Publications

2019

Wages, N. P., B. C. Clark, C. R. Criss, and D. R. Grooms. 2019. “Neuroanatomy and physiology of the motor control and corticobulbar systems”. Current Trends in Neurology 12: 1-22.

This article provides an overview of the pathways the nervous system uses to create movement, and apply this knowledge to explain current therapeutic interventions for functional rehabilitation. The first section focuses on motor control hierarchy, where we describe how the motor system is organized in a conceptual hierarchical system to communicate across the central and peripheral nervous systems. The second section focuses on preparation and initiation of voluntary movement, where we explain the function of distinct regions of the brain, and how those regions consolidate and integrate their processing to engage in motor planning, formation and initiation of movement commands, and organization of sequential motor actions. The third section focuses on descending motor pathways, where we provide an anatomical description of how motor neurons navigate the various descending pathways from the cerebrum, or brainstem, to innervate their bodily targets. The fourth section focuses on feedforward and feedback mechanisms, where we discuss how sensory feedback and feedforward mechanisms impact movement regulation. The fifth section focuses on neural development of motor control, where we explain the basic developmental properties of motor control, from embryological development through adult maturation. The last section focuses on therapeutic approaches to motor rehabilitation, where we describe current therapeutic strategies clinicians use to enhance sensory, motor, and cognitive abilities for rehabilitation.

Chen, H., Y. Han, I. Jahan, S. Wu, B. C. Clark, and J. S. Wiseman. 2019. “Extracts of Maca (Lepidium meyenii) Root Inhibit Mitochondrial Function and Induce Increased Glucose Uptake in an Adipocyte Cell Line”. Journal of Herbal Medicine 17-18: 100282.

The authors describe the effects of an ethanol extract of maca root on glucose uptake and metabolism in cultured 3T3-L1 adipocytes. The extract stimulates glucose uptake and shares many features of an insulin mimetic: increased phosphorylation of insulin receptor (IR), increased phosphorylation of Akt downstream of IR, and inhibition of glucose uptake by LY294002, an inhibitor of PI3K, which mediates Akt phosphorylation. However, the extract also inhibits mitochondrial oxygen consumption. The effect on glucose uptake is biphasic, and inhibition of mitochondrial respiration is associated with decreased glucose uptake at high concentrations. When the authors examined the effects of a well-characterized mitochondrial poison, oligomycin, for comparison, completely parallel effects on the insulin signaling pathway and the same biphasic effect on glucose uptake were observed. It is concluded that stimulation of the insulin pathway by the extract is an indirect effect of mitochondrial inhibition rather than direct stimulation of the pathway itself. These results have practical implications for assessing the potential benefit of natural products in glucose homeostasis and caution against concentrated extracts from maca for use in humans.

