normalized to stimulated torque parameters may be useful for identifying central mechanisms of RTD impairment in OAs.Clinical trial registration number NCT02505529; date of registration 07/22/2015.

The relation of ApoE and COMT gene-gene interactions to cognitive and motor function in community-dwelling older adults: a pilot study.

Introduction: Certain genes increase the risk of age-related neurological dysfunction and/or disease. For instance, ApoE is a well-known gene carrying risk for Alzheimer's disease, while COMT has been associated with age-related reductions in motor function. There is growing interest in the interrelationship between age-related changes in cognitive and motor function, and examining gene-gene interactions in this context. In this pilot study we examined the relations of the ApoE and COMT genes and their interaction to both cognitive and motor performance in community-dwelling older adults. Methods: We leveraged an archived dataset from a prior study on age-related muscle weakness in community-dwelling older adults. Sample size was between 72 and 82 individuals based on missing data. We examined the relationship of ApoE (Ɛ4 presence/absence), rs4680 SNP on the COMT gene (Val/Met, Val/Val, Met/Met), and sex on (1) overall cognitive functioning and specific cognitive domains known to decline in aging (processing speed, immediate and delayed memory, semantic and phonemic fluency, and executive functioning), and (2) indices of motor function (four square step test, short physical performance battery, grip strength/forearm lean mass, and purdue pegboard test). Results: Homozygous COMT genotypes were associated with worse global cognitive performance, immediate memory, and semantic fluency, but only for older adults with at least one ApoE Ɛ4 allele. There were main effects for COMT for delayed memory and a main effect for both COMT and ApoE for coding and phonemic fluency. Women scored higher than men in overall cognition, immediate and delayed memory, and semantic fluency. There were no main effects or gene interactions for a measure of executive functioning (trial making test part B) or any of the measures of motor function. Discussion: COMT, ApoE, and their interaction influence cognitive performance, but not motor functioning, in community dwelling older adults. Our work supports prior literature concluding that a heterozygous COMT genotype may be beneficial to sustain healthy cognitive functioning with advancing age for those who have a higher ApoE genetic risk status (at least one Ɛ4 allele). Future research should investigate interactions between COMT and ApoE in larger samples with comprehensive assessment of cognition and motor functioning.

Discrepancies in hand motor performance and executive function in older adults.

There is increasing interest in using motor function tests to identify risk of cognitive impairment in older adults (OA). This study examined associations among grip strength, with and without adjustment for muscle mass, manual dexterity and Trail Making Test (TMT) A and B in 77 OA (73.4 ± 5.2 years) with globally intact cognition. A subset of OA who exhibited mismatched motor function (e.g., in the highest strength and lowest dexterity tertiles, or vice versa) was identified and analyzed. Dexterity showed stronger associations with TMT-A and -B than grip strength (absolute or adjusted). OA with mismatched motor function scored worse on tests of TMT-B, but not -A than those with matched motor function. Dexterity may have more promise than grip strength for identifying increased risk of cognitive impairment. Intriguing, though limited, data suggest that mismatched motor function (strength vs. dexterity) in OAs might be an even more robust marker of such risk.

Brain-Predicted Age Difference Moderates the Association Between Muscle Strength and Mobility.

BACKGROUND: Approximately 35% of individuals over age 70 report difficulty with mobility. Muscle weakness has been demonstrated to be one contributor to mobility limitations in older adults. The purpose of this study was to examine the moderating effect of brain-predicted age difference (an index of biological brain age/health derived from structural neuroimaging) on the relationship between leg strength and mobility. METHODS: In community dwelling older adults (N = 57, 74.7 ± 6.93 years; 68% women), we assessed the relationship between isokinetic leg extensor strength and a composite measure of mobility [mobility battery assessment (MBA)] using partial Pearson correlations and multifactorial regression modeling. Brain predicted age (BPA) was calculated from T1 MR-images using a validated machine learning Gaussian Process regression model to explore the moderating effect of BPA difference (BPAD; BPA minus chronological age). RESULTS: Leg strength was significantly correlated with BPAD (r = -0.317, p < 0.05) and MBA score (r = 0.541, p < 0.001). Chronological age, sex, leg strength, and BPAD explained 63% of the variance in MBA performance (p < 0.001). BPAD was a significant moderator of the relationship between strength and MBA, accounting for 7.0% of MBA score variance [△R 2 = 0.044, F(1,51) = 6.83, p = 0.01]. Conditional moderation effects of BPAD indicate strength was a stronger predictor of mobility in those with a great BPAD. CONCLUSION: The relationship between strength and mobility appears to be influenced by brain aging, with strength serving as a possible compensation for decline in neural integrity.

