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Background: Cardiovascular disease is associated with higher incidence of frailty. However, the nature of the mechanisms underlying this association remains unclear. The purpose of this study is to identify cardiovascular phenotypes most associated with physical frailty and functional performance in the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods: As part of the MESA study, 3 045 participants underwent cardiovascular magnetic resonance and computed tomography between 2010 and 2012. Of these, 1 743 completed a Six-Minute Walk test (6MWT) and questionnaires (follow-up exam: 2016-2018) which were used to generate a binary combined frail/prefrail versus robust score according to a modified FRAIL Scale (self-report questionnaire). Multivariable logistic (binary frail outcome) or linear (6MWT) regression assessed the association between frailty and cardiovascular structure and function, aortic stiffness, coronary artery calcium, and myocardial fibrosis (ECV, extracellular volume fraction)., Results: Participants were 66 ± 8 years, 52% female at the time of imaging, and 29.4% were classified as frail or prefrail. Older age and female gender were associated with greater odds of being in the frail/prefrail group. Concentric left ventricular remodeling (odds ratio [OR] 1.89, p = .008; Coef. -52.9, p < .001), increased ECV (OR 1.10, p = .002; Coef. -4.0, p = .001), and worsening left atrial strain rate at early diastole (OR 1.56, p ≤ .001; Coef. -22.75, p = .027) were found to be associated with a greater likelihood of being in a frail state and lower 6MWT distance (m). All associations with 6MWT performance were attenuated with adjustments for risk factors whereas ECV and LA strain rate remained independently associated with frailty., Conclusions: These findings suggest a significant overlap in pathways associated with subclinical cardiac dysfunction, cardiovascular fibrosis, and physical frailty., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The development of disability related to activities of daily living (ADL) is of great concern in the aging population, particularly for Hispanic and Non-Hispanic (NH) Black older adults, where disability prevalence is greater compared to NH Whites. ADL-disability is typically measured across many functional tasks without differentiating upper- versus lower-limb limitations, hindering our understanding of disability burden. Despite the importance of the upper limbs for completing ADL and known age-related declines in function, racial/ethnic differences in upper limb function remain largely unknown., Methods: We identified 4 292 NH White, NH Black, and Mexican American older adults (≥65) from the 2011-2018 waves of the National Health and Nutrition Examination Survey (NHANES). We classified participants as having a limitation based on their ability to complete 5 upper-limb tasks (preparing meals, eating, dressing, reaching overhead, and grasping small objects) and compared limitation rates across racial/ethnic groups., Results: Compared to NH Whites, NH Black older adults had significantly greater odds of reporting difficulties preparing meals (odds ratio [OR]: 1.36, 95% confidence interval [95% CI]: 1.01, 1.86) and dressing (OR: 1.55, 95% CI: 1.19, 2.02), while Mexican Americans had greater difficulty preparing meals (OR: 1.70, 95% CI: 1.12, 2.58), dressing (OR: 1.63, 95% CI: 1.12, 2.36), and grasping small objects (OR: 1.48, 95% CI: 1.06, 2.07)., Conclusions: Our results demonstrate differences in self-reported upper limb ADL-disability across racial/ethnic groups, particularly for Mexican American older adults. Such findings underscore the need for routine monitoring of upper limb function throughout adulthood to identify limitations and target therapeutic interventions before independence is compromised., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Appropriate conceptualization and measurement of disability are critical for population-focused resource allocation and policy development. Self-reported and performance-based measures of functioning have been used to represent disability. Variation in environmental context or self-perception of ability may influence self-reports; however, performance-based measures that attempt to control environmental context may not accurately capture real-world aspects of functioning. This study examined the agreement between self-report and performance-based measures of functioning within 4 domains among older adults., Methods: Cross-sectional data from the 2021 National Health and Aging Trends Study was used. Self-reported and performance-based measures of functioning were assessed for vision, hearing, mobility, and memory domains. We examined the diagnostic characteristics of performance-based versus self-reported measures using sensitivity, specificity, and receiver operating characteristics curves. Differences in the agreement of these measures across sociodemographic groups were investigated using logistic regression., Results: Among 2 442 respondents 71 years and older (mean 78.5 ± 5.3, 56% female participants), performance measures of hearing and mobility had high sensitivity (89% and 91%, respectively) and low/moderate specificity (36% and 63%, respectively). The sensitivity and specificity of vision measures were 71%. Memory measures had high specificity (89%) and low sensitivity (28%). Performance-based discrimination ranged from 0.59 (memory) to 0.78 (mobility). Agreement varied across sociodemographic factors., Conclusions: Performance measures diverge from self-reported functioning among older adults. Discordance may reveal opportunities for environmental intervention where participants' performance does not capture the full extent of barriers in their daily lives. Additional research is needed to investigate individual and environmental factors which could explain the observed differences., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Physical activity and exercise training exert multiple and varied beneficial effects on a wide array of human tissues, making them therapeutic modalities that can prevent and treat age-related decline in physical function. The Molecular Transducers of Physical Activity Consortium is currently working to elucidate the molecular mechanisms underlying how physical activity improves and preserves health. Exercise training, especially when task specific, is an effective intervention for improving skeletal muscle performance and physical function in everyday activities. As seen elsewhere in this supplement, its adjunctive use with pro-myogenic pharmaceuticals may prove to be synergistic in effect. Behavioral strategies aiming to promote exercise participation and sustain adherence are being considered as additional adjuncts to further improve physical function in comprehensive, multicomponent interventions. One application of this combined strategy may be to target multimodal pro-myogenic therapies in prehabilitation to optimize physical preoperative health to enhance functional recovery postsurgery. We summarize here recent progress on biological mechanisms of exercise training, behavioral approaches to exercise participation, and the role task-specific exercise plays in synergy with pharmacologic therapies with a particular focus on older adults. Physical activity and exercise training in multiple settings should serve as the baseline standard of care around which other therapeutic interventions should be considered when the goal is restoring or increasing physical function., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Physical performance and fatigue can limit mobility within the larger environment (life-space mobility). It is unknown whether perceived fatigability, self-reported fatigue anchored to activity intensity and duration, is independently associated with life-space., Methods: We assessed this cross-sectionally in Visit 4 (2014-2016) of the Osteoporotic Fractures in Men Study (MrOS; N = 1 672, Age: Mean = 84.2 ± 4.0 years). The Pittsburgh Fatigability Scale (PFS, range: 0-50; higher = greater fatigability) measured physical (Mean = 16.1 ± 9.4) and mental fatigability (Mean = 7.5 ± 7.9). Life Space Assessment scores incorporated level, frequency, and assistance used for life-space mobility (range: 0-120, higher = greater life-space mobility; life-space constriction: inability to leave neighborhood without assistance). Separate multiple linear and logistic regressions for physical and mental fatigability were sequentially adjusted for demographic, health/lifestyle, and performance measures., Results: The mean life-space mobility score was 84.6 ± 21.8, and 18% (n = 296) of men had life-space constriction. Higher physical and mental fatigability were both associated with lower life-space mobility in models adjusted for health and lifestyle factors (Physical PFS: B = -2.37, 95% confidence interval [CI]: [-3.39, -1.35]; Mental PFS: B = -1.79, 95% CI: [-2.73, -0.84]). Men with higher fatigability also had increased risk of life-space constriction (Physical PFS: OR = 1.59, 95% CI: [1.32, 1.92]; Mental PFS: OR = 1.25, 95% CI: [1.08, 1.46]). Associations were larger in magnitude for physical versus mental fatigability. Adjusting for physical performance measures more strongly attenuated associations for physical compared to mental fatigability., Conclusions: Fatigability is linked with real-world mobility in older men, independent of their physical health. This association may be driven by separate physical and cognitive mechanisms worth examining further in longitudinal studies., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The ability to capture people's movement throughout their home is a powerful approach to inform spatiotemporal patterns of routines associated with cognitive impairment. The study estimated indoor room activities over 24 hours and investigated relationships between diurnal activity patterns and mild cognitive impairment (MCI)., Methods: One hundred and sixty-one older adults (26 with MCI) living alone (age = 78.9 ± 9.2) were included from 2 study cohorts-the Oregon Center for Aging & Technology and the Minority Aging Research Study. Indoor room activities were measured by the number of trips made to rooms (bathroom, bedroom, kitchen, living room). Trips made to rooms (transitions) were detected using passive infrared motion sensors fixed on the walls for a month. Latent trajectory models were used to identify distinct diurnal patterns of room activities and characteristics associated with each trajectory., Results: Latent trajectory models identified 2 diurnal patterns of bathroom usage (high and low usage). Participants with MCI were more likely to be in the high bathroom usage group that exhibited more trips to the bathroom than the low-usage group (odds ratio [OR] = 4.1, 95% CI [1.3-13.5], p = .02). For kitchen activity, 2 diurnal patterns were identified (high and low activity). Participants with MCI were more likely to be in the high kitchen activity group that exhibited more transitions to the kitchen throughout the day and night than the low kitchen activity group (OR = 3.2, 95% CI [1.1-9.1], p = .03)., Conclusions: The linkage between bathroom and kitchen activities with MCI may be the result of biological, health, and environmental factors in play. In-home, real-time unobtrusive-sensing offers a novel way of delineating cognitive health with chronologically-ordered movement across indoor locations., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Good sit-to-stand (STS) performance is an important factor in maintaining functional independence. This study investigated whether free-living STS transition volume and intensity, assessed by a thigh-worn accelerometer, is associated with characteristics related to functional independence., Methods: Free-living thigh-worn accelerometry was recorded continuously for 3-7 days in a population-based sample of 75-, 80-, and 85-year-old community-dwelling people (479 participants; women n = 287, men n = 192). The records were used to evaluate the number and intensity (angular velocity of the STS phase) of STS transitions. Associations with short physical performance battery (SPPB), 5-times-sit-to-stand test (5×STS), isometric knee extension force, self-reported fear of falls, and self-reported difficulty in negotiating stairs were also assessed., Results: The number of STS transitions, mean and maximal angular velocity were lower in older age groups (p < .05). All variables were higher in men than in women (p < .001) and were positively associated with SPPB total points, knee extension force (r ranged from 0.18 to 0.39, all p < .001) and negatively associated with 5×STS (r = -0.13 - -0.24, all p < .05), lower extremity functional limitations (p < .01), fear of falls (p < .01), and stair negotiation difficulties (p < .01)., Conclusions: Free-living STS characteristics were related to lower-extremity performance, lower extremity functional limitations, self-reported fear of falls, and stair negotiation difficulties, which can be a sensitive indicator of impending functional decline. Moreover, STS transitions may provide an indicator of adequacy of lower-limb muscle strength among older individuals., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: The ability to grasp and manipulate objects is essential for performing activities of daily living. However, there is limited information regarding age-related behavioral differences in hand sensorimotor function due, in part, to the lack of assessment tools capable of measuring subtle but important differences in hand function. The purpose of this study was to demonstrate performance differences in submaximal force control and tactile pattern recognition in healthy older adults using 2 custom-designed sensorimotor assessment tools., Methods: Sensorimotor function was assessed in 13 healthy older adults (mean age 72.2 ± 5.5 years, range: 65-84 years) and 13 young adults (mean age 20 ± 1.4 years, range: 19-23 years). Clinical assessments included the Montreal Cognitive Assessment (MoCA), monofilament testing, maximum voluntary contraction (MVC), and Grooved Pegboard Test. Sensorimotor assessments included submaximal (5, 20% MVC) grip force step-tracking and tactile pattern recognition tasks., Results: Clinical assessments revealed no or minimal group differences in MVC, monofilament thresholds, and MoCA. However, sensorimotor assessments showed that older adults took longer to discriminate tactile patterns and had poorer accuracy than young adults. Older adults also produced submaximal forces less smoothly than young adults at the 20% force level while greater variability in force maintenance was seen at 5% but not 20% MVC., Conclusions: These results demonstrate the ability to integrate higher-order tactile information and control low grip forces is impaired in older adults despite no differences in grip strength or cognition. These findings underscore the need for more sensitive evaluation methods that focus on sensorimotor ability reflective of daily activities., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Indices quantifying allostatic load (AL) and biological aging (BA) have independently received widespread use in epidemiological literature. However, little attention has been paid to their conceptual and quantitative overlap. By reviewing literature utilizing measures of AL and BA, and conducting comparative analysis, we highlight similarities and differences in biological markers employed and approach toward scale construction. Further, we outline opportunities where both types of indices might be improved by adopting methodological features of the other., Methods: Using data from the National Survey of Midlife Development in the United States (N = 2055, age = 26-86), we constructed 3 AL indices: 1 common literature standard and 2 alternative formulations informed by previous work with measures of BA. The performance of AL indices was juxtaposed against 2 commonly employed BA indices: Klemera-Doubal Method Biological Age and Homeostatic Dysregulation., Results: All indices correlated with chronological age. Participants with higher AL and older BA performed worse on tests of physical and subjective functioning. Further, participants with increased life-course risk exposure exhibited higher AL and BA. Notably, alternative AL formulations tended to exhibit effect sizes equivalent to or larger than those observed for BA measures, and displayed superior mortality prediction., Conclusions: In addition to their conceptual similarity, AL and BA indices also exhibit significant analytical similarity. Further, BA measures are robust to construction using a panel of biomarkers not observed in previous iterations, including carotenoids indexing antioxidant capacity. In turn, AL indices could benefit by adopting the methodological rigor formalized within BA composites, such as applying biomarker down-selection criteria., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Obesity exacerbates age-related effects on body composition and physical and metabolic function. Which exercise mode is most effective in mitigating these deleterious changes in dieting older adults with obesity is unknown., Methods: In a randomized controlled trial, we performed a head-to-head comparison of aerobic (AEX), resistance (REX), or combination (COMB) exercise during matched ~10% weight loss in 160 obese older adults. Prespecified analyses compared 6-month changes in intermuscular adipose tissue (IMAT) and visceral adipose tissue (VAT) assessed using MRI, insulin sensitivity index (ISI) by oral glucose tolerance test, physical function using Modified Physical Performance Test (PPT), VO2peak, gait speed, and knee strength by dynamometry., Results: IMAT and VAT decreased more in COMB than AEX and REX groups (IMAT; -41% vs -28% and -23% and VAT: -36% vs -19% and -21%; p = .003 to .01); IMAT and VAT decreased in all groups more than control (between-group p < .001). ISI increased more in COMB than AEX and REX groups (86% vs 50% and 39%; p = .005 to .03). PPT improved more in COMB than AEX and REX groups, while VO2peak improved more in COMB and AEX than REX group (all p < .05). Knee strength improved more in COMB and REX than AEX group (all p < .05). Changes in IMAT and VAT correlated with PPT (r = -0.28 and -0.39), VO2peak (r = -0.49 and -0.52), gait speed (r = -0.25 and -0.36), and ISI (r = -0.49 and -0.52; all p < .05)., Conclusions: Weight loss plus combination aerobic and resistance exercise was most effective in improving ectopic fat deposition and physical and metabolic function in older adults with obesity., (Published by Oxford University Press on behalf of The Gerontological Society of America 2021.)

Background: Growing evidence supports the clinical importance of evaluating frailty in older adults, with its strong outcome relevance. We aimed to assess whether the Short Physical Performance Battery (SPPB) correlates with frailty status according to phenotype and deficit accumulation models and can be used as a link between these models., Methods: We analyzed records of 1064 individuals from the Aging Study of Pyeongchang Rural Area, a population-based, prospective cohort from South Korea. Frailty was determined using the Cardiovascular Health Study (CHS) phenotype (phenotype model), 26- and 34-item frailty indices (deficit accumulation model). Associations of SPPB score and frailty with a composite outcome of mortality or long-term institutionalization were assessed. Crosswalks for SPPB, the CHS frailty phenotype, and the frailty index were created., Results: The mean age of the study population was 76.0 years, and 583 (54.8%) were women. According to the CHS phenotype, 26- and 34-item frailty indices, 242 (22.7%), 161 (15.1%), and 280 (26.3%) participants, respectively, had frailty. Sensitivities/specificities for classifying CHS phenotype, 26- and 34-item frailty indices were 0.93/0.55, 0.71/0.84, and 0.80/0.83 by SPPB cut points of ≤9, ≤6, and ≤7, respectively. C-index of SPPB score (0.78) showed a predictive ability for the composite outcome that was comparable to that of CHS frailty phenotype (0.79), 26- (0.78), and 34-item frailty indices (0.79)., Conclusions: We could create a crosswalk linking frailty phenotype and frailty index from correlations between SPPB and frailty models. This result may facilitate clinical adoption of the frailty concept in a broader spectrum of older adults., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cerebrovascular events, dementia, and cancer can contribute to physical disability with activities of daily living (ADL). It is unclear whether low-dose aspirin reduces this burden in aging populations. In a secondary analysis, we now examine aspirin's effects on incident and persistent ADL disability within a primary prevention aspirin trial in community-dwelling older adults., Methods: The ASPREE (ASPirin in Reducing Events in the Elderly) trial of daily 100 mg aspirin versus placebo recruited 19 114 healthy adults aged 70+ years (65+ years if U.S. minority) in Australia and the United States. Six basic ADLs were assessed every 6 months. Incident ADL disability was defined as inability or severe difficulty with ≥1 ADL; persistence was confirmed if the same ADL disability remained after 6 months. Proportional hazards modeling compared time to incident or persistent ADL disability for aspirin versus placebo; death without prior disability was a competing risk., Results: Over a median of 4.7 years, incident ADL disability was similar in those receiving aspirin (776/9525) and placebo (787/9589) with walking, bathing, dressing, and transferring the most commonly reported. Only 24% of incident ADL disability progressed to persistent. Persistent ADL disability was lower in the aspirin group (4.3 vs 5.3 events/1000 py; hazard ratio [HR] = 0.81, 95% confidence interval [CI]: 0.66-1.00), with bathing and dressing the most common ADL disabilities in both groups. Following persistent ADL disability, there were more deaths in the aspirin group (24 vs 12)., Discussion: Low-dose aspirin in initially healthy older people did not reduce the risk of incident ADL disability, although there was evidence of reduced persistent ADL disability., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Physical function is an independent