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Cellular senescence is a plausible mediator of age-associated declines in physical performance. To test this premise, we examined cross-sectional associations between circulating components of the senescence-associated secretory phenotype (SASP) and measures of physical function and muscle strength in 1377 older adults. We showed significant associations between multiple SASP proteins and the short physical performance battery (SPPB), its subcomponents (gait speed, balance, chair rise time), and 400-m walk time. Activin A, ICAM1, MMP7, VEGFA, and eotaxin showed strong associations based on gradient boost machine learning (GBM), and, when combined with other proteins, effectively identified participants at the greatest risk for mobility disability (SPPB score $$\le$$ ≤ 7). Senescence biomarkers were also associated with lower grip strength, and GBM identified PARC, ADAMTS13, and RANTES as top candidates in females, and MMP2, SOST, and MCP1 in males. These findings highlight an association between senescence biomarkers and physical performance in older adults. ClinicalTrials.gov Identifier: NCT01072500.

The objective of the study was to investigate functional performance and pain intensity outcomes for associations with negative cognitive orientations, avoidance behaviors, and fear of pain in older Black men with low back pain (LBP).Sixty Black men aged 60 and older (70 years[Formula: see text]) with LBP completed the Short Physical Performance Battery (SPPB), the 400-m walk test, and subjective measures of avoidance behaviors, back performance, pain intensity, and pain catastrophizing (i.e., rumination, magnification, and helplessness). Multiple regression models were used to examine associations.Higher helplessness scores were associated with worse back performance (ß = 0.55, p = 0.02), slower walking speed (ß = 0.30, p = 0.02), and higher average pain intensity (ß = 0.22, [Formula: see text] p = 0.03). Higher rumination scores were associated with better back performance (ß = - 0.36, p = 0.04). Avoidance behaviors, fear of pain, and magnification were not significantly associated with any of the variables included in the tested models.Negative cognitive internalization is associated with limitations in functional performance in older Black men with LBP. Additional research is needed to further examine the cognitive orientations for understanding experienced pain and function in this population. Such research may inform the development of interventions for improving functional performance outcomes of older Black men with LBP.

Introduction: We aim to provide guidance on outcomes and measures for use in patients with Alzheimer's clinical syndrome. Methods: A consensus group of 20 voting members nominated by 10 professional societies, and a non-voting chair, used a Delphi approach and modified GRADE criteria. Results: Consensus was reached on priority outcomes (n = 66), measures (n = 49) and statements (n = 37) across nine domains. A number of outcomes and measurement instruments were ranked for: Cognitive abilities; Functional abilities/dependency; Behavioural and neuropsychiatric symptoms; Patient quality of life (QoL); Caregiver QoL; Healthcare and treatment-related outcomes; Medical investigations; Disease-related life events; and Global outcomes. Discussion: This work provides indications on the domains and ideal pertinent measurement instruments that clinicians may wish to use to follow patients with cognitive impairment. More work is needed to develop instruments that are more feasible in the context of the constraints of clinical routine.

BACKGROUND Up to 15% of people aged 60 and over are anemic, and the prevalence of anemia increases with age. In older men and women, anemia is associated with increases in the risk of death and all-cause hospitalization, poor functional capacity, quality of life, and depression. METHODS AND RESULTS We reviewed the literature describing anemia in aging populations, focusing on the specific diagnostic criteria of anemia and potential causes in older men and women. Even after extensive etiologic workup that involves careful medical history, physical examination, laboratory measurements, and additional studies such as bone marrow biopsy, anemia of aging is unexplained in up to 40% of older patients with anemia. As a result, treatment options remain limited. CONCLUSIONS The prevalence of unexplained anemia of aging (UAA; also called unexplained anemia of the elderly, UAE), its deleterious impacts on health, physical function, and quality of life, and the lack of effective treatment or therapy guidelines represent a compelling unmet clinical need. In this review and consensus document, we discuss the scope of the problem, possible causes of UAA, diagnostic criteria, and potential treatment options. Because even mild anemia is strongly linked to poor clinical outcomes, it should receive clinical attention rather than simply being considered a normal part of aging.

