Lifestyle Interventions And Independence For Elders Research Articles

Older adults with clinically relevant depressive symptoms have equal mobility benefit from a chronic physical activity intervention

Approximately 18% of older adults experience mild-to-severe depressive symptoms in the U.S., which in turn can negatively affect their physical and cognitive health. It is widely acknowledged that physical activity has a positive impact on mood and depression and is highly recommended for symptom management across all ages. Little is known, however, about whether elevated depressive symptoms interfere with the potential benefits of chronic exercise on physical outcomes such as mobility improvements in older adults. In this secondary data analysis of the Lifestyle Interventions and Independence for Elders (LIFE) study, we analyzed data from 1545 older adults (mean age = 78.8, 66.7% female) randomized to either a physical activity or health education intervention with an average of 2.2 years of follow-up. We evaluated whether the presence of clinically relevant depressive symptoms (defined as a rescaled score of ≥16 on the Center for Epidemiological Studies-Depression [CES-D]-11 scale) moderated the effect of a chronic physical activity intervention on incident major mobility disability (MMD), objectively measured as the ability to walk 400 m and assessed every 6 months. There were significant main effects of both the physical activity intervention (p = 0.018) and clinically relevant depression (p < 0.001) on incident MMD, but we found no evidence of moderation by depression status (interaction p-value = 0.989). Our findings suggest older adults with clinically relevant depressive symptoms derive similar benefits from participating in a comprehensive physical activity intervention in terms of reduced risk of mobility disability. These results support the inclusion of older adults with depressive symptoms in behavior-based clinical trials.

TESTING THE MODERATING EFFECTS OF DEPRESSIVE SYMPTOMS ON A PHYSICAL ACTIVITY INTERVENTION

Abstract Depressive symptoms affect the physical and cognitive health of approximately 20% of older adults. These symptoms have strong, bidirectional ties with physical activity levels and mobility disability. Physical activity has a positive impact on mood and depression and is highly recommended for symptom management across all ages. However, it’s unclear whether elevated depressive symptoms interfere with potential benefits that physical activity has on other health outcomes like mobility loss. The Lifestyle Interventions and Independence for Elders (LIFE) Study randomized over 1,500 older adults (aged 70+) to either a physical activity (intervention) or successful aging (control) program with an average of 2.2 years of follow-up. Our analysis used Cox proportional hazards models to evaluate whether elevated depressive symptoms (measured using the Center for Epidemiological Studies-Depression (CESD)-11 scale with a cutoff score of 16/22 points) moderated the relationship between intervention status and the primary outcome (incident major mobility disability, objectively measured as the ability to walk 400 meters). In a secondary analysis of 1,534 older adults (Mage = 78.8, 66.7% female), we confirmed significant main effects of both the physical activity intervention and elevated depressive symptoms on incident major mobility disability but found no evidence of moderation (interaction p-value=0.989). Results indicate that the benefits of the intervention were comparable between those with and without significant depressive symptoms at baseline, supporting the inclusion of individuals with depression in clinical trials. In addition to potential symptom relief, promoting physical activity in older adults with depression is important for protecting against mobility loss.

Effect of change of interleukin-6 over time on gait speed response: Results from the lifestyle interventions and independence for elders study

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.

Association between Pneumonia, Fracture, Stroke, Heart Attack and Other Hospitalizations with Changes in Mobility Disability and Gait Speed in Older Adults