predictor of numerous chronic diseases, but its association with all-cause mortality in older adults diagnosed with cancer has received little attention. The aim of this study was to conduct a systematic review and meta-analysis on the prospective association between physical function and all-cause mortality in older adults diagnosed with cancer., Methods: Two authors systematically searched MEDLINE, EMBASE, and SPORTDiscus databases. Prospective studies reporting associations of baseline physical function with all-cause mortality in patients aged 60 years or older diagnosed with any type of cancer were included. Hazard ratios (HR) with associated 95% confidence intervals (CI) were extracted from studies for all-cause mortality, and pooled HRs were then calculated using the random-effects inverse-variance model with the Hartung-Knapp-Sidik-Jonkman adjustment., Results: Data from 25 studies with 8109 adults diagnosed with cancer aged 60 and older were included in the study. Higher levels of physical function (short physical performance battery, HR = 0.44, 95% CI 0.29-0.67; I2 = 16.0%; timed up and go, HR = 0.40, 95% CI 0.31-0.53; I2 = 61.9%; gait speed, HR = 0.41, 95% CI 0.17-0.96; I2 = 73.3%; handgrip strength: HR = 0.61 95% CI 0.43-0.85, I2 = 85.6%; and overall, HR = 0.45 95% CI 0.35-0.57; I2 = 88.6%) were associated with a lower risk of all-cause mortality compared to lower levels of functionality. Neither age at baseline nor length of follow-up had a significant effect on the HR estimates for lower all-cause mortality risk., Conclusion: Physical function may exert an independent protective effect on all-cause mortality in older adults diagnosed with cancer., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The operational definition of resilience is elusive and resilient people are difficult to identify. We used self-reported "major health event" (srMHE) to identify resilience and evaluate the functional and mortality trajectories associated with this condition., Method: We selected from the InCHIANTI study persons aged 65 or older who could perform the Short Physical Performance Battery at baseline and attended the 3 years follow-up visit. We identified 4 groups: Controls: no srMHE and no decline in physical function; Decliners: no srMHE and decline in physical function; Resilient: srMHE and no decline in physical function; and Non-resilient: srMHE and decline in physical function. Linear mixed models and Cox regression were used to analyze changes in activities of daily living (ADL) score over 9- and 10-year mortality across groups, respectively., Results: The 313 participants that reported a srMHE had worse perceived health status and higher number of GP visits and prescribed drugs at baseline. Of these, 78 were Resilient and 235 Non-resilient; of the remaining, 136 were Controls and 277 Decliners. Compared to the Controls, Resilient had similar change of ADL score over time (β: -.03, p = .92) and mortality (hazard ratio: 1.31, 95% confidence interval: 0.76-2.23), while Decliners and Non-resilient showed significantly higher mortality and, the latter, worsening of ADL score. Additional srMHE during follow-up affected the rate of change of ADL score and mortality more in the Controls group than in the Resilient group., Conclusions: A srMHE along with repeated evaluation of physical function may be used to identify resilience in older people, and may complement the standard functional evaluation of geriatric patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Diabetes is associated with gait deficits, future falls, and disability; however, it is unclear if associations remain after controlling for relevant confounders. This study investigated (i) the effects of type II diabetes on spatiotemporal gait parameters in community-dwelling older adults and (ii) if diabetes status was independently associated with future falls and disability, after controlling for gait and other confounders., Method: Baseline data were obtained from 2608 community-dwelling adults (≥60 years) participating in The Irish Longitudinal Study on Ageing (TILDA). Diabetes was identified from self-reported doctors' diagnosis, medications, and glycated hemoglobin levels. Gait characteristics were obtained during single- and dual-task walking using a GAITRite mat (n = 2560). Incident falls and disability were collected over 4 years follow-up (n = 2473). Associations between diabetes status and gait (cross-sectional) and falls and disability (longitudinal) were investigated using regression analysis, adjusting for medications, cardiovascular health, neuropsychological function, and fall-related factors., Results: Diabetes (prevalence = 9.1%) was cross-sectionally associated with shorter dual-task step length after adjusting for covariates (β = -1.59, 95% CI: -3.10, -0.08, p < .05). Diabetes was independently associated with increased risk of future instrumental activity of daily living (IADL) difficulty in those with no prior difficulty (incidence rate ratio [IRR] = 1.51, 95% CI: 1.08, 2.11, p < .05) although dual-task step length was an important confounder in all disability models. No independent associations between diabetes and falls were observed., Conclusions: Diabetes was independently associated with shorter dual-task step length and increased risk of future IADL difficulty. Multidimensional interventions addressing poor health and function in those with diabetes may help reduce the risk of gait deficits and future disability., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: With population aging, a key question is whether new cohorts of older people are in better health than previous ones. This study aimed to compare the physical and cognitive performance of community-dwelling older adults assessed at similar age in 2005, 2010, and 2015., Methods: This repeated cross-sectional analysis used data from the Lausanne cohort 65+, a three random sample population-based study. Performance of participants aged 66-71 years in 2005 (N = 1,309), 2010 (N = 1,253), and 2015 (N = 1,328) was compared using a battery of six physical and four cognitive tests. Analyses included tests for trend across samples and multivariable linear regression models., Results: Adjusted performance in all four timed physical tests (gait speed, Timed Up-and-Go, five times chair stand, and Moberg Picking-Up) improved across samples from 2005 to 2015, by +12.7% (95% confidence interval {CI} +10.5%; +14.9%) to +20.4% (95% CI +17.7%; +23.0%) in females, and by +10.6% (95% CI +8.7%; +12.4%) to +16.7% (95% CI +13.4%; +20.0%) in males. In contrast, grip strength and balance did not improve across samples. Adjusted cognitive performance showed no change in the Trail Making Test, but worsened significantly across samples for the Mini-Mental State Examination, verbal fluency, and the clock drawing test in both females (-1.9% [95% CI -2.7%; -1.1%] to -6.7% [95% CI -8.9%; -4.6%]) and males (-2.5% [95% CI -3.4%; -1.6%] to -8.0% [95% CI -11.1%; -4.9%])., Conclusions: Over the last decade, performance of adults aged 66-71 years improved significantly in timed physical tests but worsened in most cognitive measures among later-born samples., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Real-life community mobility (CM) measures for older adults, especially those with Parkinson's disease (PD), are important tools when helping individuals maintain optimal function and quality of life. This is one of the first studies to compare an objective global positioning system (GPS) sensor and subjective self-report CM measures in an older clinical population., Methods: Over 14 days, 54 people in Ontario, Canada with early to mid-stage PD (mean age = 67.5 ± 6.3 years; 47 men; 46 retired) wore a wireless inertial measurement unit with GPS (WIMU-GPS), and completed the Life Space Assessment and mobility diaries. We assessed the convergent validity, reliability and agreement on mobility outcomes using Spearman's correlation, intraclass correlation coefficient, and Bland-Altman analyses, respectively., Results: Convergent validity was attained by the WIMU-GPS for trip frequency (rs = .69, 95% confidence interval [CI] = 0.52-0.81) and duration outside (rs = .43, 95% CI = 0.18-0.62), but not for life space size (rs = .39, 95% CI = 0.14-0.60). The Life Space Assessment exhibited floor and ceiling effects. Moderate agreements were observed between WIMU-GPS and diary for trip frequency and duration (intraclass correlation coefficients = 0.71, 95% CI = 0.51-0.82; 0.67, 95% CI = 0.42-0.82, respectively). Disagreement was more common among nonretired individuals., Conclusions: WIMU-GPS could replace diaries for trip frequency and duration assessments in older adults with PD. Both assessments are best used for retired persons. However, the Life Space Assessment may not reflect actual mobility., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Many older adults become physically and cognitively impaired. However, it is unclear whether unimpaired older adults are more likely to become physically or cognitively impaired first and if this sequence impacts mortality risk., Methods: Data came from the Mexican Health and Aging Study. The sample included 1,283 participants aged ≥60 years who were physically and cognitively unimpaired in 2001. Multinomial logistic regression was used to estimate probabilities of being unimpaired, cognitively impaired only, physically impaired only, or cognitively-physically impaired in 2003. Proportional hazard models were used to estimate mortality risk through 2015 according to physical and cognitive status in 2003., Results: The probabilities for being unimpaired, physically impaired only, cognitively impaired only, and cognitively-physically impaired in 2003 were 0.45, 0.22, 0.19, and 0.13, respectively. Older age, female sex, and arthritis were associated with significantly greater probability of becoming physically impaired only than cognitively impaired only in 2003. Cognitive impairment only (hazard ratio [HR] = 1.42, 95% confidence interval [CI] = 1.09-1.85) in 2003 but not physical impairment only (HR = 1.22, 95% CI = 0.94-1.58) was associated with greater mortality than being unimpaired in 2003. Cognitively-physically impaired participants had higher mortality risk than participants who were physically (HR = 1.58, 95% CI = 1.18-2.12) or cognitively (HR = 1.36, 95% CI = 1.01-1.84) impaired only., Discussion: The likelihood of becoming only physically or cognitively impaired over 2 years varies by demographic and health characteristics. The mortality risk for unimpaired older adults who become cognitively impaired only is similar to those who become physically impaired only. Research should determine if the sequence of cognitive and physical impairments is associated with other outcomes., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: A universal definition of sarcopenia is still lacking. Since the European criteria have been recently revised, we aimed at studying prevalence of low muscle strength (LMS) and low muscle mass (LMM), as defined according to the European Working Group of Sarcopenia in Older People (EWGSOP) 2 and 1 definitions, and their individual