Design and Methods of the Early Age-Related Hearing Loss Investigation Randomized Controlled Trial.

OBJECTIVE: Hearing loss has been identified as a major modifiable risk factor for cognitive decline. The Early Age-Related Hearing Loss Investigation (EARHLI) study will assess the mechanisms linking early age-related hearing loss (ARHL) and cognitive impairment. STUDY DESIGN: Randomized, controlled, single-site, early phase II, superiority trial. SETTING: Tertiary academic medical center. PARTICIPANTS: One hundred fifty participants aged 55 to 75 years with early ARHL (severity defined as borderline to moderate) and amnestic mild cognitive impairment will be included. INTERVENTIONS: Participants will be randomized 1:1 to a best practice hearing intervention or a health education control. MAIN OUTCOME MEASURES: The primary study outcome is cognition measured by the Alzheimer Disease Cooperative Study-Preclinical Alzheimer Cognitive Composite. Secondary outcomes include additional measures of cognition, social engagement, and brain organization/connectivity. RESULTS: Trial enrollment will begin in early 2024. CONCLUSIONS: After its completion in 2028, the EARHLI trial should offer evidence on the effect of hearing treatment versus a health education control on cognitive performance, social engagement, and brain organization/connectivity in 55- to 75-year-old community-dwelling adults with early ARHL and amnestic mild cognitive impairment.

Hearing Impairment and Physical Activity and Physical Functioning in Older Adults: Baseline Results from the ACHIEVE Trial.

BACKGROUND: Hearing loss is associated with restricted physical activity (PA) and impaired physical functioning, yet the relationship between severity of hearing impairment (HI) and novel PA measures in older adults with untreated HI is not well understood. METHODS: Analyses included 845 participants aged ≥70 years (mean=76.6y) with a better-hearing ear pure-tone average (PTA) ≥30 and <70 dB in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study who wore an ActiGraph accelerometer for 7 days. Physical functioning measures included grip strength and the Short Physical Performance Battery (SPPB). Linear regression models estimated the association by HI level (moderate or greater [PTA≥40 dB] vs. mild [PTA<40 dB]) and continuous hearing with total daily activity counts, active minutes/day, activity fragmentation, grip strength, and gait speed. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of poor performance on the SPPB (≤6) and its subtests (≤2). Mixed-effects models estimated differences by HI level in activity by time of day. RESULTS: Participants with moderate or greater HI had poorer physical functioning, particularly balance (OR=2.17, 95% CI=1.29-3.67), vs. those with mild impairment. There was no association of HI level with activity quantities or fragmentation. For diurnal patterns of activity, participants with moderate or greater HI had fewer activity counts in the afternoon (12:00pm-05:59pm). CONCLUSIONS: Older adults with worse hearing had shifted diurnal patterns and poorer balance performance. Exercise programs should be tailored to older adults with different levels of HI to maintain PA and physical functioning, particularly balance control.

Cardiopulmonary Exercise Testing in a Prospective Multicenter Cohort of Older Adults.

PURPOSE: Cardiorespiratory fitness (CRF) measured by peak oxygen consumption (VO 2 peak) declines with aging and correlates with mortality and morbidity. Cardiopulmonary Exercise Testing (CPET) is the criterion method to assess CRF, but its feasibility, validity and reliability in older adults is unclear. Our objective was to design and implement a dependable, safe and reliable CPET protocol in older adults. METHODS: VO 2 peak was measured by CPET, performed using treadmill exercise in 875 adults ≥70 years in the Study of Muscle, Mobility and Aging (SOMMA). The protocol included a symptom-limited peak (maximal) exercise and two submaximal walking speeds. An adjudication process was in place to review tests for validity if they met any prespecified criteria [VO 2 peak < 12.0 ml/kg/min; maximum heart rate (HR) <100 bpm; respiratory exchange ratio (RER) <1.05 and a rating of perceived exertion <15]. A subset (N = 30) performed a repeat test to assess reproducibility. RESULTS: CPET was safe and well tolerated, with 95.8% of participants able to complete the VO 2 peak phase of the protocol. Only 56 (6.4%) participants had a risk alert and only two adverse events occurred: a fall and atrial fibrillation. Mean ± SD VO 2 peak was 20.2 ± 4.8 mL/kg/min, peak HR 142 ± 18 bpm, and peak RER 1.14 ± 0.09. Adjudication was indicated in 47 tests; 20 were evaluated as valid, 27 as invalid (18 data collection errors, 9 did not reach VO 2 peak). Reproducibility of VO 2 peak was high (intraclass correlation coefficient = 0.97). CONCLUSIONS: CPET was feasible, effective and safe for older adults, including many with multimorbidity or frailty. These data support a broader implementation of CPET to provide insight into the role of CRF and its underlying determinants of aging and age-related conditions.