Tavoian, D., D. W. Russ, T. D. Law, J. E. Simon, P. J. Chase, E. H. Guseman, and B. C. Clark. 2019. “A Randomized Clinical Trial Comparing Three Different Exercise Strategies for Optimizing Aerobic Capacity and Skeletal Muscle Performance in Older Adults: Protocol for the DART Study”. Front Med (Lausanne) 6: 236. https://doi.org/10.3389/fmed.2019.00236.
Background: Age-related declines in physical function lead to decreased independence and higher healthcare costs. Individuals who meet the endurance and resistance exercise recommendations can improve their physical function and overall fitness, even into their ninth decade. However, most older adults do not exercise regularly, and the majority of those who do only perform one type of exercise, and in doing so are not getting the benefits of endurance or resistance exercise. Herein we present the study protocol for a randomized clinical trial that will investigate the potential for high-intensity interval training (HIIT) to improve maximal oxygen consumption, muscular power, and muscle volume (primary outcomes), as well as body composition, 6-min walk distance, and muscular strength and endurance (secondary outcomes). Methods and Analysis: This is a single-site, single-blinded, randomized clinical trial. A minimum of 24 and maximum of 30 subjects aged 60-75 that are generally healthy but insufficiently active will be randomized. After completion of baseline assessments, participants will be randomized in a 1:1:1 ratio to participate in one of three 12-week exercise programs: stationary bicycle HIIT, stationary bicycle moderate-intensity continuous training (MICT), or resistance training. Repeat assessments will be taken immediately post intervention. Discussion: This study will examine the potential for stationary bicycle HIIT to result in both cardiorespiratory and muscular adaptations in older adults. The results will provide important insights into the effectiveness of interval training, and potentially support a shift from volume-driven to intensity-driven exercise strategies for older adults. Clinical Trial Registration: This trial is registered with ClinicalTrials.gov (registration number: NCT03978572, date of registration June 7, 2019).
Tavoian, D., K. Ampomah, S. Amano, T. D. Law, and B. C. Clark. 2019. “Changes in DXA-derived lean mass and MRI-derived cross-sectional area of the thigh are modestly associated”. Sci Rep 9: 10028. https://doi.org/10.1038/s41598-019-46428-w.
Dual-energy X-ray absorptiometry (DXA) derived measures of lean mass demonstrate strong associations with magnetic resonance imaging (MRI) derived measures of muscle volume (MV) in cross-sectional studies, however, few studies have compared changes in response to an intervention. The purpose of this study was to determine the accuracy of DXA at detecting changes in lean mass, using MRI-derived MV as a reference standard. 10 male and 16 female subjects (29.2 +/- 9.5 years) underwent DXA and MRI scans before and after a 10-week resistance training intervention. DXA thigh lean mass was compared to MRI mid-thigh MV, and percent change in size was compared between MRI and DXA. There was a strong correlation between measures cross-sectionally (r = 0.89) in agreement with previous investigations. However, there was a modest correlation of percentage change over time between methods (r = 0.49). Bland-Altman plots revealed that the amount of random error increased as the magnitude of the change from baseline increased. DXA measures of change in lean mass were modestly associated with MRI measures of change in MV. While there are several advantages to using DXA for the measurement of lean mass, the inability to accurately detect changes over time calls into question its use in clinical trials.
Smith, J. W., Knight Davis, C. C. Quatman-Yates, B. L. Waterman, S. A. Strassels, J. D. Wong, V. K. Heh, et al. 2019. “Loss of Community-Dwelling Status Among Survivors of High-Acuity Emergency General Surgery Disease”. J Am Geriatr Soc 67: 2289-97. https://doi.org/10.1111/jgs.16046.
OBJECTIVES: To examine loss of community-dwelling status 9 months after hospitalization for high-acuity emergency general surgery (HA-EGS) disease among older Americans. DESIGN: Retrospective analysis of claims data. SETTING: US communities with Medicare beneficiaries. PARTICIPANTS: Medicare beneficiaries age 65 years or older hospitalized urgently/emergently between January 1, 2015, and March 31, 2015, with a principal diagnosis representing potential life or organ threat (necrotizing soft tissue infections, hernias with gangrene, ischemic enteritis, perforated viscus, toxic colitis or gastroenteritis, peritonitis, intra-abdominal hemorrhage) and an operation of interest on hospital days 1 or 2 (N = 3319). MEASUREMENTS: Demographic characteristics (age, race, and sex), comorbidities, principal diagnosis, complications, and index hospitalization disposition (died; discharged to skilled nursing facility [SNF], long-term acute care [LTAC], rehabilitation, hospice, home (with or without services), or acute care hospital; other) were measured. Survivors of index hospitalization were followed until December 31, 2015, on mortality and community-dwelling status (SNF/LTAC vs not). Descriptive statistics, Kaplan-Meier plots, and chi(2) tests were used to describe and compare the cohort based on disposition. A multivariable logistic regression model, adjusted for age, sex, comorbidities, complications, and discharge disposition, determined independent predictors of loss of community-dwelling status at 9 months. RESULTS: A total of 2922 (88%) survived index hospitalization. Likelihood of discharge to home decreased with increasing age, baseline comorbidities, and in-hospital complications. Overall, 418 (14.3%) HA-EGS survivors died during the follow-up period. Among those alive at 9 months, 10.3% were no longer community dwelling. Initial discharge disposition to any location other than home and three or more surgical complications during index hospitalization were independent predictors of residing in a SNF/LTAC 9 months after surviving HA-EGS. CONCLUSION: Older Americans, known to prioritize living in the community, will experience substantial loss of independence due to HA-EGS. Long-term expectations after surviving HA-EGS must be framed from the perspective of the outcomes that older patients value the most. Further research is needed to examine the quality-of-life burden of EGS survivorship prospectively. J Am Geriatr Soc 67:2289-2297, 2019.