Pathophysiological changes after acute hospitalizations may influence physical functioning in older adults, which can lead to disability and loss of independence. This study evaluated the association between pneumonia, fracture, heart attack, stroke, and other hospitalizations with major mobility disability (MMD) and gait speed. This was a secondary analysis of the Lifestyle Interventions and Independence for Elders (LIFE) Study, which was conducted across eight sites during 2010–2013 with longitudinal follow-up for 1635 individuals over an average of 2.6 years. Participants included adults ≥70 years old with pre-existing mobility limitations randomized to a physical activity intervention or a health education control arm. Hospitalizations were recorded via self-report and adjudicated by medical reviewers. MMD was measured by the inability to complete a 400 m walk test, or other proxies, as a binary outcome. Gait speed was recorded during the walk test in meters per second (m/s) and measured on a linear scale. Mixed-effects repeated measures regression adjusted for baseline demographics, comorbid conditions, and frailty. Among the 1635 participants, there were 1458 hospitalizations, which included 80 (5.5% of all hospitalizations) cases of pneumonia, 92 (6.3%) hospitalized fractures, 87 (6.0%) heart attacks, and 61 (4.2%) strokes. In the short-term measurement period immediately following hospitalization (1 day to 6 months), stroke (OR = 3.98 (3.41–4.54)) had the strongest association with MMD followed by fracture (OR = 3.03 (2.54–3.52)), pneumonia (OR = 2.76 (2.23–3.30)), and heart attack (OR = 2.03 (1.52–2.53)). Associations with long-term (6–12 months after) MMD were decreased or not significant for all causes. Pneumonia, fracture, stroke, and other hospitalizations were associated with short-term relative gait speed changes between −4.8% up to −19.5%, and only fracture was associated with long-term changes. Hospitalizations for pneumonia, heart attack, stroke, and fractures were associated with short-term decreases in mobility in older adults. Older adults may be at risk for decreased mobility and disability following acute hospitalizations, with the magnitude determined by the cause of the precipitating event.

Metabolic syndrome and the benefit of a physical activity intervention on lower-extremity function: Results from a randomized clinical trial

In older adults, increases in physical activity may prevent decline in lower-extremity function, but whether the benefit differs according to metabolic syndrome (MetS) status is uncertain. We aim to investigate whether structured physical activity is associated with less decline in lower-extremity function among older adults with versus without MetS. We used data from the multicenter Lifestyle Interventions and Independence for Elders (LIFE) study to analyze 1535 sedentary functionally-vulnerable women and men, aged 70 to 89years old, assessed every 6months (February 2010-December 2013) for an average of 2.7years. Participants were randomized to a structured, moderate-intensity physical activity intervention (PA; n=766) or health education program (HE; n=769). MetS was defined according to the 2009 multi-agency harmonized criteria. Lower-extremity function was assessed by 400-m walking speed and the Short Physical Performance Battery (SPPB) score. 763 (49.7%) participants met criteria for MetS at baseline. Relative to HE, PA was associated with faster 400-m walking speed among participants with MetS (P<0.001) but not among those without MetS (P=0.91), although the test for statistical interaction was marginally non-significant (P=0.07). In contrast, no benefit of PA versus HE was observed on the SPPB score in either MetS subgroup. Among older adults at high risk for mobility disability, moderate-intensity physical activity conveys significant benefits in 400-m walking speed but not SPPB in those with, but not without, MetS. The LIFE physical activity program may be an effective strategy for maintaining or improving walking speed among vulnerable older adults with MetS. clinicaltrials.gov Identifier: NCT01072500.

Effect of Inpatient and Outpatient Pneumonia on Mobility Disability, Gait Speed, and Physical Activity in Older Adults.

Pathophysiological changes caused by pneumonia may influence physical functioning in older adults. This study was a secondary analysis of the Lifestyle Interventions and Independence for Elders (LIFE) Study. The LIFE Study included 1635 individuals over an average follow-up of 2.6 years at eight clinical sites during 2010–2013. Adults ≥70 years-old with mobility limitations (Short Physical Performance Battery score ≤9) were randomized to a physical activity (exercise) intervention or health education control arm. This analysis evaluated the association between pneumonia events and major mobility disability (MMD), gait speed, and physical activity levels. Pneumonia events, classified as inpatient or outpatient, were assessed by self-report during longitudinal follow-up. MMD was measured by the inability to complete a 400-m walk test, or other proxies, as a binary outcome and separately analyzed as “short-term” and “long-term” MMD. Short-term MMD was defined as MMD occurring in the assessment period immediately following (between 1-day to 6-months after) a pneumonia event and long-term was in the following assessment period (6 to 12 months after the event). Short- and long-term gait speed was similarly recorded during the walk test in meters per second (m/s) and measured on a linear scale. Physical activity levels were captured via accelerometry and shown visually. Mixed-effects repeated measures regression adjusted for intervention assignment, baseline demographics, comorbid conditions, and frailty. Among the 1635 participants, n = 174 (10.7%) had a pneumonia event of which 80 (46% of events) were hospitalized. Those with pneumonia during follow-up had higher baseline medication use, prior hospitalizations, and higher prevalence of lung disorders but similar baseline functioning. Pneumonia hospitalization was associated with a 4-fold increase [OR = 4.1 (3.2–5.0)] and outpatient events were associated with a 2-fold increase [OR = 2.6 (2.1–3.1)] in the odds of short-term MMD. Pneumonia hospitalizations, but not outpatient events, were associated with a nearly 10% decrement in short-term gait speed. Pneumonia events were not associated with either long-term MMD or gait speed outcomes. Physical activity levels decreased from baseline immediately following the pneumonia episode (10–30% reductions) and returned to baseline after 6 months. These results emphasize the importance of managing pneumonia risk factors to prevent disease in order to maintain physical independence and activity in older adults.

