mmPose-FK: A Forward Kinematics Approach to Dynamic Skeletal Pose Estimation Using mmWave Radars.

In this paper, we propose mmPose-FK, a novel millimeter wave (mmWave) radar-based pose estimation method that employs a dynamic forward kinematics (FK) approach to address the challenges posed by low resolution, specularity, and noise artifacts commonly associated with mmWave radars. These issues often result in unstable joint poses that vibrate over time, reducing the effectiveness of traditional pose estimation techniques. To overcome these limitations, we integrate the FK mechanism into the deep learning model and develop an end-to-end solution driven by data. Our comprehensive experiments using various matrices and benchmarks highlight the superior performance of mmPose-FK, especially when compared to our previous research methods. The proposed method provides more accurate pose estimation and ensures increased stability and consistency, which underscores the continuous improvement of our methodology, showcasing superior capabilities over its antecedents. Moreover, the model can output joint rotations and human bone lengths, which could be further utilized for various applications such as gait parameter analysis and height estimation. This makes mmPose-FK a highly promising solution for a wide range of applications in the field of human pose estimation and beyond.

Physical and Cognitive Function Assessment to Predict Postoperative Outcomes of Abdominal Surgery.

BACKGROUND: Current evaluation methods to assess physical and cognitive function are limited and often not feasible in emergency settings. The upper-extremity function (UEF) test to assess physical and cognitive performance using wearable sensors. The purpose of this study was to examine the (1) relationship between preoperative UEF scores with in-hospital outcomes; and (2) association between postoperative UEF scores with 30-d adverse outcomes among adults undergoing emergent abdominal surgery. METHODS: We performed an observational, longitudinal study among adults older than 40 y who presented with intra-abdominal symptoms. The UEF tests included a 20-sec rapid repetitive elbow flexion (physical function), and a 60-sec repetitive elbow flexion at a self-selected pace while counting backwards by threes (cognitive function), administered within 24-h of admission and within 24-h prior to discharge. Multiple logistic regression models assessed the association between UEF and outcomes. Each model consisted of the in-hospital or 30-d post-discharge outcome as the dependent variable, preoperative UEF physical and cognitive scores as hypothesis covariates, and age and sex as adjuster covariates. RESULTS: Using UEF physical and cognitive scores to predict in-hospital outcomes, an area under curve (AUC) of 0.76 was achieved, which was 17% more sensitive when compared to age independently. For 30-d outcomes, the AUC increased to 0.89 when UEF physical and cognitive scores were included in the model with age and sex. DISCUSSION: Sensor-based measures of physical and cognitive function enhance outcome prediction providing an objective practicable tool for risk stratification in emergency surgery settings among aging adults presenting with intra-abdominal symptoms.

An assisted living interprofessional education and practice geriatric screening clinic (IPEP-GSC): a description and evaluation.

As the U.S. population ages and lives longer, we need to assure that future providers are prepared to work in highly functioning interprofessional teams to deliver person-centered care for older adults with complex chronic conditions. Assisted living facilities are ideal venues in which to train interprofessional health sciences students in providing such care. After monthly clinics involving interprofessional students (from the colleges of medicine, nursing, pharmacy, public health, and school of social work) providing team-based care to older adults, students' post-clinic evaluations indicated perceived improvements in knowledge, attitudes, and perceptions about aging and care of older adults. In addition, participating older adults reported improved self-worth and enjoyment. The curriculum, evaluation outcomes, and lessons learned are described to support program replication.

Failure to Rescue After Emergency General Surgery in Geriatric Patients: Does Frailty Matter?