contribution toward mortality and incident mobility disability in a cohort of community-dwelling older people., Methods: Longitudinal analysis of 535 participants of the InCHIANTI study. LMS and LMM were defined according to the criteria indicated in the EWGSOP2 and 1. Cox and log-binomial regressions were used to examine association with mortality and 3-year mobility disability (inability to walk 400 m)., Results: We observed a lower prevalence of the combination LMM/LMS according to EWGSOP2 compared to EWGSOP1 (3.2% vs 6.2%). Using the new criteria, all sarcopenia components were associated with mortality, although the hazard ratio [HR] for the group LMM/LMS was no longer significant after adjustment for confounders (LMM: HR 2.69, 95% confidence interval [CI] 1.04-6.94; LMS: HR 3.18, 95% CI 1.44-7.01; LMM/LMS: HR 2.95, 95% CI 0.86-10.16). Using EWGSOP1, LMS alone was independently associated with mortality (HR 4.43, 95% CI 1.85-10.57). None of the sarcopenia components conferred a higher risk of mobility disability., Conclusions: The EWGSOP2 algorithm leads to a reduction in the estimated prevalence of sarcopenia defined as combination of LMM/LMS. The finding that, independent of the adopted criteria, people with LMS and normal mass have a higher mortality risk compared to robust individuals, confirms that evaluation of muscle strength has a central role for prognosis evaluation., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Multimorbidity is associated with greater disability and accelerated declines in physical functioning over time in older adults. However, less is known about its effect on cognitive decline., Methods: Participants without dementia from the Health and Retirement Study were interviewed about physician-diagnosed conditions, from which their multimorbidity-weighted index (MWI) that weights diseases to physical functioning was computed. We used linear mixed-effects models to examine the predictor MWI with the modified Telephone Interview for Cognitive Status (TICSm, global cognition), 10-word immediate recall and delayed recall, and serial 7s outcomes biennially after adjusting for baseline cognition and covariates., Results: Fourteen thousand two hundred sixty-five participants, 60% female, contributed 73,700 observations. Participants had a mean ± SD age 67 ± 9.3 years and MWI 4.4 ± 3.9 at baseline. Each point increase in MWI was associated with declines in global cognition (0.04, 95% CI: 0.03-0.04 TICSm), immediate recall (0.01, 95% CI: 0.01-0.02 words), delayed recall (0.01, 95% CI: 0.01-0.02 words), and working memory (0.01, 95% CI: 0.01-0.02 serial 7s; all p < .001). Multimorbidity was associated with faster declines in global cognition (0.003 points/year faster, 95% CI: 0.002-0.004), immediate recall (0.001 words/year faster, 95% CI: 0.001-0.002), and working memory (0.006 incorrect serial 7s/year faster, 95% CI: 0.004-0.009; all p < .001), but not delayed recall compared with premorbid slopes., Conclusions: Multimorbidity using a validated index weighted to physical functioning was associated with acute decline in cognition and accelerated and persistent cognitive decline over 14 years. This study supports an ongoing geriatric syndrome of coexisting physical and cognitive impairment in adults with multimorbidity. Clinicians should monitor and address both domains in older multimorbid adults., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The adipokine adiponectin (APN)'s role in Alzheimer's disease (AD) is controversial. Some studies suggest APN is neuroprotective while others propose it has harmful effects. We have used Multiple Indicators Multiple Causes (MIMIC) models to evaluate the effects of serum protein biomarkers on cognitive performance in the Texas Alzheimer's Research and Care Consortium (TARCC) (Royall DR, Bishnoi RJ, Palmer RF. Serum IGF-BP2 strongly moderates age's effect on cognition: a MIMIC analysis. Neurobiol Aging. 2015;36:2232-2240; Bishnoi RJ, Palmer RF, Royall DR. Vitamin D binding protein as a serum biomarker of Alzheimer's disease. J Alzheimers Dis. 2015;43:37-45; Bishnoi RJ, Palmer RF, Royall DR. Serum interleukin (IL)-15 as a biomarker of Alzheimer's disease. PLoS One. 2015;10:e0117282)., Methods: MIMIC models were constructed and replicated in randomly selected 50% splits of TARCC's data (Group 1 N = 1,691; Group 2 N = 1,690) and used to evaluate the relationship between serum APN levels and cognition. Our approach has been to divide general intelligence (Spearman's g) (Spearman C. The Abilities of Man: Their Nature and Measurement. 1932) into two latent variables, δ (ie, a dementia-specific phenotype representing the disabling fraction of cognitive variance) and g prime (g') (ie, the residual non-disabling fraction). Only effects on δ are likely to be dementing., Results: Serum APN was significantly related to δ scores (r = .10, p = .015). APN had no significant effect on g' (r = -.25, p = .66), nor did it have any independent direct effects on cognitive performance. These results were replicated across random subsets (ΔCHISQ = 2.8(7), p > .90)., Conclusions: APN's effect on cognition is mediated through intelligence (ie, δ), likely to be disabling, and therefore to mediate one or more dementing processes. We have previously shown APN to partially mediate age's-specific effect on δ (Royall DR, Al-Rubaye S, Bishnoi R, Palmer RF. Serum protein mediators of dementia and aging proper. Aging (Albany NY). 2016;8:3241-3254). However, because the current model is age adjusted, APN must mediate one or more additional age-independent dementing process(es), possibly AD., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In old age, decline in functioning may cause changes in walking ability. Our aim was to study whether older people who report adaptive, maladaptive, or no walking modifications differ in outdoor mobility., Methods: Community-dwelling people aged 75-90 years (N = 848) were interviewed at baseline, of whom 761 participated in the 2-year follow-up. Walking modifications were assessed by asking the participants whether they had modified their way of walking 2 km due to their health. Based on the responses, three categories were formed: no walking modifications (reference), adaptive (eg, walking more slowly, using an aid), and maladaptive walking modifications (reduced frequency of walking, or having given up walking 2 km). Differences between these categories in life-space mobility, autonomy in participation outdoors, and unmet physical activity need were analyzed using generalized estimation equation models., Results: Participants with maladaptive walking modifications (n = 238) reported the most restricted life-space mobility (β = -9.6, SE = 2.5, p < .001) and autonomy in participation outdoors (β = 1.7, SE = 0.6, p = .004) and the highest prevalence of unmet physical activity need (odds ratio = 4.3, 95% confidence interval = 1.1-16.5) at baseline and showed a decline in these variables over time. Those with no walking modifications (n = 285) at baseline exhibited the best values in all outdoor mobility variables and no change over time. Although at baseline those with adaptive walking modifications (n = 325) resembled those with no modifications, their outdoor mobility declined over time., Conclusion: Adopting adaptive modifications may postpone decline in outdoor mobility, whereas the use of maladaptive modifications has unfavorable consequences for outdoor mobility., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: DNA methylation (DNAm) age acceleration (AgeAccel) has been shown to be predictive of all-cause mortality but it is unclear what functional aspect(s) of aging it captures. We examine associations between four measures of AgeAccel in adults aged 45-87 years and physical and cognitive performance and their age-related decline., Methods: AgeAccelHannum, AgeAccelHorvath, AgeAccelPheno, and AgeAccelGrim were calculated in the Medical Research Council National Survey of Health and Development (NSHD), National Child Development Study (NCDS) and TwinsUK. Three measures of physical (grip strength, chair rise speed, and forced expiratory volume in one second [FEV1]) and two measures of cognitive (episodic memory and mental speed) performance were assessed., Results: AgeAccelPheno and AgeAccelGrim, but not AgeAccelHannum and AgeAccelHorvath were related to performance in random effects meta-analyses (n = 1,388-1,685). For example, a 1-year increase in AgeAccelPheno or AgeAccelGrim was associated with a 0.01 mL (95% confidence interval [CI]: 0.01, 0.02) or 0.03 mL (95% CI: 0.01, 0.05) lower mean FEV1 respectively. In NSHD, AgeAccelPheno and AgeAccelGrim at 53 years were associated with age-related decline in performance between 53 and 69 years as tested by linear mixed models (p < .05). In a subset of NSHD participants (n = 482), there was little evidence that change in any AgeAccel measure was associated with change in performance conditional on baseline performance., Conclusions: We found little evidence to support associations between the first generation of DNAm-based biomarkers of aging and age-related physical or cognitive performance in midlife to early old age. However, there was evidence that the second generation biomarkers, AgeAccelPheno and AgeAccelGrim, could act as makers of an individual's healthspan as proposed., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: Adiposity-related ventilatory constraints in older adults can potentially contribute to greater risk of exercise intolerance and mobility disability. This study investigated whether ventilatory limitation, measured by breathing reserve (BR) at peak exercise, is associated with body composition and physical function in older adults with obesity., Methods: This study was a cross-sectional analysis of data from a community-based cohort (N = 177) of older men and women (65-79 years) with obesity (body mass index = 30-45 kg/m2). All participants underwent cardiopulmonary exercise testing on a treadmill, dual-energy X-ray absorptiometry for body composition, and physical function assessments. We examined relationships between BR and body composition and physical function using multiple linear regression and compared a subset with (BR ≤ 30%; BR-low; n = 56) and without (BR ≥ 45%; BR-high, n = 48) ventilatory limitation using unpaired Student's t test and analysis of covariance., Results: BR was inversely related to total body mass, lean mass, fat mass, % body fat, and waist circumference (p < 0.05 for all). BR was positively related to 400 m walk time (p = .006) and inversely related to usual gait speed (p = .05) and VO2peak (p < .0001), indicative of worse physical function. BR-low had greater adiposity, but also greater lean mass, higher VO2peak, and faster 400 m walk time, compared to BR-high (p < .05, for all)., Conclusions: Older adults with obesity who also have ventilatory limitation have overall higher measures of adiposity, but do not have lower peak exercise capacity or physical function. Thus, ventilatory limitation does not appear to be a contributing factor to obesity-related decrements in exercise tolerance or mobility., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The