Background Pain is common among individuals with Alzheimer’s disease and related dementias (ADRD), and use of opioids has been increasing over the last decade. Yet, it is unclear to what extent opioids are appropriately prescribed for patients with ADRD and whether the appropriateness of opioid prescribing differs by ADRD status. The objective of this study is to compare the quality of opioid prescribing among patients with or without ADRD who have chronic noncancer pain. Methods A nationally representative cohort study of Medicare beneficiaries aged 50 years or older who had chronic pain but who had no cancer, hospice, or palliative care from 2011 to 2015. Four indicators of potentially inappropriate opioid prescribing were measured in patients residing in communities (75,258 patients with and 435,870 patients without ADRD); five indicators were assessed in patients in nursing homes (NHs) (37,117 patients with and 5128 patients without ADRD). Each indicator was calculated as the proportion of eligible patients with inappropriate opioid prescribing in the year after a chronic pain diagnosis. Differences in proportions between ADRD and non-ADRD groups were estimated using a generalized linear model adjusting for covariates through inverse probability weighting. Results Patients with ADRD versus those without had higher concurrent use of opioids and central nervous system–active drugs (community 44.1% vs 33.3%; NH 58.8% vs 54.1%, both P P P = 0.003) but lower use in NHs (26.9% vs 36.0%, P Conclusion Potential inappropriate opioid prescribing in 2 areas of pain care was more common among patients with ADRD than among patients without ADRD in community or NH settings. Further studies aimed at understanding the factors and effects associated with opioid prescribing patterns that deviate from guidelines are warranted.

BACKGROUND: Accurate estimates of clinically important difference (CID) are required for interpreting the clinical importance of treatments to improve physical function, but CID estimates vary in different disease populations. AIMS: We determined the CID of 6-minute walking distance (6MWD) and physical function component (PF10) of Medical Outcomes Study Short Form-36 in mobility-limited older men using the Testosterone Trials (TTrials) data. METHODS: TTrials participants (n=429) with mobility limitation and gait speed

BACKGROUND The Sarcopenia Definitions and Outcomes Consortium (SDOC) is a collaborative initiative seeking to develop and evaluate cut-points for low muscle strength and lean mass that predict an increased risk for slowness (usual walking speed

Background Advances in computational algorithms and the availability of large datasets with clinically relevant characteristics provide an opportunity to develop machine learning prediction models to aid in diagnosis, prognosis, and treatment of older adults. Some studies have employed machine learning methods for prediction modeling, but skepticism of these methods remains due to lack of reproducibility and difficulty in understanding the complex algorithms that underlie models. We aim to provide an overview of two common machine learning methods: decision tree and random forest. We focus on these methods because they provide a high degree of interpretability. Method We discuss the underlying algorithms of decision tree and random forest methods and present a tutorial for developing prediction models for serious fall injury using data from the Lifestyle Interventions and Independence for Elders (LIFE) study. Results Decision tree is a machine learning method that produces a model resembling a flow chart. Random forest consists of a collection of many decision trees whose results are aggregated. In the tutorial example, we discuss evaluation metrics and interpretation for these models. Illustrated using data from the LIFE study, prediction models for serious fall injury were moderate at best (area under the receiver operating curve of 0.54 for decision tree and 0.66 for random forest). Conclusions Machine learning methods offer an alternative to traditional approaches for modeling outcomes in aging, but their use should be justified and output should be carefully described. Models should be assessed by clinical experts to ensure compatibility with clinical practice.

OBJECTIVES: While Minimum Data Set (MDS) 3.0 has adopted Patient Health Questionnaire (PHQ)-9 to screen for depression and rephrased language for behavioral symptoms among nursing home residents, it remains unclear how well the assessment data agree with external sources. This study aimed at assessing the agreement of these two mental health conditions between MDS 3.0 and medical records. DESIGN: Using a retrospective review of MDS 3.0 linked to medical diagnostic records between October 2010 and November 2017, we included residents with at least one quarterly or short-term (day 30 or day 60) MDS-3.0 assessment of depression PHQ-9 (n=446) or behavioral symptoms (including psychosis, physical, verbal or other aggressive behaviors) (n=460). For each resident of each cohort, we randomly selected an eligible MDS-3.0 depression and behavioral symptom assessment and compared against the respective medical diagnoses recorded within 30 days before the MDS-3.0 assessment. RESULTS: Percent agreement was high for depression (90.1%) and behavioral symptoms (89.3%). The negative agreement was also high for depression (94.8%) and behavioral symptoms (94.3%), while the positive agreement was low for both conditions (4.3% and 10.9%). CONCLUSION: MDS-3.0 assessed depression and behavioral symptoms had a high overall and negative agreement, but a low positive agreement with clinician diagnoses. MDS 3.0 data may be useful in ruling out depression and behavioral symptoms. Confirmation of the findings in a representative sample of nursing homes is warranted.