BACKGROUND: Failure to rescue (FTR) is considered as an index of quality of care provided by a hospital. However, the role of frailty in FTR remains unclear. We hypothesized that the FTR rate is higher for frail geriatric emergency general surgery (EGS) patients than nonfrail geriatric EGS patients. METHODS: We performed a 3-y (2015-2017) prospective cohort study of all geriatric patients (age ≥ 65 y) requiring EGS. Frailty was calculated by using the EGS-specific Frailty Index (EGSFI) within 24 h of admission. Patients were divided into two groups: frail (FI ≥ 0.325) and nonfrail (FI < 0.325). We defined FTR as death from a major complication. Regression analysis was performed to control for demographics, type of operative intervention, admission vitals, and admission laboratory values. RESULTS: Three hundred twenty-six geriatric EGS patients were included, of which 38.9% were frail. Frail patients were more likely to be white (P < 0.01) and, on admission, had a higher American Association of Anesthesiologist class (P = 0.03) and lower serum albumin (P < 0.01). However, there was no difference between the groups regarding age (P = 0.54), gender (P = 0.56), admission vitals, and WBC count (P = 0.35). Overall, 26.7% (n = 85) of patients developed in-hospital complications; and mortality occurred in 30% (n = 26) of those patients (i.e., the FTR group). Frail patients had higher rates of FTR (14% vs. 4%, P < 0.001) than nonfrail patients. On regression analysis, after controlling for confounders, frail status was an independent predictor of FTR (OR: 3.4 [2.3-4.6]) in geriatric EGS patients. CONCLUSIONS: Our study demonstrates that in geriatric EGS patients, a frail status independently contributes to FTR and increases the odds of FTR threefold compared with nonfrail status. Thus, it should be included in quality metrics for geriatric EGS patients.

Variation in use of antipsychotic medications in nursing homes in the United States: A systematic review.

BACKGROUND: The use of antipsychotic medications (APMs) in nursing home residents in the U.S. is an increasingly prominent issue and has been associated with increased risk of hospitalization, cardiovascular events, hip fractures, and mortality, among other adverse health events. The Food and Drug Administration has placed a black box warning on these drugs, specifying that they are not meant for residents with dementia, and has asked providers to review their treatment plans. The purpose of this systematic PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses)-based review was to summarize original research studies on facility level characteristics contributing to the use of antipsychotics in nursing homes across the United States, in order to investigate the variation of use. METHODS: We searched Ovid Medline, Embase, Cochrane Library, Web of Science, CINAHL, PsycInfo, and Sociological Abstracts. Articles were selected according to the following criteria: (1) Population of interest: older adults (≥60 years of age) residing in nursing homes (not home-based or inpatient hospital settings) in the U.S. (2) Receiving APMs, typical and/or atypical. Specifically excluded were studies of psychotropic medications such as antidepressants, benzodiazepines, anxiolytics, hypnotics, mood stabilizers, and stimulants. All study designs were considered, though reviews, editorials, letters to the editor and opinion pieces were excluded. An expert consultant panel was consulted to categorize facility characteristics into domains and determine possible etiologies of APM use based upon each characteristic. RESULTS: Nineteen observational studies, both quantitative and qualitative, published from 2000 to 2015, met full inclusion criteria and were included in this review. APM use varied based on multiple facility characteristics across several domains: 1) physical, 2) staffing, 3) occupancy, 4) market, and 5) quality. CONCLUSIONS: Variation in use of APMs in U.S. nursing homes based upon facility characteristics exemplifies the need for a more systematic protocol guiding the use of these medications, along with heightened regulatory policies and enforcement.

Multi-parametric MR imaging of quadriceps musculature in the setting of clinical frailty syndrome.