Heterogeneity of the strength response to progressive resistance exercise training in older adults: Contributions of muscle contractility.

BACKGROUND: Older adults display wide individual variability (heterogeneity) in the effects of resistance exercise training on muscle strength. The mechanisms driving this heterogeneity are poorly understood. Understanding of these mechanisms could permit development of more targeted interventions and/or improved identification of individuals likely to respond to resistance training interventions. Thus, this study assessed potential physiological factors that may contribute to strength response heterogeneity in older adults: neural activation, muscle hypertrophy, and muscle contractility. METHODS: In 24 older adults (72.3 ± 6.8 years), we measured the following parameters before and after 12 weeks of progressive resistance exercise training: i) isometric leg extensor strength; ii) isokinetic (60°/sec) leg extensor strength; iii) voluntary (neural) activation by comparing voluntary and electrically-stimulated muscle forces (i.e., superimposed doublet technique); iv) muscle hypertrophy via dual-energy x-ray absorptiometry (DXA) estimates of regional lean tissue mass; and v) intrinsic contractility by electrically-elicited twitch and doublet torques. We examined associations between physiological factors (baseline values and relative change) and the relative change in isometric and isokinetic muscle strength. RESULTS: Notably, changes in quadriceps contractility were positively associated with the relative improvement in isokinetic (r = 0.37-0.46, p ≤ 0.05), but not isometric strength (r = 0.09-0.21). Change in voluntary activation did not exhibit a significant association with the relative improvements in either isometric or isokinetic strength (r = 0.35 and 0.33, respectively; p > 0.05). Additionally, change in thigh lean mass was not significantly associated with relative improvement in isometric or isokinetic strength (r = 0.09 and -0.02, respectively; p > 0.05). Somewhat surprising was the lack of association between exercise-induced changes in isometric and isokinetic strength (r = 0.07). CONCLUSIONS: The strength response to resistance exercise in older adults appears to be contraction-type dependent. Therefore, future investigations should consider obtaining multiple measures of muscle strength to ensure that strength adaptations are comprehensively assessed. Changes in lean mass did not explain the heterogeneity in strength response for either contraction type, and the data regarding the influence of voluntary activation was inconclusive. For isokinetic contraction, the strength response was moderately explained by between-subject variance in the resistance-exercise induced changes in muscle contractility.

Reduced Neural Excitability and Activation Contribute to Clinically Meaningful Weakness in Older Adults.

BACKGROUND: Weakness is a risk factor for physical limitations and death in older adults (OAs). We sought to determine whether OAs with clinically meaningful leg extensor weakness exhibit differences in voluntary inactivation (VIA) and measures of corticospinal excitability when compared to young adults (YAs) and OAs without clinically meaningful weakness. We also sought to estimate the relative contribution of indices of neural excitability and thigh lean mass in explaining the between-subject variability in OAs leg extensor strength. METHODS: In 66 OAs (75.1 ± 7.0 years) and 20 YAs (22.0 ± 1.9 years), we quantified leg extensor strength, thigh lean mass, VIA, and motor evoked potential (MEP) amplitude and silent period (SP) duration. OAs were classified into weakness groups based on previously established strength/body weight (BW) cut points (Weak, Modestly Weak, or Not Weak). RESULTS: The OAs had 63% less strength/BW when compared to YAs. Weak OAs exhibited higher levels of leg extensor VIA than Not Weak OAs (14.2 ± 7.5% vs 6.1 ± 7.5%). Weak OAs exhibited 24% longer SPs compared to Not Weak OAs, although this difference was insignificant (p = .06). The Weak OAs MEPs were half the amplitude of the Not Weak OAs. Regression analysis indicated that MEP amplitude, SP duration, and thigh lean mass explained ~62% of the variance in strength, with the neural excitability variables explaining ~33% of the variance and thigh lean mass explaining ~29%. CONCLUSION: These findings suggest that neurotherapeutic interventions targeting excitability could be a viable approach to increase muscle strength in order to reduce the risk of physical impairments in late life.