Epidemiologic evidence reporting the role of frailty in survival among older adults with a prior cancer diagnosis is limited.A total of 2050 older adults (≥60 years old) surviving for at least 1 year after a cancer diagnosis and 9474 older adults without a cancer history from the National Health and Nutrition Examination Survey (1999-2014) were included for analysis. The exposure variable, a 45-item frailty index (FI), was categorized on the basis of validated cutoffs (FI ≤ 0.10 [fit], 0.10FI ≤ 0.21 [prefrail], and FI0.21 [frail]). All-cause mortality was ascertained via the National Death Index. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence interval (CIs) for the FI, and this was followed by restricted cubic splines depicting dose-response curves.For older cancer survivors, the mean age at the baseline was 72.6 years (SD, 7.1 years); 5.9% were fit, 38.2% were prefrail, and 55.9% were frail. Older adults without a cancer history were slightly younger (mean age, 70.0 years) and less frail (47.9% were frail). At each level of the FI, cancer survivors (1.9 per 100 person-years for FI ≤ 0.10, 3.4 per 100 person-years for 0.10FI ≤ 0.21, and 7.5 per 100 person-years for FI0.21) had higher mortality than their cancer-free counterparts (1.4 per 100 person-years for FI ≤ 0.10, 2.4 per 100 person-years for 0.10FI ≤ 0.21, and 5.4 per 100 person-years for FI0.21). The multivariable model suggested a positive association between the FI and all-cause mortality for survivors (aHR for FI0.21 vs FI ≤ 0.10, 2.80; 95% CI, 1.73-4.53) and participants without a cancer history (aHR for FI0.21 vs FI ≤ 0.10, 2.75; 95% CI, 2.29-3.32). Restricted cubic splines indicated that all-cause mortality risk increased with the FI in a monotonic pattern.Frailty is associated with a higher risk of death in older cancer survivors and the elderly without a cancer history.

Interleukin (IL)-6 is a well-accepted biomarker of chronic low-grade inflammation possibly conditioning the effect of physical activity (PA) intervention on physical performance in mobility-limited older adults. We evaluated PA intervention effects on 400 m gait speed by yearly change of IL-6 levels in a post-hoc analysis from Lifestyle Interventions and Independence for Elders (LIFE) Study, a multicenter single-blind randomized clinical trial on 1300 sedentary older adults (mean age:78.85 ± 5.23,65.85 % women) at risk for mobility disability. We compared the intervention effects on 400 m gait speed at 12 months follow-up, according to yearly IL-6 change categorized for 1 pg/ml increase or decrease, and subsequently for larger range of yearly variation. Among subjects with yearly IL-6 change between -1 and + 2 pg/ml, we observed a significant difference of gait speed in PA intervention group compared to healthy educational intervention group [0.041 m/s,95 % confidence interval (CI):0.008-0.074,p = 0.006;Cohen's d:0.26, 95 % CI:0.12-0.41). No effects were observed on 400 m gait speed for wider range of variation of plasma IL-6 levels. Limiting change of IL-6 levels under this specific hormetic window could be an important goal to achieve better benefit from PA intervention in terms of gait speed change and prevention of mobility disability.

Objectives Our aim was to examine the impacts of baseline fatigue on the effectiveness of a physical activity (PA) intervention to prevent major mobility disability (MMD) and persistent major mobility disability (PMMD) in participants from the Lifestyle Interventions and Independence for Elders (LIFE) study. Design Prospective cohort of individuals aged 65 years or older undergoing structured PA intervention or health education (HE) for a mean of 2.6 years. Setting LIFE was a multicenter eight-site randomized trial that compared the efficacy of a structured PA intervention with an HE program in reducing the incidence of MMD. Participants Study participants (N = 1591) at baseline were 78.9 ± 5.2 years of age, with low PA and at risk for mobility impairment. Measurements Self-reported fatigue was assessed using the modified trait version of the Exercise-Induced Feelings Inventory, a six-question scale rating energy levels in the past week. Responses ranged from 0 (none of the time) to 5 (all of the time). Total score was calculated by averaging across questions; baseline fatigue was based on the median split: 2 or higher = more fatigue (N = 856) and lower than 2 = less fatigue (N = 735). Participants performed a usual-paced 400-m walk every 6 months. We defined incident MMD as the inability to walk 400-m at follow-up visits; PMMD was defined as two consecutive walk failures. Cox proportional hazard models quantified the risk of MMD and PMMD in PA vs HE stratified by baseline fatigue adjusted for covariates. Results Among those with higher baseline fatigue, PA participants had a 29% and 40% lower risk of MMD and PMMD, respectively, over the trial compared with HE (hazard ratio [HR] for MMD = .71; 95% confidence interval [CI] = .57-.90; P = .004) and PMMD (HR = .60; 95% CI = .44-.82; P = .001). For those with lower baseline fatigue, no group differences in MMD (P = .36) or PMMD (P = .82) were found. Results of baseline fatigue by intervention interaction was MMD (P = .18) and PMMD (P = .05). Conclusion A long-term moderate intensity PA intervention was particularly effective at preserving mobility in older adults with higher levels of baseline fatigue. J Am Geriatr Soc 68:619-624, 2020.