OBJECTIVE: Frailty is a common geriatric syndrome associated with loss of skeletal muscle mass (sarcopenia) conferring an increased risk of rapid decline in health and function with increased vulnerability to adverse outcomes. The purpose of this study was to investigate the correlation between diffusion tensor, T2 and intramuscular fat content values of the quadriceps muscle group and clinical frailty status using diffusion tensor MR imaging. MATERIAL AND METHODS: Subjects were recruited from the Arizona Frailty cohort composed of all females with frailty status based on the Fried criteria, including 6 non-frail and 10 pre-frail/frail adults, as well as a community sample of 11 young, healthy controls. Axial images of both thighs were obtained on a 3-T magnet with T1, T2 and diffusion tensor imaging as well as intramuscular fat analysis. Diffusion tensor and T2 values were determined by region-of-interest measurements at the proximal, mid and distal thirds of both thighs. Data were evaluated to determine differences between measured values and frailty status. RESULTS: The mean fractional anisotropy (FA) values in the bilateral quadriceps muscles demonstrated significant differences (F = 7.558, p = 0.0030) between the control and pre-frail/frail and non-frail and pre-frail/frail groups. There was a significant difference in mean T2 (F = 21.675, p < 0.0001) and lipid content (F = 19.266, p < 0.0001) among all three groups in the total quadriceps muscle group. CONCLUSION: The quadriceps musculature of pre-frail/frail adults demonstrated increased FA compared to young controls and non-frail adults with increasing T2 and intramuscular fat among the control, non-frail and pre-frail/frail categories.

Predictors of Prolonged Length of Stay and Adverse Events among Older Adults with Behavioral Health-Related Emergency Department Visits: A Systematic Medical Record Review.

BACKGROUND: Behavioral health (BH)-related visits to the emergency department (ED) by older adults are increasing. This population has unique challenges to providing quality, timely care. OBJECTIVE: To characterize older adults with BH-related ED visits and determine risk factors associated with prolonged length of stay (LOS) and adverse events (AEs). METHODS: We performed a retrospective electronic health record review of all patients ≥65 years who presented to our ED from September 2011 to August 2012 for BH-related complaints. Sociodemographic, clinical, and utilization data were tested for association with LOS and AE. RESULTS: The 213 elder BH patients represented 4% of the 5267 total elder visits during the study period. Median age was 75 (interquartile range [IQR] 70-82); largely white (84.5%), female (58.7%), and non-Hispanic (69.5%). There was a median of two comorbidities (IQR 1-3), and 46.9% were cognitively impaired. Most (71.5%) were being evaluated on an involuntary basis. Median LOS was 16.2 h (IQR 9.7-29.7). Increased LOS was associated with involuntary status (12.4 h, 95% confidence interval [95% CI] 6.4-18.4); use of restraints (11.9 h, 95% CI 5.7-18.2); and failed discharge (28.8 h, 95% CI 21.2-36.6). For every 10 additional hours in the ED, the risk for an AEs (p = .002) or potential AEs (p = .01) increased 20%. CONCLUSION: Elderly ED patients with BH complaints had high rates of cognitive impairment and multiple comorbidities. LOS was prolonged, and there were multiple contributing factors including involuntary status, chemical or physical restraint, and failed discharge. Patients with longer LOS were at increased risk of an AE or potentially AEs.

Wearable sensor-based in-home assessment of gait, balance, and physical activity for discrimination of frailty status: baseline results of the Arizona frailty cohort study.

BACKGROUND: Frailty is a geriatric syndrome resulting from age-related cumulative decline across multiple physiologic systems, impaired homeostatic reserve, and reduced capacity to resist stress. Based on recent estimates, 10% of community-dwelling older individuals are frail and another 41.6% are prefrail. Frail elders account for the highest health care costs in industrialized nations. Impaired physical function is a major indicator of frailty, and functional performance tests are useful for the identification of frailty. Objective instrumented assessments of physical functioning that are feasible for home frailty screening have not been adequately developed. OBJECTIVE: To examine the ability of wearable sensor-based in-home assessment of gait, balance, and physical activity (PA) to discriminate between frailty levels (nonfrail, prefrail, and frail). METHODS: In an observational cross-sectional study, in-home visits were completed in 125 older adults (nonfrail: n=44, prefrail: n=60, frail: n=21) living in Tucson, Ariz., USA, between September 2012 and November 2013. Temporal-spatial gait parameters (speed, stride length, stride time, double support, and variability of stride velocity), postural balance (sway of hip, ankle, and center of mass), and PA (percentage of walking, standing, sitting, and lying; mean duration and variability of single walking, standing, sitting, and lying bouts) were measured in the participant's home using validated wearable sensor technology. Logistic regression was used to assess the most sensitive gait, balance, and PA variables for identifying prefrail participants (vs. nonfrail). Multinomial logistic regression was used to identify variables sensitive to discriminate between three frailty levels. RESULTS: Gait speed (area under the curve, AUC=0.802), hip sway (AUC=0.734), and steps/day (AUC=0.736) were the most sensitive parameters for the identification of prefrailty. Multinomial regression revealed that stride length (AUC=0.857) and double support (AUC=0.841) were the most sensitive gait parameters for discriminating between three frailty levels. Interestingly, walking bout duration variability was the most sensitive PA parameter for discriminating between three frailty levels (AUC=0.818). No balance parameter discriminated between three frailty levels. CONCLUSION: Our results indicate that unique parameters derived from objective assessment of gait, balance, and PA are sensitive for the identification of prefrailty and the classification of a subject's frailty level. The present findings highlight the potential of wearable sensor technology for in-home assessment of frailty status.

