Frailty and risk of mortality in older cancer survivors and adults without a cancer history: Evidence from the National Health and Nutrition Examination Survey, 1999-2014.

BACKGROUND: Epidemiologic evidence reporting the role of frailty in survival among older adults with a prior cancer diagnosis is limited. METHODS: 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], 0.10 < FI ≤ 0.21 [prefrail], and FI > 0.21 [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. RESULTS: 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 0.10 < FI ≤ 0.21, and 7.5 per 100 person-years for FI > 0.21) 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 0.10 < FI ≤ 0.21, and 5.4 per 100 person-years for FI > 0.21). The multivariable model suggested a positive association between the FI and all-cause mortality for survivors (aHR for FI > 0.21 vs FI ≤ 0.10, 2.80; 95% CI, 1.73-4.53) and participants without a cancer history (aHR for FI > 0.21 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. CONCLUSIONS: Frailty is associated with a higher risk of death in older cancer survivors and the elderly without a cancer history.

Evaluation of the key prescription sequence symmetry analysis assumption using the calcium channel blocker: Loop diuretic prescribing cascade.

OBJECTIVES: To evaluate the prescription sequence symmetry analysis assumption regarding balance between marker drug (i.e., medication used to treat a drug-induced adverse event) initiation rates before and after initiation of an index drug (i.e., medication that is potentially associated with the drug-induced adverse event) in the absence of prescribing cascades, we used a well-described example of loop diuretic initiation to treat dihydropyridine calcium channel blockers (DH CCB)-induced edema. STUDY DESIGN AND SETTING: The University of Florida Health Integrated Data Repository from June 2011 and July 2018 was used to assess temporal prescribing of DH CCB and loop diuretics within the prescription sequence symmetry analysis framework. Validation of the prescribing cascade was performed via clinical expert chart review. RESULTS: Among patients without heart failure who were initiated on DH CCB, 26 and 64 loop diuretics initiators started within 360 days before versus after DH CCB initiation, respectively, resulting in an adjusted sequence ratio (aSR) of 2.27 (95% CI, 1.44-3.58). Overall, 35 (54.7%) patients were determined to have a prescribing cascade. Removing patients who experienced a prescribing cascade resulted in an aSR of 1.05, 95% CI 0.62-1.78). CONCLUSION: Loop diuretic initiation rates before and after DH CCB initiation for reasons other a prescribing cascade were similar, thus confirming the prescription sequence symmetry analysis assumption.

Are Machine Learning Models on Wrist Accelerometry Robust against Differences in Physical Performance among Older Adults?

Sufficient physical activity (PA) reduces the risk of a myriad of diseases and preserves physical capabilities in later life. While there have been significant achievements in mapping accelerations to real-life movements using machine learning (ML), errors continue to be common, particularly for wrist-worn devices. It remains unknown whether ML models are robust for estimating age-related loss of physical function. In this study, we evaluated the performance of ML models (XGBoost and LASSO) to estimate the hallmark measures of PA in low physical performance (LPP) and high physical performance (HPP) groups. Our models were built to recognize PA types and intensities, identify each individual activity, and estimate energy expenditure (EE) using wrist-worn accelerometer data (33 activities per participant) from a large sample of participants (n = 247, 57% females, aged 60+ years). Results indicated that the ML models were accurate in recognizing PA by type and intensity while also estimating EE accurately. However, the models built to recognize individual activities were less robust. Across all tasks, XGBoost outperformed LASSO. XGBoost obtained F1-Scores for sedentary (0.932 ± 0.005), locomotion (0.946 ± 0.003), lifestyle (0.927 ± 0.006), and strength flexibility exercise (0.915 ± 0.017) activity type recognition tasks. The F1-Scores for recognizing low, light, and moderate activity intensity were (0.932 ± 0.005), (0.840 ± 0.004), and (0.869 ± 0.005), respectively. The root mean square error for EE estimation was 0.836 ± 0.059 METs. There was no evidence showing that splitting the participants into the LPP and HPP groups improved the models' performance on estimating the hallmark measures of physical activities. In conclusion, using features derived from wrist-worn accelerometer data, machine learning models can accurately recognize PA types and intensities and estimate EE for older adults with high and low physical function.

Sustained physical activity in peripheral artery disease: Associations with disease severity, functional performance, health-related quality of life, and subsequent serious adverse events in the LITE randomized clinical trial.

