Publications

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.

BACKGROUND: Evaluating handgrip strength (HGS) asymmetry may help to improve the prognostic value of HGS. This study sought to determine the associations of HGS asymmetry and weakness on future activities of daily living (ADL) disability in a national sample of aging Americans. METHODS: The analytic sample included 18,468 Americans aged >/=50 years from the 2006-2016 waves of the Health and Retirement Study. A handgrip dynamometer measured HGS. Those with HGS >10% stronger on either hand were considered as having any HGS asymmetry. Individuals with HGS >10% stronger on their dominant hand were considered as having dominant HGS asymmetry, while those with HGS >10% stronger on their nondominant hand were classified as having nondominant HGS asymmetry. Men with HGS 26 kg and women with HGS 16 kg were considered weak. ADLs were self-reported. Generalized estimating equations were used for analyses. RESULTS: Relative to those with symmetric HGS and no weakness, each HGS asymmetry and weakness group had increased odds for future ADL disability: 1.11 (95% confidence interval [CI]: 1.02-1.20) for any HGS asymmetry alone, 1.42 (CI: 1.16-1.74) for weakness alone, and 1.81 (CI: 1.52-2.16) for both any HGS asymmetry and weakness. Most weakness and HGS asymmetry dominance groups had increased odds for future ADL disability: 1.30 (CI: 1.13-1.50) for nondominant HGS asymmetry alone, 1.42 (CI: 1.16-1.74) for weakness alone, 1.72 (CI: 1.29-2.29) for both weakness and nondominant HGS asymmetry, and 1.86 (CI: 1.52-2.28) for both weakness and dominant HGS asymmetry. CONCLUSIONS: HGS asymmetry and weakness together may increase the predictive utility of handgrip dynamometers.

Maximal handgrip strength (HGS) is a convenient and reliable, but incomplete, assessment of muscle function. Although low HGS is a powerful predictor of poor health, several limitations to maximal HGS exist. The predictive value of HGS is restricted because low HGS is associated with a wide range of unspecified health conditions, and other characteristics of muscle function aside from strength capacity are not evaluated. Current HGS protocol guidelines emphasize the ascertainment of maximal force, which is only a single muscle function characteristic. Muscle function is intrinsically multivariable, and assessing other attributes in addition to strength capacity will improve screenings for age-related disabilities and diseases. Digital handgrip dynamometers and accelerometers provide unique opportunities to examine several aspects of muscle function beyond strength capacity, while also maintaining procedural ease. Specifically, digital handgrip dynamometry and accelerometry can assess the rate of force development, submaximal force steadiness, fatigability, and task-specific tremoring. Moreover, HGS protocols can be easily refined to include an examination of strength asymmetry and bilateral strength. Therefore, evaluating muscle function with new HGS technologies and protocols may provide a more comprehensive assessment of muscle function beyond maximal strength, without sacrificing feasibility. This Special Article introduces a novel framework for assessing multiple attributes of muscle function with digital handgrip dynamometry, accelerometry, and refinements to current HGS protocols. Such framework may aid in the discovery of measures that better predict and explain age-related disability, biological aging, and the effects of comorbid diseases that are amenable to interventions. These additional HGS measures may also contribute to our understanding of concepts such as resilience. Using sophisticated HGS technologies that are currently available and modernizing protocols for developing a new muscle function assessment may help transform clinical practice by enhancing screenings that will better identify the onset and progression of the disabling process.

BACKGROUND: Dementia screening is an important step for appropriate dementia-related referrals to diagnosis and treat possible dementia. OBJECTIVE: We sought to estimate the prevalence of no reported dementia-related diagnosis in a nationally representative sample of older Americans with a cognitive impairment consistent with dementia (CICD). METHODS: The weighted analytical sample included 6,036,224 Americans aged at least 65 years old that were identified as having a CICD without history of stroke, cancers, neurological conditions, or brain damage who participated in at least one-wave of the 2010-2016 Health and Retirement Study. The adapted Telephone Interview of Cognitive Status assessed cognitive functioning. Those with scores

BACKGROUND: Examining handgrip strength (HGS) asymmetry could extend the utility of handgrip dynamometers for screening future falls. AIMS: We sought to determine the associations of HGS asymmetry on future falls in older Americans. METHODS: The analytic sample included 10,446 adults aged at least 65 years from the 2006-2016 waves of the Health and Retirement Study. Falls were self-reported. A handgrip dynamometer measured HGS. The highest HGS on each hand was used for determining HGS asymmetry ratio: (non-dominant HGS/dominant HGS). Those with HGS asymmetry ratio 1.0 had their ratio inverted to make all HGS asymmetry ratios >/= 1.0. Participants were categorized into asymmetry groups based on their inverted HGS asymmetry ratio: (1) 0.0-10.0%, (2) 10.1-20.0%, (3) 20.1-30.0%, and (4) > 30.0%. Generalized estimating equations were used for the analyses. RESULTS: Every 0.10 increase in HGS asymmetry ratio was associated with 1.26 (95% confidence interval (CI) 1.07-1.48) greater odds for future falls. Relative to those with HGS asymmetry 0.0-10.0%, participants with HGS asymmetry > 30.0% had 1.15 (CI 1.01-1.33) greater odds for future falls; however, the associations were not significant for those with HGS asymmetry 10.1-20.0% (odds ratio: 1.06; CI 0.98-1.14) and 20.1-30.0% (odds ratio: 1.10; CI 0.99-1.22). Compared to those with HGS asymmetry 0.0-10.0%, participants with HGS asymmetry > 10.0% and > 20.0% had 1.07 (CI 1.01-1.16) and 1.12 (CI 1.02-1.22) greater odds for future falls, respectively. DISCUSSION: Asymmetric HGS, as a possible biomarker of impaired neuromuscular function, may help predict falls. CONCLUSIONS: We recommend that HGS asymmetry be considered in HGS protocols and fall risk assessments.