Regulation of Cardiac Autonomic Nervous System Control across Frailty Statuses: A Systematic Review.

BACKGROUND: Frailty is a geriatric syndrome that leads to impairment in interrelated physiological systems and progressive homeostatic dysregulation in physiological systems. OBJECTIVE: The focus of the present systematic review was to study the association between the activity of the cardiac autonomic nervous system (ANS) and frailty. METHODS: A systematic literature search was conducted in multiple databases: PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials.gov; the last search was performed in March 2015. Inclusion criteria were: (1) that the studied population was classified for frailty according to a standard definition, such as Fried's criteria; (2) that the study had a nonfrail control group, and (3) that heart rate (HR) and/or heart rate variability (HRV) were parameters of interest in the study. RESULTS: Of the 1,544 articles screened, 54 were selected for full-text review and 6 studies met the inclusion criteria. Assessment of HRV using different standard time domain, frequency domain, and nonlinear domain approaches confirmed the presence of an impaired cardiac ANS function in frail compared to nonfrail participants. Furthermore, HR changes while performing a clinical test (e.g., the seated step test or the lying-to-standing orthostatic test) were decreased in the frail group compared to the nonfrail group. CONCLUSIONS: The current systematic review provides evidence that the cardiac ANS is impaired in frail compared to nonfrail older adults, as indicated by a reduction in the complexity of HR dynamics, reduced HRV, and reduced HR changes in response to daily activities. Four out of 6 included articles recruited only female participants, and in the other 2 articles the effect of gender on impairment of cardiac ANS was insufficiently investigated. Therefore, further studies are required to study the association between cardiac ANS impairments and frailty in males. Furthermore, HRV was studied only during static postures such as sitting, or without considering the level of activity as a potential confounder. Accordingly, simultaneous measurement of both physiological (i.e., HRV) and kinematic (e.g., using wearable sensor technology) information may provide a better understanding of cardiac ANS impairments with frailty while controlling for activity.

The impact of cochlear implantation on cognition in older adults: a systematic review of clinical evidence.

BACKGROUND: Hearing loss is the third most prevalent chronic condition faced by older adults and has been linked to difficulties in speech perception, activities of daily living, and social interaction. Recent studies have suggested a correlation between severity of hearing loss and an individual's cognitive function; however, a causative link has yet to be established. One intervention option for management of the most severe to profound hearing loss in older adults is cochlear implantation. We performed a review to determine the status of the literature on the potential influence of cochlear implantation on cognition in the older adult population. METHODS: Over 3800 articles related to cochlear implants, cognition, and older adults were reviewed. Inclusion criteria were as follows: (1) study population including adults > 65 years, (2) intervention with cochlear implantation, and (3) cognition as the primary outcome measure of implantation. RESULTS: Out of 3,886 studies selected, 3 met inclusion criteria for the review. CONCLUSIONS: While many publications have shown that cochlear implants improve speech perception, social functioning, and overall quality of life, we found no studies in the English literature that have prospectively evaluated changes in cognitive function after implantation with modern cochlear implants in older adults. The state of the current literature reveals a need for further clinical research on the impact of cochlear implantation on cognition in older adults.