OBJECTIVES Decline in physical function is associated with older age. Healthcare utilization and expenditures related to physical functioning declines will likely increase as the proportion of the population of older adults rises. This study evaluated resource utilization associated with differences in physical functioning in a nationally representative sample of older adults. DESIGN A retrospective panel study nationally representative for 26 809 552 older adults in the United States. SETTING Medical Expenditure Panel Survey (MEPS) data from 2013 to 2014. PARTICIPANTS Adults aged 70 years or older who completed both rounds of the Self-Administered Questionnaire in MEPS. MEASUREMENTS Physical Component Score (PCS) from the Short-Form Health Survey as a measure of physical functioning was stratified into quartiles. Healthcare utilization (count of medical visits by setting) and total expenditures were assessed during and after the PCS measurements. Generalized linear mixed models, adjusted for demographic and clinical covariates, estimated the relationship between healthcare utilization and physical functioning. RESULTS The lowest functional status (Q1) was associated with significantly increased healthcare utilization of emergency department, inpatient, home health, outpatient, and total medical visits compared with the three higher quartiles groups (P

PURPOSE: To examine whether long-term fish oil (FO) supplementation is associated with a lower risk of mobility disability and enhances benefits of physical activity. METHODS: 1635 sedentary adults aged 70 to 89 years from the Lifestyle Interventions and Independence for Elders (LIFE) single-blinded randomized, multi-center clinical trial, which compared a structured physical activity (PA) program to a health education (HE) program. Primary outcome was incident major mobility disability (MMD), defined by loss of ability to walk 400m, measured every 6 months for an average of 2.6 years. Secondary outcomes included persistent mobility disability (PMD), Short Physical Performance Battery (SPPB), 400m walk speed, and grip strength. RESULTS: A third of participants reported using FO at baseline (456, 28%; mean age, 78.5 years; 70.5% women). MMD was experienced by 131 participants (28.7%) in the FO group and 405 (34.4%) participants in the nonuser group. After adjusting for confounders, FO supplementation was associated with a lower risk (hazard ratio [HR], 0.78; 95% CI, 0.64–0.96) of incident MMD. However, there was no interaction (P= .19) between FO supplementation and PA intervention for MMD. For the secondary outcome of PMD, the intervention association differed by supplementation (P= .002) with PA intervention associations of (HR, 1.36; 95% CI, 0.83–2.23) for users and (HR, 0.61; 95% CI, 0.46–0.81) for nonusers. Changes in physical performance outcomes were not modified by baseline FO supplementation or combination with PA. CONCLUSIONS: FO supplementation was associated with a lower risk of major mobility disability in low to moderate functioning older adults. However, supplementation did not enhance the benefit of physical activity on risk of mobility disability. These results are hypothesis generating and need to be confirmed in randomized trials.

People aging with HIV (PAWH) infection experience greater impairments in physical and cognitive function, in addition to higher rates of peripheral comorbid conditions (e.g., renal failure, diabetes, bone fracture, hypertension, cardiovascular disease, polypharmacy, and multimorbidity). While multifactorial drivers, including HIV infection itself, antiretroviral therapy-related toxicities, disparities in care, and biobehavioral factors, likely contribute, there remains an overarching question as to what are the relevant age-related mechanisms and models that could inform interventions that promote health span and life span in PAWH? This workshop was convened to hear from experts on the biology of aging and HIV researchers studying PAWH to focus on advancing investigations at the interface of HIV and Aging. In this study, we summarize the discussions from the Harvard Center for AIDS Research and Boston Claude D. Pepper cosponsored workshop on HIV and Aging, which took place in October 2018.

Context Prostate-specific antigen (PSA) changes during testosterone treatment of older hypogonadal men have not been rigorously evaluated. Design Double-blinded, placebo-controlled trial. Setting Twelve US academic medical centers. Participants Seven hundred ninety hypogonadal men ≥65 years of age with average testosterone levels ≤275 ng/dL. Men at high risk for prostate cancer were excluded. Interventions Testosterone or placebo gel for 12 months. Main Outcomes Percentile changes in PSA during testosterone treatment of 12 months. Results Testosterone treatment that increased testosterone levels from 232 ± 63 ng/dL to midnormal was associated with a small but substantially greater increase (P < 0.001) in PSA levels than placebo treatment. Serum PSA levels increased from 1.14 ± 0.86 ng/mL (mean ± SD) at baseline by 0.47 ± 1.1 ng/mL at 12 months in the testosterone group and from 1.25 ± 0.86 ng/mL by 0.06 ± 0.72 ng/mL in the placebo group. Five percent of men treated with testosterone had an increase ≥1.7 ng/mL and 2.5% of men had an increase of ≥3.4 ng/mL. A confirmed absolute PSA >4.0 ng/mL at 12 months was observed in 1.9% of men in the testosterone group and 0.3% in the placebo group. Four men were diagnosed with prostate cancer; two were Gleason 8. Conclusions When hypogonadal older men with normal baseline PSA are treated with testosterone, 5% had an increase in PSA ≥1.7 ng/mL, and 2.5% had an increase ≥3.4 ng/mL.