BACKGROUND: Serum zinc (Zn) levels have been shown to be associated with functional status; however, it is not clear whether this association differs by other sociodemographic characteristics. We examined the association between serum Zn levels and physical functioning difficulty in a representative sample of older adults in the US. DESIGN AND METHODS: A cross-sectional study was conducted on participants 50 years and older from the 2011-12 and 2013-14 National Health and Nutrition Examination Surveys (n = 1136). Serum Zn levels were analyzed as tertiles. The main outcome of interest was physical functioning difficulty, defined as self-reported difficulty of basic physical functioning that included walking, transferring, dressing, and feeding. RESULTS: Mean Zn levels (SE) were 0.67(0.1), 0.81(0.1), and 0.98(0.1) mug/mL in the low, middle, and high Zn groups, respectively. Approximately 24.9% participants reported physical functioning difficulty. In the multivariable model, we found a significant multiplicative interaction between sex and serum Zn (P for interaction =0.028) and between education and serum Zn (P for interaction = 0.001) on basic physical functioning difficulty. The stratified analysis revealed that among men, compared to those with low serum Zn, the odds of having physical functioning difficulty were lower in men who had high serum Zn [aOR 0.43 (95% CI: 0.25-0.76)]. For women, compared to those with low serum Zn the odds of having physical functioning difficulty were higher in women who had middle serum Zn [aOR 2.67 (1.58-4.50)]. Among individuals with less than high school education, the odds of having physical functioning difficulty were lower in those who had middle serum Zn compared to those who had low serum Zn [aOR 0.48 (0.26-0.89)]. However, the odds of having physical functioning difficulty were higher in those who had middle serum Zn compared to those who had low serum Zn for individuals with high school [aOR 5.72 (1.92-17.00)] and beyond high school education [aOR 1.77 (1.05-2.97)], respectively. CONCLUSION: Sex and educational attainment interact with serum Zn levels to influence basic physical functioning difficulty in older adults.

BACKGROUND: Despite surgical reconstruction and extensive rehabilitation, persistent quadriceps inhibition, gait asymmetry, and functional impairment remain prevalent in patients after anterior cruciate ligament (ACL) injury. A combination of reports have suggested underlying central nervous system adaptations in those after injury govern long-term neuromuscular impairments. The classic assumption has been to attribute neurophysiologic deficits to components of injury, but other factors across the continuum of care (e.g. surgery, perioperative analgesia, and rehabilitative strategies) have been largely overlooked. OBJECTIVE: This review provides a multidisciplinary perspective to 1) provide a narrative review of studies reporting neuroplasticity following ACL injury in order to inform clinicians of the current state of literature and 2) provide a mechanistic framework of neurophysiologic deficits with potential clinical implications across all phases of injury and recovery (injury, surgery, and rehabilitation) RESULTS: Studies using a variety of neurophysiologic modalities have demonstrated peripheral and central nervous system adaptations in those with prior ACL injury. Longitudinal investigations suggest neurophysiologic changes at spinal-reflexive and corticospinal pathways follow a unique timecourse across injury, surgery, and rehabilitation. CONCLUSION: Clinicians should consider the unique injury, surgery, anesthesia, and rehabilitation on central nervous system adaptations. Therapeutic strategies across the continuum of care may be beneficial to mitigate maladaptive neuroplasticity in those after ACL injury.

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 degrees /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). 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.

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.

Skeletal muscle function deficits associated with advancing age are due to several physiological and morphological changes including loss of muscle size and quality (conceptualized as a reduction in the intrinsic force-generating capacity of a muscle when adjusted for muscle size). Several factors can contribute to loss of muscle quality, including denervation, excitation-contraction uncoupling, increased fibrosis, and myosteatosis (excessive levels of inter- and intramuscular adipose tissue and intramyocellular lipids). These factors also adversely affect metabolic function. There is a major unmet need for tools to rapidly and easily assess muscle mass and quality in clinical settings with minimal patient and provider burden. Herein, we discuss the potential for electrical impedance myography (EIM) as a tool to evaluate muscle mass and quality in older adults. EIM applies weak, non-detectible (e.g., 400 muA), mutifrequency (e.g., 1 kHz-1 MHz) electrical currents to a muscle (or muscle group) through two excitation electrodes, and resulting voltages are measured via two sense electrodes. Measurements are fast ( 5 s/muscle), simple to perform, and unaffected by factors such as hydration that may affect other simple measures of muscle status. After nearly 2 decades of study, EIM has been shown to reflect muscle health status, including the presence of atrophy, fibrosis, and fatty infiltration, in a variety of conditions (e.g., developmental growth and maturation, conditioning/deconditioning, and obesity) and neuromuscular diseases states [e.g., amyotrophic lateral sclerosis (ALS) and muscular dystrophies]. In this article, we describe prior work and current evidence of EIM's potential utility as a measure of muscle health in aging and geriatric medicine.