Fatigue and perceived energy in a sample of older adults over 10 years: A resting state functional connectivity study of neural correlates.

PURPOSE: Declining energy and increasing fatigue, common in older age, predict neurodegenerative conditions, but their neural substrates are not known. We examined brain resting state connectivity in relation to declining self-reported energy levels (SEL) and occurrence of fatigue over time. METHODS: We examined resting-state functional MRI in 272 community dwelling older adults participating in the Health Aging and Body Composition Study (mean age 83 years; 57.4 % female; 40.8 % Black) with measures of fatigue and SEL collected at regular intervals over the prior ten years. Functional connectivity (FC) between cortex and striatum was examined separately for sensorimotor, executive, and limbic functional subregions. Logistic regression tested the association of FC in each network with prior fatigue state (reporting fatigue at least once or never reporting fatigue), and with SEL decline (divided into stable or declining SEL groups) and adjusted for demographic, physical function, mood, cognition, and comorbidities. RESULTS: Higher cortico-striatal FC in the right limbic network was associated with lower odds of reporting fatigue (better) at least once during the study period (adjusted odds ratio [95 % confidence interval], p-value: (0.747 [0.582, 0.955], 0.020), independent of SEL. Higher cortico-striatal FC in the right executive network was associated with higher odds of declining SEL (worse) during the study period (adjusted odds ratio [95 % confidence interval], p-value: (1.31 [1.01, 1.69], 0.041), independent of fatigue. Associations with other networks were not significant. CONCLUSIONS: In this cohort of older adults, the cortico-striatal functional connectivity of declining SEL appears distinct from that underlying fatigue. Studies to further assess the neural correlates of energy and fatigue, and their independent contribution to neurodegenerative conditions are warranted.

Associations of accelerometry-measured and self-reported physical activity and sedentary behavior with skeletal muscle energetics: The Study of Muscle, Mobility and Aging (SOMMA).

BACKGROUND: Skeletal muscle energetics decline with age, and physical activity (PA) has been shown to offset these declines in older adults. Yet, many studies reporting these effects were based on self-reported PA or structured exercise interventions. Therefore, we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior (SB) with skeletal muscle energetics and explored the extent to which PA and sedentary behavior would attenuate the associations of age with muscle energetics. METHODS: As part of the Study of Muscle, Mobility and Aging, enrolled older adults (n = 879), 810 (age = 76 ± 5 years old, mean ± SD; 58% women) had maximal muscle oxidative capacity measured ex vivo via high-resolution respirometry of permeabilized myofibers (maximal oxidative phosphorylation (maxOXPHOS)) and in vivo by 31phosphorus magnetic resonance spectroscopy (maximal adenosine triphosphate (ATPmax)). Accelerometry-measured sedentary behavior, light activity, and moderate-to-vigorous PA (MVPA) were assessed using a wrist-worn ActiGraph GT9X over 7 days. Self-reported sedentary behavior, MVPA, and all PA were assessed with the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire. Linear regression models with progressive covariate adjustments evaluated the associations of sedentary behavior and PA with muscle energetics, as well as the attenuation of the age/muscle energetics association by MVPA and sedentary behavior. As a sensitivity analysis, we also examined activPAL-measured daily step count and time spent in sedentary behavior and their associations with muscle energetics. RESULTS: Every 30 min/day more of ActiGraph-measured MVPA was associated with 0.65 pmol/(s × mg) higher maxOXPHOS and 0.012 mM/s higher ATPmax after adjusting for age, site/technician, and sex (p < 0.05). Light activity was not associated with maxOXPHOS or ATPmax. Meanwhile, every 30 min/day spent in ActiGraph-measured sedentary behavior was associated with 0.39 pmol/s × mg lower maxOXPHOS and 0.006 mM/s lower ATPmax (p < 0.05). Only associations with ATPmax held after further adjusting for socioeconomic status, body mass index, lifestyle factors, and multimorbidity. CHAMPS MVPA and all PA yielded similar associations with maxOXPHOS and ATPmax (p < 0.05), but sedentary behavior did not. Higher activPAL step count was associated with higher maxOXHPOS and ATPmax (p < 0.05), but time spent in sedentary behavior was not. Additionally, age was significantly associated with muscle energetics for men only (p < 0.05); adjusting for time spent in ActiGraph-measured MVPA attenuated the age association with ATPmax by 58% in men. CONCLUSION: More time spent in accelerometry-measured or self-reported daily PA, especially MVPA, was associated with higher skeletal muscle energetics. Interventions aimed specifically at increasing higher intensity activity might offer potential therapeutic interventions to slow age-related decline in muscle energetics. Our work also emphasizes the importance of taking PA into consideration when evaluating associations related to skeletal muscle energetics.