OBJECTIVES Proton pump inhibitors (PPIs) and histamine2 receptor antagonists (H2 RAs) are associated with pharmacologic effects that may be detrimental to mobility and response to physical activity. Mobility disability and injurious fall outcomes in PPI and H2 RA users were compared with nonusers in this secondary analysis of data from the Lifestyle Interventions for Elders (LIFE) study. METHODS Participants ages 70-89 years were randomized to a physical activity (PA) or successful aging intervention and evaluated by medication use. Confounders included baseline demographic characteristics, physical function, cognitive function, sleep quality, and acid reflux symptoms that were adjusted via propensity score weighting. Outcomes were incident and persistent major mobility disability (MMD and pMMD) and injurious falls. Weighted proportional hazard models evaluated independent and interaction effects of PPIs and H2 RAs. RESULTS No interaction was found between PPIs and H2 RAs and the PA intervention. Drug use associations were significant for H2 RAs (hazard ratio [HR] 1.74 [95% confidence interval [CI] 1.12-2.68]) and PPIs (HR 1.32 [95% CI 1.02-1.70]) compared with nonusers for pMMD. PPIs were associated with increased injurious falls compared with nonusers (HR 1.44 [95% CI 1.06-1.96]). Pooling of data from the H2 RA and PPI exposure groups showed a 26% increase in MMD (HR 1.26 [95% CI 1.07-1.48]), a 44% increase in pMMD (HR 1.44 [95% CI 1.16-1.77]), and a 48% increase in injurious falls (HR 1.48 [95% CI 1.15-1.91]) compared with nonusers. All direct comparisons between PPIs and H2 RAs were nonsignificant. CONCLUSIONS Compared with nonusers, participants using either PPIs or H2 RAs had an increased risk of MMD, pMMD, and injurious falls. It is not known if these effects are related to the individual pharmacology of each medication, reduced acid secretion, or the underlying disease state. Further study is required to determine causality.

Background Lack of consensus on how to diagnose sarcopenia has limited the ability to diagnose this condition and hindered drug development. The Sarcopenia Definitions and Outcomes Consortium (SDOC) was formed to develop evidence-based diagnostic cut points for lean mass and/or muscle strength that identify people at increased risk of mobility disability. We describe here the proceedings of a meeting of SDOC and other experts to discuss strategic considerations in the development of evidence-based sarcopenia definition. Methods Presentations and panel discussions reviewed the usefulness of sarcopenia as a biomarker, the analytical approach used by SDOC to establish cut points, and preliminary findings, and provided strategic direction to develop an evidence-based definition of sarcopenia. Results The SDOC assembled data from eight epidemiological cohorts consisting of 18,831 participants, clinical populations from 10 randomized trials and observational studies, and 2 nationally representative cohorts. In preliminary assessments, grip strength or grip strength divided by body mass index was identified as discriminators of risk for mobility disability (walking speed Conclusions International consensus on an evidence-based definition of sarcopenia is needed. Grip strength—absolute or adjusted for body mass index—is an important discriminator of mobility disability and other endpoints. Additional research is needed to develop a predictive risk model that takes into account sarcopenia components as well as age, sex, race, and comorbidities.

Objectives Limited cohort studies have assessed the association between uncontrolled pain and risk for behavioral and psychological symptoms of dementia (BPSDs). We conducted a longitudinal cohort study to examine whether associations exist between uncontrolled pain and risk for 2 common BPSDs—depression and behavioral symptoms—among long-term care (LTC) residents with Alzheimer disease and related dementia (ADRD). Design This retrospective cohort study analyzed quarterly data from the 5% Medicare sample linked to Minimum Data Set (MDS) 3.0 between January 1, 2011, and December 31, 2015. Setting and Participants LTC residents aged 50 years or older with ADRD who had chronic pain and at least 2 quarterly MDS 3.0 assessments. Methods LTC residents were followed up quarterly from first observed quarterly MDS 3.0 until first outcome event or last observed quarterly MDS 3.0. Uncontrolled pain was defined as numerical rating scale >4, verbal descriptor scale of moderate or severe pain, or ≥1 pain indicators on the Checklist of Nonverbal Pain Indicators. Depression was defined as ≥10 on the Patient Health Questionnaire 9; behavioral symptoms were defined as the presence of psychotic (delusions or hallucinations) or disruptive behaviors (rejection of care, or physical, verbal, or other aggressive behaviors). Generalized linear models (GLMs) with marginal structural modeling (MSM) stabilized weights were used to examine uncontrolled pain and outcome risk. Results The incidence rate of depression and behavioral symptoms during follow-up was 9.4 and 23.1 per 100 resident-years, respectively. Results from the MSM-GLMs showed that LTC residents with uncontrolled pain had a higher risk than those with controlled pain for developing depression [hazard ratio 1.67, 95% confidence interval (CI) 1.54–1.81] and behavioral symptoms (hazard ratio 1.28, 95% CI 1.19–1.37). Conclusions and Implications Uncontrolled pain was associated with elevated risk for depressive and behavioral symptoms in dementia, underscoring the importance of pain assessment and control among LTC residents with ADRD.