1469. Effect of pneumonia and pneumonia hospitalization episodes on mobility in older adults: results from the Lifestyle Interventions and Independence for Elders (LIFE) Study

BackgroundMobility is a cornerstone of healthy aging. Pneumonia may impact mobility through damage to physiological systems as well as increased inflammation, which has been associated with reduced physical functioning. The objective of this study was to assess the impact of pneumonia on objectively measured physical functioning in a sample of older adults.MethodsThis was a post-hoc analysis of the Lifestyle Interventions and Independence for Elders (LIFE) Study provided by the National Institute on Aging’s AgingResearchBiobank. Participants with pre-existing mobility concerns aged 70-89 years were randomized to physical activity or health education interventions. Outcomes included the ability to complete a 400-meter walk and gait speed (meters/second, m/s) and were assessed every 6 months from baseline up to 42 months. New health events were assessed at each visit including overall pneumonia events and pneumonia hospitalizations. Repeated measures regression models evaluated the ability to walk 400-meters and gait speed as separate outcomes controlling for age, sex, race, education, past medical history, the occurrence of other health events, and a cumulative deficit frailty index.ResultsThere were 1,635 LIFE Study participants with N=9,872 follow-up measures during the study period. Among these, 174 (10.6%) had a pneumonia event which included 96 hospitalization events. Those with pneumonia events during follow-up were mostly similar to those without pneumonia events at baseline, except for higher prevalence of past hospitalizations and respiratory problems. Any pneumonia event was associated with an adjusted mean gait speed of 0.67 (0.63-0.71) m/s vs. 0.70 (0.66-0.73) m/s in those without pneumonia and 0.60 (0.55-0.64) in those with pneumonia hospitalization. Similarly, pneumonia events were associated with 84% [odds ratio = 1.84 (1.45-2.23)] and pneumonia hospitalizations with 200% [odds ratio = 3.00 (2.48-3.52)] increases in the odds of not being able to walk 400-meters compared to those without pneumonia events.ConclusionPneumonia-related health events were associated with subsequent reduced mobility measured by 400-meter walk tests and gait speed. Preventing pneumonia may be an important component of maintaining physical functioning in older adults.DisclosuresJoshua Brown, PharmD, PhD, Pfizer, Inc (Consultant, Grant/Research Support) Reiko Sato, PhD, Pfizer, Inc (Employee, Shareholder) John Morley, MD, Pfizer, Inc (Consultant)

Machine Learning in Aging: An Example of Developing Prediction Models for Serious Fall Injury in Older Adults

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 understanding the complex algorithms behind 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. 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. 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 in 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). Machine learning methods may offer improved performance compared to traditional models 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.

Association between a Deficit Accumulation Frailty Index and Mobility Outcomes in Older Adults: Secondary Analysis of the Lifestyle Interventions and Independence for Elders (LIFE) Study.

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’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 ± 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 1–5, respectively. Each 1-unit increase in the frailty index increased the hazard of MMD by 4% (2–5%), 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.

Machine Learning in Aging: An Example of Developing Prediction Models for Serious Fall Injury in Older Adults.

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. 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. 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). 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.

Three-Year, Postintervention, Follow-up Comparison of Health Care Resource Utilization and Costs in the Lifestyle Interventions and Independence for Elders (LIFE) Study.