age-related decline in mass, strength, and performance of skeletal muscle is associated with loss of independence, falls risk, disability, institutionalization, and death., Methods: To determine whether a cocoa supplement enriched in flavonoids can improve plasma markers of oxidative stress and inflammation, physical performance and frailty in middle-aged and older subjects, we conducted a two-phase, randomized, double-blind, clinical trial. The initial study included 60 subjects (55- to 70-year-old) allocated into placebo (P), highly alkalinized (no-flavonoid; NF), or flavonoid-rich natural cocoa (F) beverage groups. The follow-up study included 74 older subjects (65- to 90-year-old) randomly distributed into NF or F groups. Subjects were instructed to consume the beverages once/day for up to 12-weeks. A comprehensive (aging relevant) set of end points were assessed, which included mean change in blood plasma metabolic and oxidative stress indicators, in physical performance tests and quality of life (QoL)., Results: In the initial study, the F group showed improved glycemia, triglyceridemia, High-density lipoprotein cholesterol, Low-density lipoprotein cholesterol, triglyceridemia/HDL index, and oxidative markers. Performance on the Up and Go test, skeletal muscle index, and quality of life also improved. In the follow-up study, F treatment was associated with significant improvements in metabolic, oxidative stress, and inflammatory endpoints and positive effects on physical performance, frailty indicators, and quality of life (F vs. NF group)., Conclusions: Regular flavonoids consumption positively affects blood oxidative stress and inflammation end points, cardiometabolic risk markers, physical performance, and quality of life. The sum of such effects may help to mitigate the extent of frailty development in the elderly people., Trial Registration: NCT03585868., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Limited time and resources hinder the use of comprehensive geriatric assessment in acute contexts. We investigated the predictive value of a 10-minute targeted geriatric assessment (10-TaGA) for adverse outcomes over 6 months among acutely ill older outpatients., Methods: Prospective study comprising 819 acutely ill outpatients (79.2 ± 8.4 years; 63% women) in need of intensive management (eg, intravenous therapy, laboratory test, radiology) to avoid hospitalization. The 10-TaGA provided a validated measure of cumulative deficits. Previously established 10-TaGA cutoffs defined low (0-0.29), medium (0.30-0.39), and high (0.40-1) risks. To estimate whether 10-TaGA predicts new dependence in activities of daily living and hospitalization over the next 6 months, we used hazard models (considering death as competing risk) adjusted for standard risk factors (sociodemographic factors, Charlson comorbidity index, and physician estimates of risk). Differences among areas under receiver operating characteristic curves (AUROC) examined whether 10-TaGA improves outcome discrimination when added to standard risk factors., Results: Medium- and high-risk patients, according to 10-TaGA, presented a higher incidence of new activities of daily living dependence (21% vs 7%, adjusted subhazard ratio [aHR] = 2.4, 95% CI = 1.3-4.5; 40% vs 7%, aHR = 5.0, 95% CI = 2.8-8.7, respectively) and hospitalization (27% vs 13%, aHR = 2.0, 95% CI = 1.2-3.3; 37% vs 13%, aHR = 2.9, 95% CI = 1.8-4.6, respectively) than low-risk patients. The 10-TaGA remarkably improved the discrimination of models that incorporated standard risk factors to predict new activities of daily living dependence (AUROC = 0.76 vs 0.71, p < .001) and hospitalization (AUROC = 0.71 vs 0.68, p < .001)., Conclusions: The 10-TaGA is a practical and efficient comprehensive geriatric assessment tool that improves the prediction of adverse outcomes among acutely ill older outpatients., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background or Objectives: Disability in older adults is associated with low quality of life and higher mortality. Diet may be a potentially important public health strategy for disability prevention in aging. We examined the relations of the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets to functional disability in the Rush Memory and Aging Project., Methods: A total of 809 participants (mean age = 80.7 ± 7.2 years, 74% female) without functional disability at baseline were followed for an average of 5.3 years. Standardized measures for self-reported disability including, activities of daily living ADL), instrumental ADL, and mobility disability were assessed annually. The diet scores were computed based on a validated food frequency questionnaire administered at baseline., Results: In Cox proportional hazards models adjusted for age, sex, education, smoking, physical activity, and total calories, the second (hazard ratio = 0.75, 95% CI: 0.60-0.95) and third tertiles (hazard ratio = 0.67, 95% CI: 0.53-0.86) of MIND diet scores had lower rates of ADL disability compared to the lowest tertile (p for trend = .001), whereas only the third tertiles of the Mediterranean (hazard ratio = 0.73, 95% CI: 0.57-0.94) and DASH (hazard ratio = 0.75, 95% CI: 0.59-0.95) diets were significantly associated with ADL disability. Instrumental ADL disability was inversely and linearly associated with the MIND diet score only (p for trend = .04). Mobility disability was associated with the MIND (p for trend = .02), Mediterranean (p for trend = .05) and DASH (p for trend = .02) diet scores., Conclusion: These findings are encouraging that diet may be an effective strategy for the prevention of functional disability in older adults., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The Enabling Reduction of Low-grade Inflammation in Seniors (ENRGISE) Pilot Study is a multicenter randomized clinical trial examining the feasibility of testing whether omega-3 fish oil (ω-3) and the angiotensin receptor blocker losartan alone or in combination can reduce inflammation and improve walking speed in older adults with mobility impairment. We describe recruitment methods and results., Methods: Eligible participants were 70 years and older, had elevated interleukin-6 levels (2.5-30 pg/mL) and mobility impairment., Results: Of those who responded to recruitment, 83% responded to mailings. A total of 5,424 telephone screens were completed; of these, 2,011 (37.1%) were eligible for further screening. The most common reasons for ineligibility at the telephone screens were lack of mobility impairment or use of angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (n=1.789). Of the 1,305 initial screening visits, 1,087 participants had slow gait speed (<1 m/s). Of these, 701 (64%) had elevated interleukin-6 and were eligible for second screening visits. Of the 582 second screening visits, 335 (57.6%) were eligible to be randomized. A total of 289 participants (96% of goal) were randomized: 180 in the ω-3 stratum (240% of goal); 43 in the losartan (57% of goal), and 66 in the combination (44% of goal). The telephone screen and first screening visit to randomization ratio was 19 to 1 and 4.5 to 1, respectively. The estimated cost of recruitment per randomized participant was $1,782., Conclusion: Recruitment for ω-3 exceeded goals, but goals for the losartan and combination strata were not met due to the high proportion of participants taking angiotensin receptor blockers or angiotensin-converting enzyme inhibitors., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Obesity compounds aging-related declines in cardiorespiratory fitness, with accompanying fatigue and disability. This study determined the effects of two different levels of caloric restriction (CR) during aerobic training on cardiorespiratory fitness, fatigue, physical function, and cardiometabolic risk., Methods: The INFINITE study was a 20-week randomized trial in 180 older (65-79 years) men and women with obesity (body mass index = 30-45 kg/m2). Participants were randomly assigned to (i) aerobic training (EX; treadmill 4 days/wk for 30 minutes at 65%-70% of heart rate reserve), (ii) EX with moderate (-250 kcal/d) CR (EX + Mod-CR), or (iii) EX with more intensive (-600 kcal/d) CR (EX + High-CR). Cardiorespiratory fitness (peak aerobic capacity, VO2 peak, primary outcome) was determined during a graded exercise test., Results: One hundred and fifty-five participants returned for 20-week data collection (87% retention). VO2 peak increased by 7.7% with EX, by 13.8% with EX + Mod-CR, and by 16.0% with EX + High-CR, and there was a significant treatment effect (EX + High-CR = 21.5 mL/kg/min, 95% confidence interval = 19.8-23.2; EX + Mod-CR = 21.2 mL/kg/min, 95% confidence interval = 19.4-23.0; EX = 20.1 mL/kg/min, 95% confidence interval = 18.4-21.9). Both CR groups exhibited significantly greater improvement in self-reported fatigue and disability and in glucose control, compared with EX., Conclusion: Combining aerobic exercise with even moderate CR is more efficacious for improving cardiorespiratory fitness, fatigue and disability, and glucose control than exercise alone and is as effective as higher-dose CR., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Direct assessment of skeletal muscle mass in older adults is clinically challenging. Relationships between lean mass and late-life outcomes have been inconsistent. The D3-creatine dilution method provides a direct assessment of muscle mass., Methods: Muscle mass was assessed by D3-creatine (D3Cr) dilution in 1,382 men (mean age, 84.2 years). Participants completed the Short Physical Performance Battery (SPPB); usual walking speed (6 m); and dual x-ray absorptiometry (DXA) lean mass. Men self-reported mobility limitations (difficulty walking 2-3 blocks or climbing 10 steps); recurrent falls (2+); and serious injurious falls in the subsequent year. Across quartiles of D3Cr muscle mass/body mass, multivariate linear models calculated means for SPPB and gait speed; multivariate logistic models calculated odds ratios for incident mobility limitations or falls., Results: Compared to men in the highest quartile, those in the lowest quartile of D3Cr muscle mass/body mass had slower gait speed (Q1: 1.04 vs Q4: 1.17 m/s); lower SPPB (Q1: 8.4 vs Q4: 10.4 points); greater likelihood of incident serious injurious falls (odds ratio [OR] Q1 vs Q4: 2.49, 95% confidence interval [CI]: 1.37, 4.54); prevalent mobility limitation (OR Q1 vs Q4,: 6.1, 95% CI: 3.7, 10.3) and incident mobility limitation (OR Q1 vs Q4: 2.15 95% CI: 1.42, 3.26); p for trend < .001 for all. Results for incident recurrent falls were in the similar direction (p = .156). DXA lean mass had weaker associations with the outcomes., Conclusions: Unlike DXA lean mass, low D3Cr muscle mass/body mass is strongly related to physical performance, mobility, and incident injurious falls in older men., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The Short Physical Performance Battery (SPPB) is advocated as a screening tool in geriatric care for predicting future disability. We aimed to identify the leg neuromuscular attributes to be targeted in rehabilitative care among older adults with poor SPPB