Is impaired dopaminergic function associated with mobility capacity in older adults?

The capacity to move is essential for independence and declines with age. Slow movement speed, in particular, is strongly associated with negative health outcomes. Prior research on mobility (herein defined as movement slowness) and aging has largely focused on musculoskeletal mechanisms and processes. More recent work has provided growing evidence for a significant role of the nervous system in contributing to reduced mobility in older adults. In this article, we report four pieces of complementary evidence from behavioral, genetic, and neuroimaging experiments that, we believe, provide theoretical support for the assertion that the basal ganglia and its dopaminergic function are responsible, in part, for age-related reductions in mobility. We report four a posteriori findings from an existing dataset: (1) slower central activation of ballistic force development is associated with worse mobility among older adults; (2) older adults with the Val/Met intermediate catecholamine-O-methyl-transferase (COMT) genotype involved in dopamine degradation exhibit greater mobility than their homozygous counterparts; (3) there are moderate relationships between performance times from a series of lower and upper extremity tasks supporting the notion that movement speed in older adults is a trait-like attribute; and (4) there is a relationship of functional connectivity within the medial orbofrontal (mOFC) cortico-striatal network and measures of mobility, suggesting that a potential neural mechanism for impaired mobility with aging is the deterioration of the integrity of key regions within the mOFC cortico-striatal network. These findings align with recent basic and clinical science work suggesting that the basal ganglia and its dopaminergic function are mechanistically linked to age-related reductions in mobility capacity.

Development of a trunk motor paradigm for use in neuroimaging.

The purpose of this study was to quantify head motion between isometric erector spinae (ES) contraction strategies, paradigms, and intensities in the development of a neuroimaging protocol for the study of neural activity associated with trunk motor control in individuals with low back pain. Ten healthy participants completed two contraction strategies; (1) a supine upper spine (US) press and (2) a supine lower extremity (LE) press. Each contraction strategy was performed at electromyographic (EMG) contraction intensities of 30, 40, 50, and 60% of an individually determined maximum voluntary contraction (MVC) (±10% range for each respective intensity) with real-time, EMG biofeedback. A cyclic contraction paradigm was performed at 30% of MVC with US and LE contraction strategies. Inertial measurement units (IMUs) quantified head motion to determine the viability of each paradigm for neuroimaging. US vs LE hold contractions induced no differences in head motion. Hold contractions elicited significantly less head motion relative to cyclic contractions. Contraction intensity increased head motion in a linear fashion with 30% MVC having the least head motion and 60% the highest. The LE hold contraction strategy, below 50% MVC, was found to be the most viable trunk motor control neuroimaging paradigm.

Relative contribution of muscle strength, lean mass, and lower extremity motor function in explaining between-person variance in mobility in older adults.

BACKGROUND: Approximately 35% of individuals > 70 years have mobility limitations. Historically, it was posited lean mass and muscle strength were major contributors to mobility limitations, but recent findings indicate lean mass and muscle strength only moderately explain mobility limitations. One likely reason is that lean mass and muscle strength do not necessarily incorporate measures globally reflective of motor function (defined as the ability to learn, or to demonstrate, the skillful and efficient assumption, maintenance, modification, and control of voluntary postures and movement patterns). In this study we determined the relative contribution of lean mass, muscle strength, and the four square step test, as an index of lower extremity motor function, in explaining between-participant variance in mobility tasks. METHODS: In community-dwelling older adults (N = 89; 67% women; mean 74.9 ± 6.7 years), we quantified grip and leg extension strength, total and regional lean mass, and time to complete the four square step test. Mobility was assessed via 6-min walk gait speed, stair climb power, 5x-chair rise time, and time to complete a complex functional task. Multifactorial linear regression modeling was used to determine the relative contribution (via semi-partial r2) for indices of lean mass, indices of muscle strength, and the four square step test. RESULTS: When aggregated by sex, the four square step test explained 17-34% of the variance for all mobility tasks (p <  0.01). Muscle strength explained ~ 12% and ~ 7% of the variance in 6-min walk gait speed and 5x-chair rise time, respectively (p <  0.02). Lean mass explained 32% and ~ 4% of the variance in stair climb power and complex functional task time, respectively (p <  0.02). When disaggregated by sex, lean mass was a stronger predictor of mobility in men. CONCLUSION: The four square step test is uniquely associated with multiple measures of mobility in older adults, suggesting lower extremity motor function is an important factor for mobility performance. TRIAL REGISTRATION: NCT02505529 -2015/07/22.