Development of an Enhanced Interprofessional Chief Resident Immersion Training (IP-CRIT) Program.

Using interprofessional faculty, the authors reviewed and enhanced the nationally renowned Chief Resident Immersion Training (CRIT) in the Care of Older Adults Program to include Triple Aim objectives and interprofessional competency-based content and developed the Interprofessional CRIT. Evaluations were positive and sustained. The authors educated chief residents about value-based care, linking them to key interprofessional staff to build team-based care. The authors addressed quality improvement issues identified by the Institute of Medicine and our health network. Chief residents are now better prepared to train medical students and residents using a team-based, patient-centered approach, and a culture of continual quality improvement toward improved care of older patients.

Post-acute sequelae of SARS-CoV-2 infection (Long COVID) in older adults.

Long COVID, also known as PASC (post-acute sequelae of SARS-CoV-2), is a complex infection-associated chronic condition affecting tens of millions of people worldwide. Many aspects of this condition are incompletely understood. Among them is how this condition may manifest itself in older adults and how it might impact the older population. Here, we briefly review the current understanding of PASC in the adult population and examine what is known on its features with aging. Finally, we outline the major gaps and areas for research most germane to older adults.

Longitudinal Assessment of Mobility and Self-care Among Critically Ill Older Adults. An Age-Friendly Health Systems Initiative Quality Improvement Study.

BACKGROUND: Early mobility in the intensive care unit (ICU) is vital to maintaining an older adult patient's performance of activities of daily living, functional mobility, and overall quality of life. Prior studies have shown reduced length of inpatient stay and onset of delirium in patients with early mobilization. Despite these benefits, many ICU patients are often labeled as too sick to participate in therapy and frequently do not receive physical (PT) or occupational therapy (OT) consults until they are considered floor status. This delay in therapy can negatively affect a patient's capacity to participate in his/her self-care, add to the burden on caregivers, and limit disposition options. OBJECTIVES: Our goals were to perform a longitudinal assessment of mobility and self-care among older patients through their medical ICU (MICU) stays and to quantify visits by therapy services to identify areas for improvement in achieving early intervention in this at-risk population. METHOD: This was a retrospective quality improvement analysis of a cohort of admissions to the MICU at a large tertiary academic medical center between November 2018 and May 2019. Admission information, PT and OT consult information, Perme Intensive Care Unit Mobility Score, and Modified Barthel Index scores were entered into a quality improvement registry. Inclusion criteria consisted of age older than 65 years and at least 2 distinct visits by PT and/or OT for evaluation. Patients without consults and patients with weekend-only MICU stays were not assessed. RESULTS: There were 302 MICU patients 65 years or older admitted during the study period. Forty-four percent (132) of these patients received PT/OT consults, and among these, 32% (42) had at least 2 visits to allow comparison of objective scores. Seventy-five percent of patients had improved Perme scores (median, 9.4%; interquartile range, 2.3%-15.6%), and 58% of patients had improved Modified Barthel Index scores (median, 3%; interquartile range, -2% to 13.5%). However, 17% of potential therapy days were missed because of inadequate staffing/time, and 14% were missed because of being sedated or unable to participate. CONCLUSIONS: In our cohort of patients older than 65 years, receipt of therapy in the MICU led to modest improvements in score-assessed mobility and self-care before transfer to floor. Staffing, time constraints, and patient sedation or encephalopathy appeared to interfere most with further potential benefits. In the next phase, we plan to implement strategies to increase PT/OT availability in the MICU and implement a protocol to increase identification and referral of candidates for whom early therapy can prevent loss of mobility and ability to perform self-care.

Frailty Identification Using Heart Rate Dynamics: A Deep Learning Approach.