The Lifestyle Interventions and Independence for Elders (LIFE) Study physical activity (PA) intervention was found to be cost-effective compared to health education (HE). However, long-term effects postintervention are unknown. This was a secondary analysis of LIFE Study data linked to Medicare claims data (2014-2016). Participants were linked via Social Security Numbers to Medicare claims data. Utilization and cost variables were analyzed using generalized linear models with negative binomial and Tweedie distributions. Unadjusted means and 95% confidence intervals were compared by year and overall stratified. Each model compared PA versus HE and adjusted for other baseline characteristics and stratified by study site. Additional models were stratified by baseline physical functioning assessment scores. Of the 1,635 LIFE Study participants, 804 (53.5%) were linked to Medicare claims with an average of 33 months of follow-up time during the 3-year data linkage period. Mean outpatient (6.6 vs 6.8), inpatient (0.40 vs 0.40), and other utilization metrics were similar between PA and HE groups. Costs were also similar for each group and each type of service, for example, outpatient: $2,070 versus $2,093 and inpatient: $4,704 versus $4,792. Regression results indicated no statistically significant differences between PA and HE groups. While the LIFE Study demonstrated that PA reduced mobility disability in older adults and was cost-effective, it did not appear to affect long-term health care utilization costs posttrial. These findings suggest that it remains challenging to affect long-term health care costs using PA interventions effects.

Relationships Between Profiles of Physical Activity and Major Mobility Disability in the LIFE Study.

To examine the relationship between time spent in light physical activity (LPA) and in moderate to vigorous physical activity (MVPA) and the pattern of accumulation on the risk for major mobility disability (MMD) in a large multicenter study of physical activity (PA) and aging, the Lifestyle Interventions and Independence for Elders (LIFE) study. Data were collected from individuals randomized to a PA intervention as part of the LIFE study, an eight-center single-blind randomized clinical trial conducted between February 2010 and December 2013. Lifestyle Interventions and Independence for Elders Study PARTICIPANTS: Older adult participants (78.4 years; N = 507) at risk for MMD. All older adults included in these analyses were randomized to a structured PA intervention that included two center-based plus three to four home-based exercise sessions per week with a primary goal of walking for 150 minutes weekly. Participants attended the intervention for 2.5 years on average. MMD was defined as the inability to complete a 400-m walk within 15 minutes and without assistance. Physical function was assessed via the Short Physical Performance Battery (SPPB). Actigraph accelerometers were used to quantify amount and variability in LPA and MVPA. In an adjusted Cox proportional hazards regression, we identified a significant interaction (P = .017) between SPPB score and LPA amount and variability such that more LPA was associated with a reduced risk for MMD among those with higher initial function, as was lower variability (eg, via distributing LPA across the day). The SPPB × MVPA interaction was significant (P = .04), such that more MVPA was associated with lower MMD risk among those with lower function. Finally, greater MVPA variability was associated with lower risk for MMD. A prescription of PA for older adults should account for key factors such as physical function and emphasize both amount and pattern of accumulation of PA from across the intensity continuum. J Am Geriatr Soc 68:1476-1483, 2020.

Impact and Lessons From the Lifestyle Interventions and Independence for Elders (LIFE) Clinical Trials of Physical Activity to Prevent Mobility Disability.