Age Is Associated With Dampened Circadian Patterns of Rest and Activity: The Study of Muscle, Mobility, and Aging (SOMMA).

BACKGROUND: The effects of aging on circadian patterns of behavior are insufficiently described. To address this, we characterized age-specific features of rest-activity rhythms (RAR) in community-dwelling older adults both overall, and in relation, to sociodemographic characteristics. METHODS: We examined cross-sectional associations between RAR and age, sex, race, education, multimorbidity burden, financial, work, martial, health, and smoking status using assessments of older adults with wrist-worn free-living actigraphy data (N = 820, age = 76.4 years, 58.2% women) participating in the Study of Muscle, Mobility, and Aging (SOMMA). RAR parameters were determined by mapping an extension to the traditional cosine curve to activity data. Functional principal component analysis determined variables accounting for variance. RESULTS: Age was associated with several metrics of dampened RAR; women had stronger and more robust RAR versus men (all p < .05). Total activity (56%) and time of activity (20%) accounted for most of the RAR variance. Compared to the latest decile of acrophase, those in the earliest decile had higher average amplitude (p < .001). Compared to the latest decile of acrophase, those in the earliest and midrange categories had more total activity (p = .02). Being in a married-like relationship and a more stable financial situation were associated with stronger rhythms; higher education was associated with less rhythm strength (all p < .05). CONCLUSIONS: Older age was associated with dampened circadian behavior; behaviors were sexually dimorphic. Some sociodemographic characteristics were associated with circadian behavior. We identified a behavioral phenotype characterized by early time of day of peak activity, high rhythmic amplitude, and more total activity.

Associations of depression and perceived physical fatigability with white matter integrity in older adults.

BACKGROUNDS: Fatigability is prevalent in older adults. However, it is often associated with depressed mood. We aim to investigate these two psychobehavioral constructs by examining their underpinning of white matter structures in the brain and their associations with different medical conditions. METHODS: Twenty-seven older adults with late-life depression (LLD) and 34 cognitively normal controls (CN) underwent multi-shell diffusion MRI. Fatigability was measured with the Pittsburgh Fatigability Scale. We examined white matter integrity by measuring the quantitative anisotropy (QA), a fiber tracking parameter with better accuracy than the traditional imaging technique. RESULTS: We found those with LLD had lower QA in the 2nd branch of the left superior longitudinal fasciculus (SLF-II), and those with more physical fatigability had lower QA in more widespread brain regions. In tracts associated with more physical fatigability, the lower QA in left acoustic radiation and left superior thalamic radiation correlated with higher blood glucose (r = - 0.46 and - 0.49). In tracts associated with depression, lower QA in left SLF-II correlated with higher bilirubin level (r = - 0.58). DISCUSSION: Depression and fatigability were associated with various white matter integrity changes, which correlated with biochemistry biomarkers all related to inflammation.

Recruitment and baseline data of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study: A randomized trial of a hearing loss intervention for reducing cognitive decline.

INTRODUCTION: Hearing loss is highly prevalent among older adults and independently associated with cognitive decline. The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study is a multicenter randomized control trial (partially nested within the infrastructure of an observational cohort study, the Atherosclerosis Risk in Communities [ARIC] study) to determine the efficacy of best-practice hearing treatment to reduce cognitive decline over 3 years. The goal of this paper is to describe the recruitment process and baseline results. METHODS: Multiple strategies were used to recruit community-dwelling 70-84-year-old participants with adult-onset hearing loss who were free of substantial cognitive impairment from the parent ARIC study and de novo from the surrounding communities into the trial. Participants completed telephone screening, an in-person hearing, vision, and cognitive screening, and a comprehensive hearing assessment to determine eligibility. RESULTS: Over a 24-month period, 3004 telephone screenings resulted in 2344 in-person hearing, vision, and cognition screenings and 1294 comprehensive hearing screenings. Among 1102 eligible, 977 were randomized into the trial (median age = 76.4 years; 53.5% female; 87.8% White; 53.3% held a Bachelor's degree or higher). Participants recruited through the ARIC study were recruited much earlier and were less likely to report hearing loss interfered with their quality of life relative to participants recruited de novo from the community. Minor differences in baseline hearing or health characteristics were found by recruitment route (i.e., ARIC study or de novo) and by study site. DISCUSSION: The ACHIEVE study successfully completed enrollment over 2 years that met originally projected rates of recruitment. Substantial operational and scientific efficiencies during study startup were achieved through embedding this trial within the infrastructure of a longstanding and well-established observational study. Highlights: The ACHIEVE study tests the effect of hearing intervention on cognitive decline.The study is partially nested within an existing cohort study.Over 2 years, 977 participants recruited and enrolled.Eligibility assessed by telephone and in-person for hearing, vision, and cognitive screening.The ACHIEVE study findings will have significant public health implications.