scores., Methods: Boston Rehabilitative Impairment Study of the Elderly (Boston RISE) participants (n = 430) underwent assessment of neuromuscular attributes (leg strength, leg velocity, trunk extensor endurance, knee flexion range of motion [ROM], ankle ROM, and foot sensation). Linear regression models examined association between each neuromuscular attribute and SPPB, adjusting for age, race, gender, comorbidity, body mass index, depression, cognition, and other neuromuscular attributes., Results: Participants with 1 SD unit higher leg strength, leg velocity, and trunk extensor endurance had 0.52, 0.30, and 0.52 points higher SPPB total score. Participants with ankle ROM impairment and foot sensory loss had 0.43 and 0.57 lower SPPB total score compared with those without these. Leg strength and trunk extensor endurance were associated with balance; leg velocity, trunk extensor endurance, and ankle ROM were associated with gait speed; and strength, trunk extensor endurance, knee ROM, and feet sensation were associated with chair stand score. Neuromuscular attributes, along with covariates, explained 40.4% of the variance in the total SPPB score, a substantial increase over the 22.7% variance explained by covariates alone., Conclusions: Neuromuscular attributes affect mobility performance in older patients as measured by the SPPB. Specific impairments are associated with poor performance in specific component scores. Assessment of the SPPB components and rehabilitation of associated impairments may help improve the functional performance among older adults., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Individuals with mild cognitive impairment (MCI), often a precursor to dementia, experience limitations in completing daily activities. These limitations are particularly important to understand, as they predict risk for dementia. Relations between functional changes and both cognitive decline and upper extremity motor impairments have been reported, but the contribution of motor function to relations between cognitive function and functional independence remains poorly understood. We examined the relationship between cognition and upper extremity activities, and whether this relation was mediated by motor function., Methods: A total of 430 community-dwelling primary care patients aged at least 65 years from the Boston Rehabilitative Impairment Study of the Elderly completed self-report measures of upper extremity function, tests of neuromuscular attributes to measure motor function (reaction time, pronosupination of the hands), and neuropsychological measures. Participants were classified based on cognitive performance into groups: MCI and without MCI, with MCI further classified by cognitive subtype. Regression and mediation analyses examined group differences and relations between cognitive function, upper extremity function, and neuromuscular attributes., Results: MCI participants demonstrated poorer neuromuscular attributes and self-reported upper extremity function, and neuromuscular attributes significantly mediated positive relations between cognitive status and self-reported upper extremity function. Poorer self-reported upper extremity function was most prominent for groups with executive dysfunction., Conclusions: Together with previous research, results suggest that the relationship between cognitive function, motor function, and functional activities is not confined to mobility tasks but universally related to body systems and functional activities. These findings inform new approaches for dementia risk screening and rehabilitative care., (Published by Oxford University Press on behalf of The Gerontological Society of America 2018.)

Background: Some clinical trials suggest that protein supplementation enhances the effects of resistance exercise on skeletal muscle mass (SMM); fewer studies examine the effects of diets rich in protein-source foods on SMM and functional status among community-dwelling adults., Methods: Data from the Framingham Offspring study including diet (three-day records, exams 3 and 5), physical activity (exams 2 and 4), percent SMM (%SMM) (exams 6 and 7), and functional performance (exams 5 through 8) were used to evaluate independent and combined effects of physical activity and high-protein foods on adjusted mean %SMM (using analysis of covariance) and risk of functional decline (using Cox proportional hazard's models). Analyses were adjusted for such factors as age, education, height, smoking, and fruit and grain consumption)., Results: Higher intakes of protein-source foods (red meat, poultry, fish, dairy, and soy, nuts, seeds and legumes) were associated with higher %SMM over 9 years, particularly among women. Men and women with higher intakes of foods from animal sources had a higher % SMM regardless of activity; beneficial effects of plant-based protein foods were only evident in physically active adults. Active subjects with higher intakes of animal or plant protein-source foods had 35% lowest risks of functional decline. Among less active individuals, only those consuming more animal protein-source foods had reduced risks of functional decline (HR: 0.7l; 95% CI: 0.50-1.01)., Conclusion: Higher intake of animal-protein foods, alone and especially in combination with a physically active lifestyle, was associated with preservation of muscle mass and functional performance in older adults., (© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Physical function decline is a major public health concern and can predict later mortality. This study aims to examine the sociodemographic factors associated with physical function decline among U.S. Chinese older adults through a longitudinal population-based study., Methods: Data were derived from the Population Study of Chinese Elderly (PINE) at two time points: 2011-2013 and 2013-2015. Physical function was measured by observed physical performance testing, including chair stand, tandem stand, and timed walk. Mixed-effect models were used to analyze the demographic risk factors associated with physical function decline., Results: Of the 2,713 participants in waves 1 and 2, their average age was 72.6 years old, 58.4% were female, with 8.7 years of education average, and 85.8% had an annual individual income of less than $10,000. Our findings show subjects of older age, female sex, lower education, lower income, and a greater number of medical comorbidities had lower physical function levels at baseline. Older adults experienced a faster decline in physical function for the overall performance measure (β = -.02, p < .001). Additionally, elderly adults with higher education have a faster decline of physical function in the overall performance measure (β = -.03, p < .01)., Discussion: As the first to examine physical function decline among U.S. Chinese older adults, our study finds older age and higher education are two factors associated with a faster rate of physical function decline. In future research, long-term follow up and multiple waves of data are needed to investigate risk or resilience factors for disability or recovering from disability., (© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Spouses of Alzheimer's disease patients (AD spouses) may experience substantial health effects associated with their partner's chronic cognitive and behavioral dysfunction. Studies examining associations between the medical experiences of AD spouses in the period before and after their partner's AD diagnosis are limited, particularly those which measure health care resource use and cost., Methods: AD patients were identified through multiple Medicare claims containing an AD diagnostic code. Their spouses were identified through special coding in the Medicare eligibility records. The AD spouses were matched demographically to the spouses of Medicare beneficiaries without a history of AD. Longitudinal and annual cross-sectional Medicare cost comparisons utilized log-transformed linear regression. The longitudinal period of observation began 12 months before the AD patient's initial claim listing AD and continued for up to 38 months afterwards., Results: The study identified 16,322 AD spouses. Total per person costs were 24% higher in AD spouses than in the controls ($694/month vs $561/month). AD spouses' excess costs began 3 months before their partners' AD diagnoses and continued for ≥30 months. Being an AD spouse predicted 29% higher Medicare costs after adjustment for chronic health status (P < .001). Increasing AD patient care complexity had a substantial impact on AD spouse Medicare costs (P < .001)., Conclusions: This study documents a link between the health status of AD spouses and AD patients. Additional research is required to elicit the mechanism behind the association between AD spouse and AD patient diagnosis., (© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The aims of this study were to determine among retirees: the associations of arthritis with limitations in physical functions, and whether these associations changed differently with age for those with arthritis versus without arthritis., Methods: We identified retirees from the Health and Retirement Study, a nationally representative longitudinal panel study of U.S. adults ≥51 years old. We calculated incidence density ratios (IDRs) using Poisson regression modeling with generalized estimating equations to estimate the associations between arthritis and limitations in four physical function measures (large muscle tasks, mobility, activities of daily living, and instrumental activities of daily living) adjusting for age, sex, race/ethnicity, marital status, education, total household income, depression, obesity, smoking, chronic conditions, physical activity, and cohort status. We examined interaction effects between arthritis and age to determine if the rate of change in physical function differed by arthritis status across age., Results: Over 8 years (2004-2012), significantly more retirees with arthritis had limitations with large muscle tasks (IDR 2.1: 95% confidence interval 1.6, 2.8), mobility (IDR 1.6: 1.2, 2.2), activities of daily living (IDR 2.2: 1.0, 4.7), and instrumental activities of daily living (IDR 3.7: 1.9, 7.4) than retirees without arthritis. Retirees with arthritis did not develop limitations in mobility, activities of daily living, and instrumental activities of daily living at a different rate as they aged compared to those without arthritis., Conclusions: Arthritis was associated with a greater prevalence of physical function limitations. Preventing limitations caused by arthritis is a key strategy to prevent disability in retirees., (Published by Oxford University Press on behalf of The Gerontological Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: The functional declines with aging relate to deficits in motor control and strength. In this study, we determine whether older adults exhibit impaired driving as a consequence of declines in motor control or strength., Methods: Young and older adults performed the following tasks: (i) maximum voluntary contractions of ankle dorsiflexion and plantarflexion; (ii) sinusoidal tracking with isolated ankle