BACKGROUNDWalking independently is basic to human functioning. The Lifestyle Interventions and Independence for Elders (LIFE) studies were developed to assess whether initiating physical activity could prevent major mobility disability (MMD) in sedentary older adults.METHODSWe review the development and selected findings of the LIFE studies from 2000 through 2019, including the planning phase, the LIFE‐Pilot Study, and the LIFE Study.RESULTSThe planning phase and the LIFE‐Pilot provided key information for the successful implementation of the LIFE Study. The LIFE Study, involving 1635 participants randomized at eight sites throughout the United States, showed that compared with health education, the physical activity program reduced the risk of the primary outcome of MMD (inability to walk 400 m: hazard ratio = 0.82; 95% confidence interval = 0.69‐0.98; P = .03), and that the intervention was cost‐effective. There were no significant effects on cognitive outcomes, cardiovascular events, or serious fall injuries. In addition, the LIFE studies provided relevant findings on a broad range of other outcomes, including health, frailty, behavioral outcomes, biomarkers, and imaging. To date, the LIFE studies have generated a legacy of 109 peer‐reviewed publications, 19 ancillary studies, and 38 independently funded grants and clinical trials, and advanced the development of 59 early career scientists. Data and biological samples of the LIFE Study are now publicly available from a repository sponsored by the National Institute on Aging (https://urldefense.proofpoint.com/v2/url?u=https-3A__agingresearchbiobank.nia.nih.gov&d=DwMFAg&c=pZJPUDQ3SB9JplYbifm4nt2lEVG5pWx2KikqINpWlZM&r=ZX4a6hcfLVk9tpCPmkSujQ&m=iTPARxl_LBOimJoAcWK4efKQBWBHszm-g4mUN_o5-bc&s=SrlCccrcYCFSyWnnprcB3rJXT3W3FkGkW0XmdJITNhE&e=).CONCLUSIONSThe LIFE studies generated a wealth of important scientific findings and accelerated research in geriatrics and gerontology, benefiting the research community, trainees, clinicians, policy makers, and the general public. J Am Geriatr Soc 68:872–881, 2020

Impact of Baseline Fatigue on a Physical Activity Intervention to Prevent Mobility Disability.

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. Prospective cohort of individuals aged 65 years or older undergoing structured PA intervention or health education (HE) for a mean of 2.6 years. 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. Study participants (N = 1591) at baseline were 78.9 ± 5.2 years of age, with low PA and at risk for mobility impairment. 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. 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). 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.

PERIPHERAL ARTERIAL DISEASE AND SEDENTARY TIME IN OLDER ADULTS

Peripheral artery disease (PAD) is associated with increased rates of physical disability in older adults, yet few interventions exist to reduce this risk. Intermittent claudication, exertional calf symptoms that resolve within 10 minutes of rest, is the classic symptom for PAD, but many people with PAD are absent of these symptoms. Ankle brachial index (ABI) is a non-invasive measure that identifies the presence and severity of lower extremity arterial obstruction due to atherosclerosis. We studied whether abnormal ABI is associated with increased time spent in sedentary behavior in a large sample of community-dwelling older men and women (70-89 years) enrolled in the Lifestyle Interventions and Independence for Elders (LIFE) study. Older adults underwent an ABI test and then wore a tri-axial accelerometer on the hip for up to seven days. Total accumulated sedentary time and sedentary time spent in bout lengths of 10minutes or more, 30 minutes or more, and 60 minutes or more were calculated. ABI values, divided into PAD (<.90, n=156) and non-PAD (0.90 - 1.40, n=960), were evaluated in covariate-adjusted regression models adjusting for age, body mass index, comorbidity presence, gender and smoking. Older adults with PAD had significantly higher total accumulated time spent in sedentary behavior than those without PAD (13.1 minutes per day, p<0.02). No associations were found with longer bout lengths of sedentary time. These results suggest that older adults with PAD accumulate more time in shorter bouts of sedentary behavior. Future interventions may consider targeting short sedentary bout-lengths for reducing PAD symptoms.

Cognitive Function as a Predictor of Major Mobility Disability in Older Adults: Results From the LIFE Study.

Background and ObjectivesMany cross-sectional studies have confirmed a link between gait speed and cognitive function. However, it is unknown whether cognitive function plays a role in the onset of major mobility disability (MMD) and if the effects are independent of physical function. This study examined cognitive and physical function as predictors of MMD across an average of 2.6 years of follow-up in community-dwelling older adults with compromised mobility.Research Design and MethodData were collected from 1,635 participants in the Lifestyle Interventions and Independence for Elders (LIFE) study ages 70–89 years free of MMD at baseline. MMD was assessed every 6 months and defined as the inability to walk 400 m in ≤15 min without assistance or sitting. Cognitive function was assessed at baseline, 18 months, and 24 months using a cognitive battery categorized into four domains: global cognitive function, processing speed, verbal memory, and executive function.ResultsAcross the study duration of 2.6 years, 536 participants (32.8%) developed MMD. Cox Proportional Hazard models indicated a protective relationship for higher baseline processing speed (Hazard Ratio [HR] per standard deviation: 0.86, p = .006), executive function (HR: 0.86, p = .002), and global cognition (HR: 0.85, p = .001) on incidence of MMD adjusted for demographics, intervention, and comorbidities. Results were not significant after adjustment for gait speed. In adjusted longitudinal models, a positive change in processing speed was significantly associated with reduced risk of MMD (HR: 0.52, p < .001) while other domains were not.Discussion and ImplicationsIn the LIFE study, processing speed at baseline and follow-up was a significant predictor of subsequent MMD although the observed association may be explained by physical function as reflected in gait speed. More studies are needed to understand how cognitive function, alone and in combination with physical function, influences risk of MMD.