Energetics and clinical factors for the time required to walk 400 m: The Study of Muscle, Mobility and Aging (SOMMA).

BACKGROUND: Walking slows with aging often leading to mobility disability. Mitochondrial energetics has been found to be associated with gait speed over short distances. Additionally, walking is a complex activity but few clinical factors that may be associated with walk time have been studied. METHODS: We examined 879 participants ≥70 years and measured the time to walk 400 m. We tested the hypothesis that decreased mitochondrial energetics by respirometry in muscle biopsies and magnetic resonance spectroscopy in the thigh and is associated with longer time to walk 400 m. We also used cardiopulmonary exercise testing to assess the energetic costs of walking: maximum oxygen consumption (VO2peak) and energy cost-capacity (the ratio of VO2, at a slow speed to VO2peak). In addition, we tested the hypothesis that selected clinical factors would also be associated with 400-m walk time. RESULTS: Lower Max OXPHOS was associated with longer walk time, and the association was explained by the energetic costs of walking, leg power, and weight. Additionally, a multivariate model revealed that longer walk time was also significantly associated with lower VO2peak, greater cost-capacity ratio, weaker leg power, heavier weight, hip and knee stiffness, peripheral neuropathy, greater perceived exertion while walking slowly, greater physical fatigability, less moderate-to-vigorous exercise, less sedentary time, and anemia. Significant associations between age, sex, muscle mass, and peripheral artery disease with 400-m walk time were explained by other clinical and physiologic factors. CONCLUSIONS: Lower mitochondrial energetics is associated with needing more time to walk 400 m. This supports the value of developing interventions to improve mitochondrial energetics. Additionally, doing more moderate-to-vigorous exercise, increasing leg power, reducing weight, treating hip and knee stiffness, and screening for and treating anemia may reduce the time required to walk 400 m and reduce the risk of mobility disability.

The Association of Skeletal Muscle Energetics With Recurrent Falls in Older Adults Within the Study of Muscle, Mobility and Aging.

BACKGROUND: Falls in the older population are a major public health concern. While many physiological and environmental factors have been associated with fall risk, muscle mitochondrial energetics has not yet been investigated. METHODS: In this analysis, 835 Study of Muscle, Mobility and Aging (SOMMA) participants aged 70-94 were surveyed for number of falls (total), recurrent falls (2+), and fall-related injuries over the past 12 months at baseline and again after 1 year. Skeletal muscle energetics were assessed at baseline in vivo using 31P Magnetic Resonance Spectroscopy for the maximal rate of adenosine triphosphate recovery (ATPmax) after an acute bout of exercise, and ex vivo by High-Resolution Respirometry for the maximal rate of complex I and II supported oxygen consumption (MaxOXPHOS) in permeabilized muscle fibers from the vastus lateralis. RESULTS: At least 1 fall was reported in 28.7% of SOMMA participants in the first year of the study, with 12% of older adults reporting recurrent falls (2+). Individuals who experienced recurrent falls had a slower 400-m walk gait speed (1.0 ± 0.2 vs 1.1 ± 0.2, p < .001), reported fewer alcoholic drinks per week in the past year (2.4 ± 4.3 vs 2.8 ± 4.4, p = .054), and took a significantly greater number of medication in the 30 days before their baseline visit (5.6 ± 4.4 vs 4.2 ± 3.4, p < .05). A history of falls was reported in 63% of individuals who experienced recurrent falls in the first year of the study compared to 22.8% who experienced 1 or fewer falls. MaxOXPHOS was significantly lower in those who reported recurrent falls (p = .008) compared to those with 1 or fewer falls, but there was no significant difference in ATPmax (p = .369). Neither muscle energetics measure was significantly associated with total number of falls or injurious falls, but recurrent falls were significantly higher with lower MaxOXPHOS (risk ratio = 1.33, 95% confidence interval = 1.02-1.73, p = .033). However, covariates accounted for the increased risk. CONCLUSIONS: Mitochondrial energetics were largely unrelated to fall risk in older adults when accounting for variables, suggesting that the complex etiology of falls may not be related to a single "hallmark of aging" biological pathway.