Frailty is a geriatric syndrome represented by susceptibility to precipitating health events and reduced functional reserve. Frailty can be difficult to measure in clinical practice and research. One approach to approximate frailty is based on a deficit accumulation approach, which assesses a larger number of less specific measures such as the presence of comorbidities, physical or cognitive assessments, and lab tests, and summarizes these as a frailty index. The objective of this study was to develop such an index using the Lifestyle Interventions and Independence for Elders (LIFE) Study and evaluate the validity of the frailty measure derived based on baseline information via its association with the primary outcomes of the trial, namely major mobility disability (MMD) and persistent MMD (pMMD). Further, this study aimed to evaluate the effectiveness of the physical activity intervention among participants based on their baseline frailty score. Subjects in the LIFE Study were evaluated at baseline for demographics, clinical history, and a battery of physical and cognitive functioning assessments. In total, 75 possible deficits were scored either as present (yes/no) or based on each score&rsquo, s quintiles for score-based assessments. The frailty index was measured as the total sum of deficits divided by the total number of possible deficits on a continuous scale between 0 and 100 (i.e., percent of deficits present). The frailty index was further divided into quintiles for comparison. A proportional hazards model was estimated for the MMD outcome controlling for other baseline information. A data driven approach was also used to determine relevant cut-offs in the frailty index where the trial intervention appeared to be modified. Among 1635 trial participants, the mean frailty index was 30.4 &plusmn, 6.6 and normally distributed. Over 2.5 years of average follow-up, 14.6%, 16.5%, 18.6%, 22.6%, and 27.6% of participants experienced MMD in quintiles 1&ndash, 5, respectively. Each 1-unit increase in the frailty index increased the hazard of MMD by 4% (2&ndash, 5%), and there was a nearly 2-fold increase in MMD between the highest and lowest frailty quintiles. Using log-rank criteria, a cut-point at the median was identified. Further, iterations tested for a frailty cut-off and indicated a subgroup beyond the 85th percentile wherein the physical activity intervention appeared to be no longer be effective. This internally derived deficit accumulation frailty index was uniquely able to identify individuals at higher risk of MMD and pMMD and showed that along the spectrum of frailty, the physical activity intervention remained effective for the majority of participants.

Anticholinergic cognitive burden (ACB) may be associated with detrimental effects on mobility and physical independence in older adults. We evaluated the incidence of major mobility disability (MMD), persistent major mobility disability (PMMD), and injurious falls among participants within the Lifestyle Interventions for Elders (LIFE) trial according to varied anticholinergic burden levels. Participants aged 70&ndash, 89 years were randomized to a physical activity (PA) or successful aging (SA) intervention and evaluated by ACB medication use as a summed score of a previously developed ACB scale. Confounders included demographic characteristics, physical function, cognitive function, and fall history. Average participant follow-up was 2.6 years and included outcome assessment for MMD, PMMD, and injurious falls every six months. Adjusted proportional hazards models evaluated the independent effects of ACB scores as well as interaction effects with the intervention. Of the 1635 participants, 986 (60%) used &ge, 1 anticholinergic medication. Compared to those with no burden, participants with an ACB score of 1 demonstrated increased MMD (HR = 1.42 [1.13&ndash, 1.78]), PMMD (HR = 1.53 [1.12&ndash, 2.09]), and injurious falls (HR = 1.60 [1.10&ndash, 2.32]). Results similar in magnitude were observed for all other ACB levels versus the no burden group. Stepwise dose&ndash, response comparisons between ACB groupings did not demonstrate significant differences in outcomes. Stratification by PA or SA interventions demonstrated few differences from the combined overall trial results. Compared to those not taking anticholinergic medications, participants taking anticholinergic medications generally demonstrated increased risk of MMD, PMMD, and injurious falls. Total anticholinergic burden was not associated with a stepwise dose&ndash, response relationship in mobility disability and may lack sensitivity to capture varied responses.