Previous research showed that frailty can influence autonomic nervous system and consequently heart rate response to physical activities, which can ultimately influence the homeostatic state among older adults. While most studies have focused on resting state heart rate characteristics or heart rate monitoring without controlling for physical activities, the objective of the current study was to classify pre-frail/frail vs non-frail older adults using heart rate response to physical activity (heart rate dynamics). Eighty-eight older adults (≥65 years) were recruited and stratified into frailty groups based on the five-component Fried frailty phenotype. Groups consisted of 27 non-frail (age = 78.80±7.23) and 61 pre-frail/frail (age = 80.63±8.07) individuals. Participants performed a normal speed walking as the physical task, while heart rate was measured using a wearable electrocardiogram recorder. After creating heart rate time series, a long short-term memory model was used to classify participants into frailty groups. In 5-fold cross validation evaluation, the long short-term memory model could classify the two above-mentioned frailty classes with a sensitivity, specificity, F1-score, and accuracy of 83.0%, 80.0%, 87.0%, and 82.0%, respectively. These findings showed that heart rate dynamics classification using long short-term memory without any feature engineering may provide an accurate and objective marker for frailty screening.

The association between heart rate behavior and gait performance: The moderating effect of frailty.

INTRODUCTION: Research suggests that frailty not only influence individual systems, but also it affects the interconnection between them. However, no study exists to show how the interplay between cardiovascular and motor performance is compromised with frailty. AIM: To investigate the effect of frailty on the association between heart rate (HR) dynamics and gait performance. METHODS: Eighty-five older adults (≥65 years and able to walk 9.14 meters) were recruited (October 2016-March 2018) and categorized into 26 non-frail (age = 78.65±7.46 years) and 59 pre-frail/frail individuals (age = 81.01±8.17) based on the Fried frailty phenotype. Participants performed gait tasks while equipped with a wearable electrocardiogram (ECG) sensor attached to the chest, as well as wearable gyroscopes for gait assessment. HR dynamic parameters were extracted, including time to peak HR and percentage increase in HR in response to walking. Using the gyroscope sensors gait parameters were recorded including stride length, stride velocity, mean swing velocity, and double support. RESULTS: Among the pre-frail/frail group, time to peak HR was significantly correlated with all gait parameters (p<0.0001, r = 0.51-0.59); however, for the non-frail group, none of the correlations between HR dynamics and gait performance parameters were significant (p>0.45, r = 0.03-0.15). The moderation analysis of time to peak HR, demonstrated a significant interaction effect of HR dynamics and frailty status on walking velocity (p<0.01), and the interaction effect was marginally non-significant for other gait parameters (p>0.10). CONCLUSIONS: Current findings, for the first time, suggest that a compromised motor and cardiac autonomic interaction exist among pre-frail/frail older adults; an impaired HR performance (i.e., slower increase of HR in response to stressors) may lead to a slower walking performance. Assessing physical performance and its corresponding HR behavior should be studied as a tool for frailty screening and providing insights about the underlying cardiovascular-related mechanism leading to physical frailty.

Brain function complexity during dual-tasking is associated with cognitive impairment and age.

BACKGROUND AND PURPOSE: Early diagnosis of cognitive impairment is important because symptoms can be delayed through therapies. Synaptic disconnections are the key characteristics of dementia, and through nonlinear complexity analysis of brain function, it is possible to identify long-range synaptic disconnections in the brain. METHODS: We investigated the capability of a novel upper-extremity function (UEF) dual-task paradigm in the functional MRI (fMRI) setting, where the participant flexes and extends their arm while counting, to differentiate between cognitively normal (CN) and those with mild cognitive impairment (MCI). We used multiscale entropy (MSE) complexity analysis of the blood oxygen-level dependent time-series across neural networks and brain regions. Outside of the fMRI, we used the UEF dual-task test, while the elbow kinematics were measured using motion sensors, to record the motor function score. RESULTS: Results showed 34% lower MSE values in MCI compared to CN (p<.04 for all regions and networks except cerebellum when counting down by one; effect size = 1.35±0.15) and a negative correlation between MSE values and age (average r2 of 0.30 for counting down by one and 0.36 for counting backward by three). Results also showed an improvement in the logistic regression model sensitivity by 14-24% in predicting the presence of MCI when brain function measure was added to the motor function score (kinematics data). CONCLUSIONS: Current findings suggest that combining measures of neural network and motor function, in addition to neuropsychological testing, may provide an accurate tool for assessing early-stage cognitive impairment and age-related decline in cognition.