Description of the Baseline Audiologic Characteristics of the Participants Enrolled in the Aging and Cognitive Health Evaluation in Elders Study.

PURPOSE: The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study is a randomized clinical trial designed to determine the effects of a best-practice hearing intervention versus a successful aging health education control intervention on cognitive decline among community-dwelling older adults with untreated mild-to-moderate hearing loss. We describe the baseline audiologic characteristics of the ACHIEVE participants. METHOD: Participants aged 70-84 years (N = 977; Mage = 76.8) were enrolled at four U.S. sites through two recruitment routes: (a) an ongoing longitudinal study and (b) de novo through the community. Participants underwent diagnostic evaluation including otoscopy, tympanometry, pure-tone and speech audiometry, speech-in-noise testing, and provided self-reported hearing abilities. Baseline characteristics are reported as frequencies (percentages) for categorical variables or medians (interquartiles, Q1-Q3) for continuous variables. Between-groups comparisons were conducted using chi-square tests for categorical variables or Kruskal-Wallis test for continuous variables. Spearman correlations assessed relationships between measured hearing function and self-reported hearing handicap. RESULTS: The median four-frequency pure-tone average of the better ear was 39 dB HL, and the median speech-in-noise performance was a 6-dB SNR loss, indicating mild speech-in-noise difficulty. No clinically meaningful differences were found across sites. Significant differences in subjective measures were found for recruitment route. Expected correlations between hearing measurements and self-reported handicap were found. CONCLUSIONS: The extensive baseline audiologic characteristics reported here will inform future analyses examining associations between hearing loss and cognitive decline. The final ACHIEVE data set will be publicly available for use among the scientific community. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24756948.

The association between frailty and perceived physical and mental fatigability: The Long Life Family Study.

BACKGROUND: Higher levels of frailty, quantified by a frailty index (FI), may be linked to fatigue severity as tasks become more physically and mentally demanding. Fatigue, a component of frailty research, has been ambiguous and inconsistent in its operationalization. Fatigability-the quantification of vulnerability to fatigue in relation to specific intensity and duration of activities-offers a more sensitive and standardized approach, though the association between frailty and fatigability has not been assessed. METHODS: Using cross-sectional data from the Long Life Family Study at Visit 2 (2014-2017; N = 2524; mean age ± standard deviation (SD) 71.4 ± 11.2 years; 55% women; 99% White), we examined associations between an 83-item FI after excluding fatigue items (ratio of number of health problems reported (numerator) out of the total assessed (denominator); higher ratio = greater frailty) and perceived physical and mental fatigability using the Pittsburgh Fatigability Scale (PFS) (range 0-50; higher scores = greater fatigability). RESULTS: Participants had mean ± standard deviation FI (0.08 ± 0.06; observed range: 0.0-0.43), PFS Physical (13.7 ± 9.6; 39.5% more severe, ≥15), and PFS Mental (7.9 ± 8.9; 22.8% more severe, ≥13). The prevalence of more severe physical and mental fatigability was higher across FI quartiles. In mixed effects models accounting for family structure, a clinically meaningful 3%-higher FI was associated with 1.9 points higher PFS Physical score (95% confidence interval (CI) 1.7-2.1) and 1.7 points higher PFS Mental score (95% CI 1.5-1.9) after adjusting for covariates. CONCLUSIONS: Frailty was associated with perceived physical and mental fatigability severity. Understanding this association may support the development of interventions to mitigate the risks associated with greater frailty and perceived fatigability. Including measurements of perceived fatigability, in lieu of fatigue, in frailty indices has the potential to alleviate the inconsistencies and ambiguity surrounding the operationalization of fatigue and provide a more precise and sensitive measurement of frailty.

Loneliness and Social Network Characteristics Among Older Adults With Hearing Loss in the ACHIEVE Study.