Oki, K., L. A. Clark, S. Amano, and B. C. Clark. 2019. “Effect of Anodal Transcranial Direct Current Stimulation of the Motor Cortex on Elbow Flexor Muscle Strength in the Very Old”. J Geriatr Phys Ther 42: 243-48. https://doi.org/10.1519/JPT.0000000000000145.
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.
McGrath, R. P., B. C. Clark, K. M. Erlandson, S. D. Herrmann, B. M. Vincent, O. T. Hall, and K. J. Hackney. 2019. “Impairments in Individual Autonomous Living Tasks and Time to Self-Care Disability in Middle-Aged and Older Adults”. J Am Med Dir Assoc 20: 730-735 e3. https://doi.org/10.1016/j.jamda.2018.10.014.
OBJECTIVES: Impairments in specific tasks that are necessary for independent living may identify future self-care limitations, and the use of time-varying covariates can better capture the fluidity in functional capacity trajectories over time. The purpose of this study was to determine the associations between individual instrumental activities of daily living (IADL) impairments and time to activities of daily living (ADL) disability for middle-aged and older adults in the United States. DESIGN: Longitudinal panel. SETTING: Detailed interviews that included physical, biological, and psychosocial measures were completed in person. The core interview was typically completed over the telephone. PARTICIPANTS: A nationally representative sample of 15,336 adults aged at least 50 years from the 2006 wave of the Health and Retirement Study was followed for 8 years. MEASURES: Ability to perform IADL and ADL were self-reported at each wave. Separate covariate-adjusted Cox models were used to examine the time-varying associations between individual IADL impairments and time to ADL disability. RESULTS: The presence of each IADL impairment was associated with a higher hazard ratio for an ADL disability for the following functions: 2.52 [95% confidence interval (CI) 2.35, 2.70] for grocery shopping, 1.91 (CI 1.77, 2.06) for preparing hot meals, 1.55 (CI 1.37, 1.76) for taking medications, 1.48 (CI 1.36, 1.61) for managing money, 1.41 (CI 1.27, 1.57) for using a telephone, and 1.38 (CI 1.29, 1.48) for using a map. CONCLUSIONS/IMPLICATIONS: Our findings provide insights into the disabling process by revealing how impairments in each IADL are differentially associated with time to ADL disability. Interventions aiming to retain function during aging should be informed by fluctuations in IADL performance and how specific IADL impairments may exacerbate functional capacity declines more so than others.
McGrath, R., S. G. Robinson-Lane, S. Cook, B. C. Clark, S. Herrmann, M. L. O’Connor, and K. J. Hackney. 2019. “Handgrip Strength Is Associated with Poorer Cognitive Functioning in Aging Americans”. J Alzheimers Dis 70: 1187-96. https://doi.org/10.3233/JAD-190042.
BACKGROUND: Measures of handgrip strength may show promise for detecting cognitive erosion during aging. OBJECTIVE: To determine the associations between lower handgrip strength and poorer cognitive functioning for aging Americans. METHODS: There were 13,828 participants aged at least 50 years from the 2006 wave of the Health and Retirement Study included and followed biennially for 8 years. Handgrip strength was assessed with a hand-held dynamometer and cognitive functioning was assessed with a modified version of the Mini-Mental State Examination. Participants aged 65 years with scores 7- 11 had a mild cognitive impairment, /=65 years with scores 8- 10 had a mild cognitive impairment,
McGrath, R., K. M. Erlandson, B. M. Vincent, K. J. Hackney, S. D. Herrmann, and B. C. Clark. 2019. “Decreased Handgrip Strength is Associated With Impairments in Each Autonomous Living Task for Aging Adults in the United States”. J Frailty Aging 8: 141-45. https://doi.org/10.14283/jfa.2018.47.
OBJECTIVES: The primary purpose of this study was to determine the time-varying associations between decreased handgrip strength (HGS) and individual instrumental activities of daily living (IADL) impairments for a nationally-representative sample of aging adults in the United States. DESIGN: Longitudinal-Panel. SETTING: Detailed interviews were completed in person and core interviews were typically completed over the telephone. PARTICIPANTS: A total of 15,336 participants aged at least 50 years who participated in the 2006 wave of the Health and Retirement Study were followed biennially for 8-years. MEASUREMENTS: A hand-held dynamometer assessed HGS and performance in IADLs were self-reported. RESULTS: Every 5-kilogram decrease in HGS was associated with an increased odds ratio for the following IADL impairments: 1.11 (95% confidence interval (CI): 1.09, 1.13) for using a map, 1.10 (CI: 1.07, 1.12) for grocery shopping, 1.09 (CI: 1.05, 1.14) for taking medications, 1.07 (CI: 1.05, 1.09) for preparing hot meals, 1.06 (CI: 1.04, 1.08) for managing money, and 1.05 (CI: 1.02, 1.09) for using a telephone. CONCLUSIONS: Decreased HGS was associated with each IADL impairment, and slightly different associations were observed in individual IADL tasks for aging adults in the United States. Our findings suggest that decreased HGS, which is reflective of reduced function of the neuromuscular system, is associated with diminished performance in autonomous living tasks during aging. Losses in HGS may lead to the development of an IADL impairment. Therefore, health-care providers working with aging adults should utilize measures of HGS as a screening tool for identifying future deficits in neuromuscular functioning. Interventions designed to preserve IADLs in aging adults should also include measures of HGS for detecting early changes in IADL capacity, and intervening at the onset of HGS declines may help aging adults retain their ability to live autonomously.