Mechanisms of Racial Disparities in Cognitive Aging: An Examination of Material and Psychosocial Well-Being.

OBJECTIVES: We tested the hypothesis that education's effect on cognitive aging operates in part through measures of material and psychosocial well-being. METHOD: Our sample was of non-Latino black and white participants of the National Social Life Health and Aging Project who had valid cognitive assessments in Waves 2 and 3 (n = 2,951; age range: 48-95). We used structural equation modeling to test for mediation and moderated mediation by income, assets, perceived stress, social status, and allostatic load on the relationships between race, education, and cognition at two time points. RESULTS: Education consistently mediated the race-cognition relationship, explaining about 20% of the relationship between race and cognition in all models. Income and assets were moderated by race; these factors were associated with cognition for whites but not blacks. Social status mediated the association between race and cognition, and social status and perceived stress mediated the education-cognition pathway. Allostatic load was not a mediator of any relationship. DISCUSSION: Education remains the best explanatory factor for cognitive aging disparities, though material well-being and subjective social status help to explain a portion of the racial disparity in cognitive aging.

IL-6 can singlehandedly drive many features of frailty in mice.

Frailty is a geriatric syndrome characterized by age-related declines in function and reserve resulting in increased vulnerability to stressors. The most consistent laboratory finding in frail subjects is elevation of serum IL-6, but it is unclear whether IL-6 is a causal driver of frailty. Here, we characterize a new mouse model of inducible IL-6 expression (IL-6TET-ON/+ mice) following administration of doxycycline (Dox) in food. In this model, IL-6 induction was Dox dose-dependent. The Dox dose that increased IL-6 levels to those observed in frail old mice directly led to an increase in frailty index, decrease in grip strength, and disrupted muscle mitochondrial homeostasis. Littermate mice lacking the knock-in construct failed to exhibit frailty after Dox feeding. Both naturally old mice and young Dox-induced IL-6TET-ON/+ mice exhibited increased IL-6 levels in sera and spleen homogenates but not in other tissues. Moreover, Dox-induced IL-6TET-ON/+ mice exhibited selective elevation in IL-6 but not in other cytokines. Finally, bone marrow chimera and splenectomy experiments demonstrated that non-hematopoietic cells are the key source of IL-6 in our model. We conclude that elevated IL-6 serum levels directly drive age-related frailty, possibly via mitochondrial mechanisms.

Frailty Syndrome, Cognition, and Dysphonia in the Elderly.

PURPOSE: The purpose of the current study is to determine the relation of frailty syndrome to acoustic measures of voice quality and voice-related handicap. METHODS: Seventy-three adults (52 community-dwelling participants and 21 assisted living residents) age 60 and older completed frailty screening, acoustic assessment, cognitive screening, and the Voice Handicap Index-10 (VHI-10). Factor analysis was used to consolidate acoustic measures. Statistical analysis included multiple regression, analysis of variance, and Tukey post-hoc tests with alfa of 0.05. RESULTS: Montreal Cognitive Assessment (MoCA) and exhaustion explained 28% of the variance in VHI-10. MoCA and sex explained 27% of the variance in factor 1 (spectral ratio), age and MoCA explained 13% of the variance in factor 2 (cepstral peak prominence for speech), and slowness explained 10% of the variance in factor 3 (cepstral peak prominence for sustained /a/). There were statistically significant differences in two measures across frailty groups: VHI-10 and MoCA. Acoustic factor scores did not differ significantly among frailty groups (P > 0.05). CONCLUSIONS: Voice-related handicap and cognitive status differed among robust and frail older adults, yet vocal function measures did not. The components of frailty most related to VHI-10 were exhaustion and weight loss rather than slowness, weakness, or inactivity. Based on these findings, routine screening of physical frailty and cognition are recommended as part of a complete voice evaluation for older adults.