Effect of 24-month physical activity on cognitive frailty and the role of inflammation: the LIFE randomized clinical trial

BackgroundWhether physical activity can reduce cognitive frailty—a relatively new “compound” phenotype proposed in 2013—and whether the effect of physical activity differs based on levels of inflammation are unknown. Therefore, this study aimed to evaluate the effect of physical activity on cognitive frailty and whether baseline interleukin-6 (IL-6) levels modified this effect.MethodsWe used data from the Lifestyle Interventions and Independence for Elders (LIFE) Study, a multicenter, single-blinded randomized trial conducted at eight US field centers between February 2010 and December 2013. The main outcome was cognitive frailty at 24 months, expressed as an ordinal variable based on the six combinations of its two components: frailty (non-frail, pre-frail, and frail) and mild cognitive impairment (yes, no). Frailty and cognition were assessed by the Study of Osteoporotic Fractures (SOF) index and the Modified Mini-Mental State Examination (3MSE) scale, respectively. Plasma IL-6 was measured at baseline. Of the 1635 original randomized sedentary participants (70–89 years), this study included 1298 participants with data on both cognitive frailty and IL-6 assessments at baseline.ResultsAfter adjusting for field center, sex, and baseline levels of cognitive frailty, the ordinal logistic regression model revealed that participants in the physical activity group had 21% lower odds (odds ratio, 0.79; 95% confidence interval, 0.64–0.98) of worsening cognitive frailty over 24 months than those in the health education group. The effect of physical activity on cognitive frailty did not differ according to baseline IL-6 levels (P for interaction = 0.919). The results did not change after additional adjustment for IL-6 subgroups and the inverse probability of remaining in the study. Comparable results were observed according to age, sex, ethnicity/race, and short physical performance battery score (P for interaction = 0.835, 0.536, 0.934, and 0.458, respectively).ConclusionsA 24-month structured, moderate-intensity physical activity program reduced cognitive frailty compared with a health education program in sedentary older persons, and this beneficial effect did not differ according to baseline levels of inflammatory biomarker IL-6. These findings suggest that the new cognitive frailty construct is modifiable and highlight the potential of targeting cognitive frailty for promoting healthy aging.Trial registrationClinicaltrials.gov, NCT01072500

Meta-analysis identifies mitochondrial DNA sequence variants associated with walking speed.

Declines in walking speed are associated with a variety of poor health outcomes including disability, comorbidity, and mortality. While genetic factors are putative contributors to variability in walking, few genetic loci have been identified for this trait. We examined the role of mitochondrial genomic variation on walking speed by sequencing the entire mitochondrial DNA (mtDNA). Data were meta-analyzed from 1758 Lifestyle Interventions and Independence for Elders (LIFE) Study and replication data from 730 Health, Aging, and Body Composition (HABC) Study participants with baseline walking speed information. Participants were 69+ years old of diverse racial backgrounds (African, European, and other race/ethnic groups) and had a wide range of mean walking speeds [4-6m (0.78-1.09m/s) and 400m (0.83-1.24m/s)]. Meta-analysis across studies and racial groups showed that m.12705C>T, ND5 variant was significantly associated (p < 0.0001) with walking speed at both short and long distances. Replication and meta-analysis also identified statistically significant walking speed associations (p < 0.0001) between the m.5460.G>A, ND2 and m.309C>CT, HV2 variants at short and long distances, respectively. All results remained statistically significant after multiple comparisons adjustment for 499 mtDNA variants. The m.12705C>T variant can be traced to the beginnings of human global migration and that cells carrying this variant display altered tRNA expression. Significant pooled effects related to stopping during the long-distance walk test were observed across OXPHOS complexes I (p = 0.0017) and III (p = 0.0048). These results suggest that mtDNA-encoded variants are associated with differences in walking speed among older adults, potentially identifying those at risk of developing mobility impairments.