BACKGROUND: Hearing loss is linked to loneliness and social isolation, but evidence is typically based on self-reported hearing. This study quantifies the associations of objective and subjective hearing loss with loneliness and social network characteristics among older adults with untreated hearing loss. METHODS: This study uses baseline data (N = 933) from the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study. Hearing loss was quantified by the better ear, speech-frequency pure tone average (PTA), Quick Speech-in-Noise test, and hearing-related quality of life. Outcomes were validated measures of loneliness and social network characteristics. Associations were assessed by Poisson, negative binomial, and linear regression adjusted for demographic, health, and study design characteristics. RESULTS: Participants were mean of 76.8 (4.0) years, 54.0% female, and 87.6% White. Prevalence of loneliness was 38%. Worse PTA was associated with a 19% greater prevalence of moderate or greater loneliness (prevalence ration [PR]: 1.19.95% CI: 1.06, 1.33). Better speech-in-noise recognition was associated with greater social network characteristics (eg, larger social network size [IRR: 1.04, 95% CI: 1.00, 1.07]). Worse hearing-related quality of life was associated with a 29% greater prevalence of moderate or greater loneliness (PR: 1.29, 95% CI: 1.19, 1.39) and worse social network characteristics (eg, more constricted social network size [IRR: 0.96, 95% CI: 0.91, 1.00]). CONCLUSIONS: Results suggest the importance of multiple dimensions of hearing to loneliness and social connectedness. Hearing-related quality of life may be a potentially useful, easily administered clinical tool for identifying older adults with hearing loss associated with greater loneliness and social isolation.

Vigor to Frailty As a Continuum-A New Approach in the Study of Muscle, Mobility, and Aging Cohort.

BACKGROUND: Frailty can occur in older adults without disability or multimorbidity. Current methods focus on the most frail, but poorly discriminate among those "not frail." METHODS: The Study of Muscle, Mobility, and Aging (SOMMA) included 879 adults aged 70 years and older without mobility disability. We operationalized frailty domains using: peak oxygen consumption (endurance), digit symbol substitution test (speed), leg power (strength), perceived fatigability, D3 creatine dilution (sarcopenia), and accelerometry (sedentary behavior) to construct a frailty score of 0-12 summing tertiles (0-2) of each component. We used linear or logistic regression with and without adjustment for confounders to examine associations with age, reported, and performance function. RESULTS: The SOMMA frailty score distribution was broad and strongly associated with age (r = 0.33, p < .0001). Each point was associated with a 30%-50% higher odds of having reported difficulty with activities of daily living or mobility. After grouping the total score (0-3, 4-7, and 8-12) those in the highest group were 9-31 times more likely to have functional limitation, and at least 8 times more likely to have poorer function after full adjustment. Higher scores identified those less likely to report ease of walking or higher physical activity. Peak oxygen consumption, leg power, fatigability, and digit symbol score contributed most to these associations. CONCLUSIONS: The SOMMA frailty score characterizes frailty as a continuum from frail to vigorous with assessments that are amenable to change. Associations with age and function suggest utility for distinguishing a wide range of vigor and vulnerability in relatively well-functioning older adults.

Depression and Health-Related Quality of Life Among Older Adults With Hearing Loss in the ACHIEVE Study.

Hearing loss is associated with cognitive/physical health; less is known about mental health. We investigated associations between hearing loss severity, depression, and health-related quality of life among older adults with unaided hearing loss. Data (N = 948) were from the Aging and Cognitive Health Evaluation in Elders Study. Hearing was measured by pure-tone average (PTA), Quick Speech-in-Noise (QuickSIN) test, and the Hearing Handicap Inventory for the Elderly (HHIE-S). Outcomes were validated measures of depression and health-related quality of life. Associations were assessed by negative binomial regression. More severe hearing loss was associated with worse physical health-related quality of life (ratio: .98, 95% CI: .96, 1.00). Better QuickSIN was associated with higher mental health-related quality of life (1.01 [1.00, 1.02]). Worse HHIE-S was associated with depression (1.24 [1.16, 1.33]) and worse mental (.97 [.96, .98]) and physical (.95 [ .93, .96]) health-related quality of life. Further work will test effects of hearing intervention on mental health.

Usual-paced 400 m long distance corridor walk estimates cardiorespiratory fitness among older adults: The Study of Muscle, Mobility and Aging.