dorsiflexion; and (iii) a reactive driving task that required responding to unexpected brake lights of the car ahead. We quantified motor control with ankle force variability, gas position variability, and brake force variability. We quantified reactive driving performance with a combination of gas pedal error, premotor and motor response times, and brake pedal error., Results: Reactive driving performance was ~30% more impaired (t = 3.38; p < .01) in older adults compared with young adults. Older adults exhibited greater motor output variability during both isolated ankle dorsiflexion contractions (t = 2.76; p < .05) and reactive driving (gas pedal variability: t = 1.87; p < .03; brake pedal variability: t = 4.55; p < .01). Deficits in reactive driving were strongly correlated to greater motor output variability (R 2 = .48; p < .01) but not strength (p > .05)., Conclusions: This study provides novel evidence that age-related declines in motor control but not strength impair reactive driving. These findings have implications on rehabilitation and suggest that interventions should focus on improving motor control to enhance driving-related function in older adults., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: HMG-CoA reductase inhibitors (statins) are among the most commonly prescribed classes of medications. Although their cardiovascular benefits and myalgia risks are well documented, their effects on older adults initiating an exercise training program are less understood., Methods: 1,635 sedentary men and women aged 70-89 years with Short Physical Performance Battery (SPPB) score of 9 or below and were able to walk 400 m were randomized to a structured, moderate-intensity physical activity (PA) program consisting of both center-based (twice/wk) and home-based (3-4 times/wk) aerobic, resistance, and flexibility training or to a health education (HE) program combined with upper extremity stretching., Results: Overall, the PA intervention was associated with lower risk of major mobility disability (hazard ratio [HR] = 0.82; 95% confidence interval [CI] = 0.69-0.98). The effect was similar (p value for interaction = .62) in both statin users (PA n = 415, HE n = 412; HR = 0.86, 95% CI = 0.67-1.1) and nonusers (PA n = 402, HE n = 404; HR = 0.78, 95% CI = 0.61-1.01). Attendance was similar for statin users (65%) and nonusers (63%). SPPB at 12 months was slightly greater for PA (8.35±0.10) than for HE (7.94±0.10) in statin users but not in nonusers (PA 8.25±0.10, HE 8.16±0.10), though the interaction effect was not statistically significant. Self-reported PA levels were not different between statin users and nonusers., Conclusions: Although statins have been associated with adverse effects on muscle, data from the LIFE Study show that statin users and nonusers both benefit from PA interventions. Older adults who require statin medications to manage chronic medical conditions and are sedentary will be able to benefit from interventions to increase PA., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

At the 67th Gerontological Society of America Annual Meeting, a preconference workshop was convened to discuss the challenges of accurately assessing physical activity in older populations. The advent of wearable technology (eg, accelerometers) to monitor physical activity has created unprecedented opportunities to observe, quantify, and define physical activity in the real-world setting. These devices enable researchers to better understand the associations of physical activity with aging, and subsequent health outcomes. However, a consensus on proper methodological use of these devices in older populations has not been established. To date, much of the validation research regarding device type, placement, and data interpretation has been performed in younger, healthier populations, and translation of these methods to older populations remains problematic. A better understanding of these devices, their measurement properties, and the data generated is imperative to furthering our understanding of daily physical activity, its effects on the aging process, and vice versa. The purpose of this article is to provide an overview of the highlights of the preconference workshop, including properties of the different types of accelerometers, the methodological challenges of employing accelerometers in older study populations, a brief summary of ongoing aging-related research projects that utilize different types of accelerometers, and recommendations for future research directions., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Comorbidity (COM) is an important issue in aging. Cardiovascular disease (CVD) and osteoarthritis separately and together may modify the trajectories of functional decline. This analysis examines whether specific and unrelated COMs influence functional change differently and vary by gender., Methods: A cohort study of 1,789 (aged 60 years and older) Mexican Americans was followed annually for up to 10 years. We created four groups of COM (CVD alone, lower body osteoarthritis alone [OA], neither, or both). We employed mixed effects Poisson models with Instrumental Activities of Daily Living (IADL) as the outcome. We tested whether the association between COM and decline in functional status differed by gender., Results: IADL impairments in those with CVD, OA, or both were significantly higher at baseline and increased more rapidly over time compared to those with neither condition. Compared to women with no COM, the number of IADL impairments in women with CVD alone were 1.36 times greater, with OA were 1.35 times greater, and both conditions were 1.26 times greater. Compared to men with no COM, IADL impairments in men with CVD alone were 1.15 times greater, OA alone were 1.12 times greater, and both were 1.26 times greater., Conclusions: Over time, the influence of COM on functional decline differs by specific combinations of COM and by gender. Aggregate COM scales obscure the biological and temporal heterogeneity in the effects of COM. Time-dependent-specific COMs better assess the development of impairment. Women experience a higher burden of functional impairment due to COM than men., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Slow gait is a robust biomarker of health and a predictor of functional decline and death in older adults, yet factors contributing to the decline in gait speed with aging are not well understood. Previous research suggests that the energetic cost of walking at preferred speed is inversely associated with gait speed, but whether individuals with a rising energetic cost of walking experience a steeper rate of gait speed decline has not been investigated., Methods: In participants of the Baltimore Longitudinal Study of Aging, the energetic cost of overground walking at preferred speed (mL/kg/m) was assessed between 2007 and 2014 using a portable indirect calorimeter. The longitudinal association between the energetic cost of walking and usual gait speed over 6 meters (m/s) was assessed with multivariate linear regression models, and the risk of slow gait (<1.0 m/s) was analyzed using Cox proportional hazards models., Results: The study population consisted of 457 participants aged 40 and older who contributed 1,121 person-visits to the analysis. In fully adjusted models, increases in the energetic cost of walking predicted the rate of gait speed decline in those older than 65 years (β = -0.008 m/s, p < .001). Moreover, those with a higher energetic cost of walking (>0.17mL/kg/m) had a 57% greater risk of developing slow gait compared with a normal energetic cost of walking (≤0.17mL/kg/m; adjusted hazard ratio = 1.57, 95% confidence interval: 1.01-2.46)., Conclusions: These findings suggest that strategies to maintain walking efficiency hold significant implications for maintaining mobility in late life. Efforts to curb threats to walking efficiency should focus on therapies to treat gait and balance impairments, and reduce clinical disease burden., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Despite yoga's popularity, few clinical trials have employed rigorous methodology to systematically explore its functional benefits compared with more established forms of exercise. The objective of this study was to compare the functional benefits of yoga with the conventional stretching-strengthening exercises recommended for adults., Methods: Sedentary healthy adults (N = 118; M age = 62.0) participated in an 8-week (three times a week for 1 hour) randomized controlled trial, which consisted of a Hatha yoga group (n = 61) and a stretching-strengthening exercise group (n = 57). Standardized functional fitness tests assessing balance, strength, flexibility, and mobility were administered at baseline and postintervention., Results: A repeated measures multivariate analysis of variance showed a significant time effect for measures of balance [F(3,18) = 4.88, p < .01, partial η(2) = .45], strength [F(2,19) = 15.37, p < .001, partial η(2) = .62], flexibility [F(4,17) = 8.86, p < .001, partial η(2) = .68], and mobility [F(2,19) = 8.54, p < .002, partial η(2) = .47]. Both groups showed significant improvements on measures of balance (left-right leg and four square step); strength (chair stands and arm curls); flexibility (back scratch and sit-and-reach); and mobility (gait speed and 8-feet up and go), with partial η(2) ranging from .05 to .47., Conclusions: These data suggest that regular yoga practice is just as effective as stretching-strengthening exercises in improving functional fitness. To our knowledge, this is the first study to examine functional benefits of yoga in comparison with stretching-strengthening exercises in sedentary, healthy, community-dwelling older adults. These findings have clinical implications as yoga is a more amenable form of exercise than strengthening exercises as it requires minimal equipment and can be adapted for individuals with lower levels of functioning or disabilities., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Vestibular function declines with age, and emerging evidence suggests that vestibular loss is associated with cognitive impairment. Whether vestibular dysfunction is associated with age-related cognitive decline is unknown., Methods: We used data from the 1999-2002 National Health and Nutrition Examination Surveys to evaluate the influence of vestibular function on cognitive performance in a nationally representative sample of U.S. adults aged ≥60 years (n = 1,303). Vestibular function was measured with the modified Romberg test, and cognitive function was measured by the digit symbol substitution (DSS) score test. We also developed structural equation models (SEMs) to explore whether vestibular dysfunction and associated cognitive impairment mediate the effect of age on falls and activities of daily living (ADL) difficulty., Results: Vestibular dysfunction was present in 58% of the study population. In multivariate analyses, vestibular dysfunction was associated with a 3.4-point lower DSS score (95% confidence interval: -5.2, -1.6; p < .0001), equivalent to the effect of 5 years of age. Vestibular dysfunction was also