Short Physical Performance Battery (SPPB) assessment is a widely used measure of lower extremity function, strength, and balance. In the Lifestyles Interventions and Independence for Elders (LIFE) Study, baseline SPPB and changes throughout the trial were strongly associated with major mobility disability (MMD). This study further investigated this association by identifying trajectories of SPPB and evaluating the predictive validity of SPPB trajectories for future MMD. Participants (n = 1635) aged 70&ndash, 89 years were randomized to a physical activity or health education intervention and assessed every 6 months for MMD. We used group-based trajectory models (GBTMs) to identify trajectories of a binary outcome for a decrease from baseline SPPB of &ge, 1. Multinomial logistic regression explored baseline factors associated with group membership. Survival analyses evaluated the association between trajectories with MMD. The GBTM identified a 3-group model which included a &ldquo, No Decline&rdquo, group (46.0%), &ldquo, Late Decline&rdquo, group (27.7%), and an &ldquo, Early Decline&rdquo, group (26.3%). Adjusting for all other baseline characteristics, group assignment during the previous follow-up visit was strongly associated with MMD at the subsequent period. Comparisons between groups showed a 2-to-3-fold increase in MMD comparing the &ldquo, Late&rdquo, to &ldquo, No&rdquo, decline group and a 4-to-5-fold increase in MMD comparing the &ldquo, Early&rdquo, decline group. Group membership and impact on MMD was not different between intervention arms. Group-based trajectories of SPPB scores identified distinct subgroups in LIFE Study participants. Using these group assignments in outcome models were highly associated with MMD. GBTMs have potential to identify and improve prediction of aging-related decline to better design and identify patients for interventions.

Background This study evaluated the association between ratings of perceived exertion (RPE) of walking and major mobility disability (MMD), as well as their transitions in response to a physical activity (PA) compared to a health education (HE) program. Methods Older adults (n = 1633) who were at risk for mobility impairment were randomized to structured PA or HE programs. During a 400 m walk, participants rated exertion as “light” or “hard.” An MMD event was defined as the inability to walk 400 m. MMD events and RPE values were assessed every 6 months for an average of 2.6 years. Results Participants rating their exertion as “hard” had a nearly threefold higher risk of MMD compared with those rating their exertion as “light” (HR: 2.61, 95% CI: 2.19–3.11). The association was held after adjusting for disease conditions, depression, cognitive function, and walking speed (HR: 2.24, 95% CI: 1.87–2.69). The PA group was 25% more likely to transition from “light” to “hard” RPE than the HE group (HR: 1.25, 95% CI: 1.05–1.49). Additionally, the PA group was 27% (HR: 0.73, 95% CI: 0.55 – 0.97) less likely to transition from a “hard” RPE to inability to walk 400 m and was more likely to recover their ability to walk 400 m by transitioning to a “hard” RPE (HR: 2.10, 95% CI: 1.39–3.17) than the HE group. Conclusions Older adults rating “hard” effort during a standardized walk test were at increased risk of subsequent MMD. A structured PA program enabled walking recovery, but was more likely to increase transition from “light” to “hard” effort, which may reflect the greater capacity to perform the test.

Background Elevated interleukine-6 (IL-6) and C-reactive protein (CRP) are associated with aging-related reductions in physical function, but little is known about their independent and combined relationships with major mobility disability (MMD), defined as the self-reported inability to walk a quarter mile. Methods We estimated the absolute and relative effect of elevated baseline IL-6, CRP, and their combination on self-reported MMD risk among older adults (≥68 years; 59% female) with slow gait speed ( Results We found higher MMD risk per unit increase in log IL-6 (hazard ratio [HR] = 1.26; 95% confidence interval [95% CI] 1.13–1.41). IL-6 meeting predetermined threshold considered to be high (>2.5 pg/mL) was similarly associated with higher risk of MMD (HR = 1.31; 95% CI 1.12–1.54). Elevated CRP (CRP >3.0 mg/L) was also associated with increased MMD risk (HR = 1.38; 95% CI 1.10–1.74). The CRP effect was more pronounced among participants with elevated IL-6 (HR = 1.62; 95% CI 1.12–2.33) compared to lower IL-6 levels (HR = 1.19; 95% CI 0.85–1.66). Conclusions High baseline IL-6 and CRP were associated with an increased risk of MMD among older adults with slow gait speed. A combined biomarker model suggests CRP was associated with MMD when IL-6 was elevated.

Background The movement profile of older adults with compromised function is unknown, as is the relationship between these profiles and the development of major mobility disability (MMD)—a critical clinical outcome. We first describe the dimensions of movement in older adults with compromised function and then examine whether these dimensions predict the onset of MMD. Methods Older adults at risk for MMD (N = 1,022, mean age = 78.7 years) were randomized to receive a structured physical activity intervention or health education control. We assessed MMD in 6-month intervals (average follow-up of 2.2 years until incident MMD), with activity assessed at baseline, 6-, 12- and 24-month follow-up via accelerometry. Results A principal components analysis of 11 accelerometer-derived metrics yielded three components representing lifestyle movement (LM), extended bouts of moderate-to-vigorous physical activity (MVPA), and stationary body posture. LM accounted for the greatest proportion of variance in movement (53%). Within health education, both baseline LM (HR = 0.74; 95% CI 0.62 to 0.88) and moderate-to-vigorous physical activity (HR = 0.69; 95% CI 0.54 to 0.87) were associated with MMD, whereas only LM was associated with MMD within physical activity (HR = 0.74; 95% CI 0.61 to 0.89). There were similar nonlinear relationships present for LM in both physical activity and health education (p < .04), whereby risk for MMD was lower among individuals with higher levels of LM. Conclusions Both LM and moderate-to-vigorous physical activity should be central in treatment regimens for older adults at risk for MMD. Trial Registration clinicaltrials.gov Identifier NCT01072500