The Aging Brain & the Dorsal Basal Ganglia: Implications for Age-Related Limitations of Mobility.

The capacity to move is essential for independence and declines with age. Limitations in mobility impact ~35% of adults over 70 and the majority of adults over 85. These limitations are highly associated with disability, dependency, and survival. More than 25-years ago the term "sarcopenia" was coined to highlight the age-related loss of muscle mass and strength with the assumption being that sarcopenia led to limitations in mobility. However, contrary to expectations, recent findings clearly indicate these variables only modestly explain limitations in mobility. One likely reason the current sarcopenia variables of muscle mass and strength do not discriminate, or predict, mobility limitations well is because they are heavily influenced by musculoskeletal mechanisms and do not incorporate measures reflective of the central neural control of mobility. Unfortunately, the precise central neural changes associated with aging that lead to decreased mobility are poorly understood. This knowledge gap has hampered the development of effective interventions for mobility limitations and the subsequent reduction of major functional disability for older adults. Here, we discuss the potential role of the motor control circuit of the dorsal basal ganglia as well as dopaminergic function in age-related reductions in mobility.

Effect of Anodal Transcranial Direct Current Stimulation of the Motor Cortex on Elbow Flexor Muscle Strength in the Very Old.

BACKGROUND AND PURPOSE: Muscle weakness predisposes older adults to a fourfold increase in functional limitations and has previously been associated with reduced motor cortex excitability in aging adults. The purpose of this study was to determine whether a single session of anodal transcranial direct current stimulation (tDCS) of the motor cortex would increase elbow flexion muscle strength and electromyographic (EMG) amplitude in very old individuals. METHODS: Eleven very old individuals-85.8 (4.3) years-performed 3 maximal isometric elbow flexion contractions before and after 20 minutes of sham or anodal tDCS on different days. Order of stimulation was randomized, and the study participants and investigators were blinded to condition. In addition, voluntary activation capacity of the elbow flexors was determined by comparing voluntary and electrically evoked forces. RESULTS: Anodal tDCS did not alter muscle strength or EMG activity in comparison to sham stimulation. Elbow flexion voluntary activation capacity was very high among the study participants: 99.3% (1.8%). CONCLUSION: Contrary to our hypothesis, we observed no effect of anodal tDCS and no impairment in elbow flexor voluntary activation capacity in the very old. Whether anodal tDCS would exert a positive effect and support our initial hypothesis in another muscle group that does exhibit impairments in voluntary activation in older adults is a question that is still to be addressed.

Resistance Exercise to Prevent and Manage Sarcopenia and Dynapenia.

For well over twenty centuries the muscle wasting (sarcopenia) and weakness (dynapenia) that occurs with old age has been a predominant concern of mankind. Exercise has long been suggested as a treatment to combat sarcopenia and dynapenia, as it exerts effects on both the nervous and muscular systems that are critical to positive physiological and functional adaptations (e.g., enhanced muscle strength). For more than two decades scientists have recognized the profound role that progressive resistance exercise training can have on increasing muscle strength, muscle size and functional capacity in older adults. In this review article we discuss how resistance exercise training can be used in the management and prevention of sarcopenia and dynapenia. We first provide an overview of the evidence for this notion and highlight certain critical factors- namely exercise intensity, volume and progression- that are key to optimizing the resistance exercise prescription. We then highlight how many, if not most, of the commonly prescribed exercise programs for seniors are not the 'best practices', and subsequently present easy-to-read guidelines for a well-rounded resistance exercise training program designed for the management and prevention of sarcopenia and dynapenia, including example training programs for the beginner through the advanced senior resistance exerciser. These guidelines have been written for the academician as well as the student and health care provider across a variety of disciplines, including those in the long term care industry, such as wellness instructors or activity directors.