BACKGROUND: Cardiopulmonary exercise testing (CPET), the gold-standard method to quantify cardiorespiratory fitness (CRF), is not always feasible due to cost, access, and burden. The usual-paced 400 m long distance corridor walk (LDCW), a measure of mobility among older adults, may provide an alternate method to assess CRF. The purpose of this study was to develop and validate an estimating equation to estimate VO2 peak from average 400 m walking speed (WS) among participants in the Study of Muscle, Mobility and Aging (SOMMA). METHODS: At baseline, women (58%) and men age 70 years and older enrolled in SOMMA (N = 820, 76.2 ± 4.9 years, 86% Non-Hispanic White) completed a 400 m LDCW (400 m WS = 400 m/completion time in seconds) and symptom-limited maximal CPET (Modified Balke Protocol). VO2 peak (mL/kg/min) was considered the highest 30-second average oxygen consumption during CPET. Other covariates included: age, sex, race, physical activity (7-day wrist-worn accelerometer), physical function (Short Physical Performance Battery, range 0-12), perceived physical fatigability (Pittsburgh Fatigability Scale, range 0-50), and Borg Rating of Perceived Exertion (RPE, range 6-20) at completion of the 400 m LDCW. Stepwise linear regression was used. Internal validation was completed using data-splitting method (70%; 30%). RESULTS: Mean VO2 peak was 20.2 ± 4.8 mL/kg/min and mean 400 m WS was 1.06 ± 0.2 m/s. Each 0.05 m/s increment in 400 m WS was associated with a 0.40 mL/kg/min higher VO2 peak after covariate adjustment. An estimating equation including 400 m WS, age, sex, race, and RPE was developed. Internal validation showed low overall bias (-0.26) and strong correlation (r = 0.71) between predicted and measured VO2 peak values. Bland-Altman plot and regression analyses indicated predicted VO2 peak was an acceptable alternative, despite mean underestimation of 4.53 mL/kg/min among the highly fit. CONCLUSIONS: Usual-paced 400 m LDCW strongly correlates with direct measures of CRF during CPET in older adults with lower fitness and can be used to test both fitness and function.

Measuring and Understanding the Health Impact of Greater Fatigability in Older Adults: A Call to Action and Opportunities.

Different from fatigue, an instantaneous state of tiredness, weakness and lack of energy, fatigability is a trait that contextualizes whole-body fatigue to the level of activity (i.e., intensity and duration) with which the fatigue is associated. Fatigability can be perceived or performance-related. Measuring fatigability improves upon traditional fatigue measures by accounting for self-pacing as older adults likely slow down or limit their daily activity to maintain fatigue in a tolerable range. Anchoring fatigue to activities/tasks improves sensitivity and allows for meaningful comparisons across individuals/between studies, as well as evaluating change over time and treatment effects. Two well-validated approaches are utilized to measure perceived fatigability: 1) a 5-minute slow-paced (1.5 mph/0.67 m/s, 0% grade) treadmill walk immediately followed by Borg rating of perceived exertion; and 2) a self-administered 10-item questionnaire, Pittsburgh Fatigability Scale, with both physical and mental subscales. Many walking-based performance fatigability measures are based on certain lap time or distance, while the Pittsburgh Performance Fatigability Index uses raw accelerometry data to quantify percent of cadence decline over the entire long distance walking tasks. Perceived fatigability prevalence ranges from 20-90% in older adults varying by assessment tool, and is higher with advancing age and in women compared to men. Fatigability is associated with physical and cognitive function, fall risk, mobility decline, and mortality. Unfortunately, the available research lacks representativeness in terms of racial and ethnic diversity. The time is now to incorporate our established sensitive and validated fatigability measures into global research and clinical practice to better understand mechanistic underpinnings and reveal intervention effects to reduce the burden and lessen the consequences of greater fatigability worldwide.

The association of skeletal muscle energetics with recurrent falls in older adults within the Study of Muscle, Mobility and Aging (SOMMA).

Background: Falls in the older population are a major public health concern. While many physiological and environmental factors have been associated with fall risk, muscle mitochondrial energetics has not yet been investigated. Methods: In this analysis, 835 Study of Muscle, Mobility and Aging (SOMMA) participants aged 70-94 were surveyed for recurrent falls (2+) after one year. Skeletal muscle energetics were assessed at baseline in vivo using 31 P Magnetic Resonance Spectroscopy (MRS) (ATPmax) and ex vivo by High Resolution Respirometry (HRR) of permeabilized muscle fibers from the vastus lateralis (MaxOXPHOS). Results: SOMMA participants who reported recurrent falls (12%) had a slower 400m walk gait speed compared to those with 0-1 falls (1.0 +/-0.2 vs. 1.1 +/-0.2, p<.001) and took a greater number of medication in the 30 days before their baseline visit (5.6 +/-4.4 vs. 4.2 +/-3.4, p<0.05). MaxOXPHOS was significantly lower in those who reported recurrent falls (p=0.008) compared to those with one or fewer falls, but there was no significant difference in ATPmax (p=0.369). Neither muscle energetics measure was significantly associated with total number of falls or injurious falls, but recurrent falls were significantly higher with lower MaxOXPHOS (RR=1.33, 95% CI= 1.02-1.73, p=0.033). However, covariates accounted for the increased risk. Conclusions: Ex vivo maximal muscle mitochondrial energetics were lower in older adults who experienced recurrent falls, but covariates accounted for its association with recurrent fall risk, suggesting this "hallmark of aging" may not be directly implicated in the complex etiology of falls.