ObjectiveTo determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia.DesignEvaluator blinded, randomised controlled trial.Setting16 clinical sites across 11 European countries, January 2016 to 31 October 2019.Participants1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls).InterventionsThe multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control participants received education on healthy ageing once a month. Interventions and follow-up lasted for up to 36 months.Main outcome measuresThe primary outcome was mobility disability (inability to independently walk 400 m in ResultsMean age of the 1519 participants (1088 women) was 78.9 (standard deviation 5.8) years. The average follow-up was 26.4 (SD 9.5) months. Among participants with SPPB scores of 3-7, mobility disability occurred in 283/605 (46.8%) assigned to the multicomponent intervention and 316/600 (52.7%) controls (hazard ratio 0.78, 95% confidence interval 0.67 to 0.92; P=0.005). Persistent mobility disability occurred in 127/605 (21.0%) participants assigned to the multicomponent intervention and 150/600 (25.0%) controls (0.79, 0.62 to 1.01; P=0.06). The between group difference in SPPB score was 0.8 points (95% confidence interval 0.5 to 1.1 points; PConclusionsA multicomponent intervention was associated with a reduction in the incidence of mobility disability in older adults with physical frailty and sarcopenia and SPPB scores of 3-7. Physical frailty and sarcopenia may be targeted to preserve mobility in vulnerable older people.Trial registrationClinicalTrials.gov NCT02582138.

Background Low-grade chronic inflammation, characterized by elevations in plasma Interleukin-6 (IL-6), is an independent risk factor of impaired mobility in older persons. Angiotensin receptor blockers and omega-3 polyunsaturated fatty acids (ω-3) may reduce IL-6 and may potentially improve physical function. To assess the main effects of the angiotensin receptor blocker losartan and ω-3 as fish oil on IL-6 and 400 m walking speed, we conducted the ENRGISE Pilot multicenter randomized clinical trial. Methods The ENRGISE Pilot enrolled participants between April 2016 and June 2017, who participated for 12 months. Participants were aged ≥70 years with mobility impairment, had IL-6 between 2.5 and 30 pg/mL, and were able to walk 400 m at baseline. Participants were randomized in three strata 2 × 2 factorial to: (i) losartan 50–100 mg/d or placebo (n = 43), (ii) fish oil 1,400–2,800 mg/d or placebo (n = 180), and (iii) with both (n = 66). Results Two hundred eighty-nine participants were randomized (mean age 78.3 years, 47.4% women, 17.0% black). There was no effect of losartan (difference of means = −0.065 ± 0.116 [SE], 95% confidence interval [CI]: −0.293–0.163, p = .58) or fish oil (−0.020 ± 0.077, 95% CI: −0.171–0.132, p = .80) on the log of IL-6. Similarly, there was no effect of losartan (−0.025 ± 0.026, 95% CI: −0.076–0.026, p = .34) or fish oil (0.010 ± 0.017, 95% CI: −0.025–0.044, p = .58) on walking speed (m/s). Conclusions These results do not support the use of these interventions to prevent mobility loss in older adults at risk of disability with low-grade chronic inflammation. Registration Clinicaltrials.gov NCT02676466.

OBJECTIVES To evaluate the effect of hospitalizations on patterns of sedentary and physical activity time in mobility‐limited older adults randomized to structured physical activity or health education. DESIGN Secondary analysis of investigator‐blinded, parallel‐group, randomized trial conducted at 8 U.S. centers between February 2010 and December 2013. PARTICIPANTS Sedentary men and women aged 70 to 89 at baseline who wore a hip‐fitted accelerometer 7 consecutive days at baseline and 6, 12, and 24 months after randomization (N=1,341). MEASUREMENTS Participants were randomized to a physical activity (PA; n = 669) intervention that included aerobic, resistance, and flexibility training or to a health education (HE; n = 672) intervention that consisted of workshops on older adult health and light upper‐extremity stretching. Accelerometer patterns were characterized as bouts of sedentary (.41). PA participants had less sedentary time in bouts of less than 30 minutes than HE participants (−8 to −10 min/d) and more total activity (+3 to +6 min/d), although hospital‐related changes were similar between the intervention groups (interaction effect p >.26). CONCLUSION Participating in a PA intervention before hospitalization had expected benefits, but participants remained susceptible to hospitalization's detrimental effects on their daily activity levels. There was no evidence of better activity recovery after hospitalization. J Am Geriatr Soc 67:261–268, 2019.