Self-Reported Physical Function As a Predictor of Hospitalization in the Lifestyle Interventions and Independence for Elders Study.

To explore whether baseline scores on the Mobility Assessment Tool-short form (MAT-sf), a brief, animated, computer-based means of assessing mobility that predicts mobility disability, are associated with number of hospitalizations and time to first hospitalization over a median follow-up of 2.7 years. Post hoc analysis of prospectively gathered data from the Lifestyle Interventions and Independence for Elders (LIFE) Study, a randomized clinical trial of lifestyle interventions to preserve mobility in older adults. Eight U.S. academic medical centers. Of 1,635 sedentary community-dwelling older adults enrolled in LIFE, 1,574 completed baseline physical function screening including the MAT-sf, with baseline scores ranging from 30.2 (low function) to 69.8 (high function) on a scale from 30 to 80. Number of hospitalizations and time to first hospitalization, adjusted for age, sex, race, living alone, clinical site, baseline comorbidities, number of prescription medications, and cognition. Of the 1,557 participants with data regarding hospitalization status, 726 (47%) had at least 1 hospitalization; 78% of these had 1 or 2 hospitalizations. For every 10-point lower MAT-sf score, the rate of all hospitalizations was 19% higher in those with lower scores (adjusted rate ratio=1.20, 95% confidence interval (CI)=1.08-1.32, p<.001). Lower baseline MAT-sf scores were also associated with greater risk of first hospitalization (adjusted hazard ratio=1.20, 95% CI=1.09-1.32, p<.01, per 10-point lower MAT-sf score). Low MAT-sf scores identify older adults at risk of hospitalization; further study is needed to test interventions to reduce hospitalizations in these individuals.

Mitochondrial DNA Sequence Variants Associated With Blood Pressure Among 2 Cohorts of Older Adults.

BackgroundAge‐related changes in blood pressure are associated with a variety of poor health outcomes. Genetic factors are proposed contributors to age‐related increases in blood pressure, but few genetic loci have been identified. We examined the role of mitochondrial genomic variation in blood pressure by sequencing the mitochondrial genome.Methods and ResultsMitochondrial DNA (mtDNA) data from 1755 participants from the LIFE (Lifestyle Interventions and Independence for Elders) studies and 788 participants from the Health ABC (Health, Aging, and Body Composition) study were evaluated using replication analysis followed by meta‐analysis. Participants were aged ≥69 years, of diverse racial backgrounds, and assessed for systolic blood pressure (SBP), diastolic blood pressure, and mean arterial pressure. After meta‐analysis across the LIFE and Health ABC studies, statistically significant associations of mtDNA variants with higher SBP (m.3197T>C, 16S rRNA; P=0.0005) and mean arterial pressure (m.15924A>G, t‐RNA‐thr; P=0.004) were identified in white participants. Among black participants, statistically significant associations with higher SBP (m.93A>G, HVII; m.16183A>C, HVI; both P=0.0001) and mean arterial pressure (m.16172T>C, HVI; m.16183A>C, HVI; m.16189T>C, HVI; m.12705C>T; all P's<0.0004) were observed. Significant pooled effects on SBP were observed across all transfer RNA regions (P=0.0056) in white participants. The individual and aggregate variant results are statistically significant after multiple comparisons adjustment for the number of mtDNA variants and mitochondrial regions examined.ConclusionsThese results suggest that mtDNA‐encoded variants are associated with variation in SBP and mean arterial pressure among older adults. These results may help identify mitochondrial activities to explain differences in blood pressure in older adults and generate new hypotheses surrounding mtDNA variation and the regulation of blood pressure.Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifiers: NCT01072500 and NCT00116194.