Age is Associated with Dampened Circadian Patterns of Rest and Activity: The Study of Muscle, Mobility and Aging (SOMMA).

Background: Aging is associated with declines in circadian functions. The effects of aging on circadian patterns of behavior are insufficiently described. We characterized age-specific features of rest-activity rhythms (RAR) in community dwelling older adults, both overall, and in relation, to sociodemographic characteristics. Methods: We analyzed baseline assessments of older adults with wrist-worn free-living wrist-worn actigraphy data (N=820, Age=76.4 yrs, 58.2% women) participating in the Study of Muscle, Mobility and Aging (SOMMA). We applied an extension to the traditional cosine curve to map RAR to activity data, calculating the parameters: rhythmic strength (amplitude); robustness (pseudo-F statistic); and timing of peak activity (acrophase). We also used function principal component analysis to determine 4 components describing underlying patterns of activity accounting for RAR variance. Linear models were used to examine associations between RAR and sociodemographic variables. Results: Age was associated with several metrics of dampened RAR; women had stronger and more robust RAR metrics vs. men (all P < 0.05). Total activity (56%) and time of activity (20%) accounted for most the RAR variance. Compared to the latest decile of acrophase, those in the earliest decile had higher average amplitude (P <0.001). Compared to the latest decile of acrophase, those is the earliest and midrange categories had more total activity (P=0.02). RAR was associated with some sociodemographic variables. Conclusions: Older age was associated with dampened circadian behavior; and behaviors were sexually dimorphic. We identified a behavioral phenotype characterized by early time-of-day of peak activity, high rhythmic amplitude, and more total activity.

Associations of Objective and Self-Reported Physical Activity and Sedentary Behavior with Skeletal Muscle Energetics: The Study of Muscle, Mobility and Aging (SOMMA).

Background: Skeletal muscle energetics decline with age, and physical activity (PA) has been shown to counteract these declines in older adults. Yet, many studies were based on self-reported PA or structured exercise interventions. We examined the associations of objective daily PA and sedentary behavior (SB) with skeletal muscle energetics and also compared with self-reported PA and SB. We also explored the extent to which PA would attenuate the associations of age with muscle energetics. Methods: Among the Study of Muscle, Mobility and Aging (SOMMA) enrolled older adults, 810 (mean age=76±5, 58% women) had maximal muscle oxidative capacity measured ex vivo via high-resolution respirometry of permeabilized myofibers (maxOXPHOS) and in vivo by 31 Phosphorus magnetic resonance spectroscopy (ATP max ). Objective PA was measured using the wrist-worn ActiGraph GT9X over 7-days to capture sedentary behavior (SB), light, and moderate-to-vigorous PA (MVPA). Self-reported SB, MVPA, and all exercise-related PA were assessed with The Community Healthy Activities Model Program for Seniors questionnaire. Linear regression models with progressive covariate adjustments evaluated the associations between SB, PA and muscle energetics, and the attenuation of the age / muscle energetic association by PA. Results: Every 30 minutes more objective MVPA was associated with 0.65 pmol/s*mg higher maxOXPHOS and 0.012 mM/sec higher ATP max , after adjustment for age, site/technician and sex. More time spent in objective light+MVPA was significantly associated with higher ATP max , but not maxOXPHOS. In contrast, every 30 minutes spent in objective SB was associated with 0.43 pmol/s*mg lower maxOXPHOS and 0.004 mM/sec lower ATP max . Only associations with ATP max held after further adjusting for socioeconomic status, body mass index, lifestyle factors and multimorbidities. Self-reported MVPA and all exercise-related activities, but not SB, yielded similar associations with maxOXPHOS and ATP max . Lastly, age was only significantly associated with muscle energetics in men. Adjusting for objective time spent in MVPA attenuated the age association with ATP max by nearly 60% in men. Conclusion: More time spent in daily PA, especially MVPA, were associated with higher muscle energetics. Interventions that increase higher intensity activity might offer potential therapeutic interventions to slow the age-related decline in muscle energetics. Our work also emphasizes the importance of taking PA into consideration when evaluating associations related to skeletal muscle energetics.