associated with a significantly higher odds of ADL difficulty (p = .001), and with a 2.6-fold increase in the odds of falling (p = .017). SEMs suggested that vestibular function mediates 14.3% of the effect of age on cognitive performance. Further SEMs suggested that lower cognitive performance mediates the association between vestibular loss and ADL difficulty as well as falls., Conclusions: This study suggests that vestibular dysfunction partially mediates the association between age and cognitive impairment. Moreover, the cognitive impairment that results from vestibular loss may contribute to ADL difficulty and falls in older individuals., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Older adults frequently have several chronic health conditions which require multiple medications. We illustrated trends in prescription medication use over 20 years in the United States, and described characteristics of older adults using multiple medications in 2009-2010., Methods: Participants included 13,869 adults aged 65 years and older in the National Health & Nutrition Examination Survey (1988-2010). Prescription medication use was verified by medication containers. Potentially inappropriate medications were defined by the 2003 Beers Criteria., Results: Between 1988 and 2010 the median number of prescription medications used among adults aged 65 and older doubled from 2 to 4, and the proportion taking ≥5 medications tripled from 12.8% (95% confidence interval: 11.1, 14.8) to 39.0% (35.8, 42.3).These increases were driven, in part, by rising use of cardioprotective and antidepressant medications. Use of potentially inappropriate medications decreased from 28.2% (25.5, 31.0) to 15.1% (13.2, 17.3) between 1988 and 2010. Higher medication use was associated with higher prevalence of functional limitation, activities of daily living limitation, and confusion/memory problems in 2009-2010, although these associations did not remain after adjustment for covariates. In multivariable models, older age, number of chronic conditions, and annual health care visits were associated with increased odds of using both 1-4 and ≥5 medications. Additionally, body mass index, higher income-poverty ratio, former smoking, and non-black non-white race were associated with use of ≥5 medications., Conclusions: Prescription medication use increased dramatically among older adults between 1988 and 2010. Contemporary older adults on multiple medications have worse health status compared with those on less medications, and appear to be a vulnerable population., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Aging is associated with increased risk of reduced mobility. However, data on muscle components in relation to subjective and objective indicators of disability is limited., Methods: Data were from 2,725 participants (43% men) aged 74.8±4.7 years from the AGES-Reykjavik Study. At baseline, maximal isometric thigh strength (dynamometer chair), and midthigh muscle area and muscle fat infiltration were assessed with computed tomography. Usual 6 m gait speed and mobility disability were assessed at baseline and after 5.2±0.3 years. Incident mobility disability was defined as having much difficulty or unable to walk 500 m or climb-up 10 steps. A decrease of ≥0.1 m/s in gait speed was considered clinically relevant., Results: Greater strength and area were protective for mobility disability risk and gait speed decline. After adjustment for other muscle components, greater strength was independently associated with lower mobility disability risk in women odds ratios (OR) 0.78 (95% CI 0.62, 0.99), and lower decline in gait speed risk among both men OR 0.64 (0.54, 0.76), and women OR 0.72 (0.62, 0.82). Larger muscle area was independently associated with lower mobility disability risk in women OR 0.67 (0.52, 0.87) and lower decline in gait speed risk in men OR 0.74 (0.61, 0.91)., Conclusions: Greater muscle strength and area were independently associated with 15-30% decreased risk of mobility disability in women and gait speed decline in men. Among women, greater muscle strength was also associated with lower risk of gait speed decline. Interventions aimed at maintaining muscle strength and area in old age might delay functional decline., (Published by Oxford University Press on behalf of the Gerontological Society of America 2015.)

Background: For prevention and treatment of sarcopenia, defined as a decline in lean mass, reliable diagnostic criteria and cutpoints reflecting a clinically relevant threshold are indispensable. As of yet, various parameters have been proposed but no gold standard exists. The aim of this study was to compare cutpoints of appendicular lean mass related to body mass index (ALMBMI) or height (ALM/height(2)) regarding their association with self-reported physical limitations and frailty status in a sample of community-dwelling older adults., Methods: A total of 1,343 participants from the Berlin Aging Study II were included. ALM index was assessed with dual-energy X-ray absorptiometry. Limitations in physical performance were assessed via questionnaire and frailty status was defined according to the Fried criteria., Results: In a risk factor-adjusted analysis, participants with an ALMBMI below the cutpoints had 1.4-2.8 times higher odds of difficulties in several domains of physical activity (p = .031 to p < .0001) compared with participants with normal ALMBMI. In participants with low ALM/height(2), no associations with physical limitations were found. Moreover, the odds of being prefrail/frail were statistically significant for the low ALMBMI group only (odds ratio = 2.403, 95% confidence interval: 1.671-3.454, p < .0001) and not for the low ALM/height(2) group., Conclusions: This study showed striking differences between the two operational criteria ALM/height(2) and ALMBMI concerning their association with physical limitations and prefrailty/frailty. The low ALMBMI cutpoints seem suitable to detect patients at risk for negative outcomes such as frailty who might benefit from interventions targeted at improving lean mass., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Gait speed is as an important predictor of mortality, volume of medical care, hospitalization, onset of activities of daily living (ADL) disability, and nursing home placement. We examined associations between change in gait speed and change in observed performance in the instrumental ADL (IADL) in a sample of mild-to-moderately disabled older adults., Methods: Participants in the Sources of Independence in the Elderly project (n = 375) were approached to complete a 4-m gait assessment and a performance test of IADL competency at three points over 2 years. IADL competency was assessed by occupational therapists, who rated participants using the Assessment of Motor and Process Skills (AMPS) and who also made a global rating of need for help or supervision. Linear mixed models were developed to assess change in motor AMPS score relative to baseline status and change in gait speed and AMPS process scores., Results: Baseline gait and change in gait were significant correlates of change in the AMPS motor ability measures in models that adjusted for cognitive status and AMPS process ability. Even respondents with gait speeds of 1 m/s at baseline were at risk of declining AMPS motor ability and an occupational therapist rating of IADL disability if gait speed declined., Conclusions: Slowing in gait speed is an important risk factor for IADL disability in mild to moderately disabled older adults., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The prevalence of mild cognitive impairment (MCI) and mobility limitations is high among older adults. The aim of this study was to investigate the association between MCI status and both performance-based and self-report measures of mobility in community-dwelling older adults., Methods: An analysis was conducted on baseline data from the Boston Rehabilitative Impairment Study in the Elderly study, a cohort study of 430 primary care patients aged 65 or older. Neuropsychological tests identified participants with MCI and further subclassified those with impairment in memory domains (aMCI), nonmemory domains (naMCI), and multiple domains (mdMCI). Linear regression models were used to assess the association between MCI status and mobility performance in the Habitual Gait Speed, Figure of 8 Walk, Short Physical Performance Battery, and self-reported Late Life Function and Disability Instrument's Basic Lower Extremity and Advanced Lower Extremity function scales., Results: Participants had a mean age of 76.6 years, and 42% were characterized with MCI. Participants with MCI performed significantly worse than participants without MCI (No-MCI) on all performance and self-report measures (p < .01). All MCI subtypes performed significantly worse than No-MCI on all mobility measures (p < .05) except for aMCI versus No-MCI on the Figure of 8 Walk (p = .054) and Basic Lower Extremity (p = .11). Moreover, compared with aMCI, mdMCI manifested worse performance on the Figure of 8 Walk and Short Physical Performance Battery, and naMCI manifested worse performance on Short Physical Performance Battery and Basic Lower Extremity., Conclusions: Among older community-dwelling primary care patients, performance on a broad range of mobility measures was worse among those with MCI, appearing poorest among those with nonmemory MCI., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Meaningful change criteria help determine if function has improved or declined, but their magnitudes may vary across clinically relevant subgroups. We estimate meaningful decline in four common measures of physical performance in subgroups of older adults based on initial performance, demographics, chronic conditions, and health status., Methods: We used baseline (Year 1) and Year 4 data from the Health, Aging and Body Composition (Health ABC) study, a well-functioning cohort at baseline of white and black men and women (age 70-79), to evaluate the magnitude of meaningful decline in performance (6 m gait speed, 400-m walk time (400MWT), Short Physical Performance Battery, and Health ABC Physical Performance Battery (PPB), based on self-reported perceived mobility anchors (climbing 10 steps and walking ¼ mile). Estimates were stratified by initial performance, demographics, health status, chronic conditions, and body mass index, and compared across strata., Results: For all four measures, small and substantial decline estimates were generally consistent among subgroups based on initial performance, demographics, health status, and chronic conditions. The only exception was for 400MWT, where men had greater estimates than women. For PPB, small change was 0.12 points, and substantial change was 0.22 points., Conclusions: Estimates of small and substantial meaningful decline resemble those previously reported for gait speed, 400MWT, and SPPB. Magnitudes of meaningful performance decline appear to be generally consistent across strata of initial performance, demographics, health status, body mass index, and chronic conditions., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)