This study investigated cross-sectional associations of peripheral artery disease (PAD) severity (defined by the ankle-brachial index (ABI)) and amounts of daily sustained physical activity (PA) (defined as > 100 activity counts per minute lasting 5 consecutive minutes or more). This study also investigated associations of amounts of daily sustained PA with 6-minute walk (6MW) distance and the Short Form-36 physical functioning domain (SF-36 PF) score in cross-sectional analyses and with serious adverse events (SAEs) in longitudinal analyses of people with PAD. PA was measured continuously for 10 days using a tri-axial accelerometer at baseline in 277 participants with PAD randomized to the LITE clinical trial. In regression analyses, each 0.15 lower ABI value was associated with a 5.67% decrease in the number of daily bouts of sustained PA (95% CI: 3.85-6.54; p < 0.001). Every additional bout of sustained PA per day was associated with a 4.56-meter greater 6MW distance (95% CI: 2.67-6.46; p < 0.0001), and a 0.81-point improvement in SF-36 PF score (95% CI: 0.34-1.28; p < 0.001). Participants with values of daily bouts of sustained PA below the median had higher rates of SAEs during follow-up, compared to participants above the median (41% vs 24%; p = 0.002). In conclusion, among participants with PAD, lower ABI values were associated with fewer bouts of daily sustained PA. A greater number of bouts of daily sustained PA were associated with better 6MW performance and SF-36 PF score, and, in longitudinal analyses, lower rates of SAEs. Clinicaltrials.gov ID: NCT02538900.

Study Protocol Modeling Evoked Pain in Older African Americans With Knee Osteoarthritis.

BACKGROUND: African American (AA) older adults with knee osteoarthritis experience more severe chronic pain and advanced physical disability. One of the most prominent stimuli that provokes knee pain is movement. Research suggests that, compared to Whites, AAs report significantly higher movement-evoked pain (MEP) in the knee. However, little is known about the biopsychosocial-behavioral mechanisms underlying MEP. OBJECTIVES: The aim of the study was to present a study protocol to (a) characterize the biopsychosocial-behavioral mechanisms that predict MEP in AAs with knee osteoarthritis and (b) develop a targeted, mechanism-based self-management intervention to reduce MEP and maximize movement. METHODS: An observational, mixed-methods cohort study will enroll 90 AA/Black adults (ages 55-90 years) to understand intraindividual and interindividual effects on MEP. Participants will complete assessments of MEP, function and gait, biopsychosocial-behavioral questionnaires, quantitative sensory testing, and 7-day ecological momentary assessments of pain and related symptoms. For the qualitative phase, focus groups will be conducted to co-construct a mechanism-based pain self-management intervention. RESULTS: We will develop phenotypes of MEP based on biopsychosocial-behavioral predictors and correlate measures of MEP with function. Our central hypothesis is that higher levels of MEP will predict lower self-reported function and poorer performance on functional tasks and that multiple biopsychosocial and behavioral factors will be associated with MEP and function. Predictors may serve as risk or protective factors for MEP and physical function. In targeting the biopsychosocial-behavioral mechanisms of MEP, we anticipate that older AAs may request that intervention components include culturally tailored self-management education, movement/physical activity training, treatment decision-making skills, coaching, spirituality, and social/kinship support. CONCLUSION: Osteoarthritis is now the single most common cause of disability, mobility limitations, and persistent pain in older adults-especially AA older adults. To our knowledge, this will be the first study to systematically phenotype MEP in an older racial minority population with knee osteoarthritis and will be relevant for reducing knee pain and improving function.

Age Differences in Estimating Physical Activity by Wrist Accelerometry Using Machine Learning.

Accelerometer-based fitness trackers and smartwatches are proliferating with incessant attention towards health tracking. Despite their growing popularity, accurately measuring hallmark measures of physical activities has yet to be accomplished in adults of all ages. In this work, we evaluated the performance of four machine learning models: decision tree, random forest, extreme gradient boosting (XGBoost) and least absolute shrinkage and selection operator (LASSO), to estimate the hallmark measures of physical activities in young (20-50 years), middle-aged (50-70 years], and older adults (70-89 years]. Our models were built to recognize physical activity types, recognize physical activity intensities, estimate energy expenditure (EE) and recognize individual physical activities using wrist-worn tri-axial accelerometer data (33 activities per participant) from a large sample of participants (n = 253, 62% women, aged 20-89 years old). Results showed that the machine learning models were quite accurate at recognizing physical activity type and intensity and estimating energy expenditure. However, models performed less optimally when recognizing individual physical activities. F1-Scores derived from XGBoost's models were high for sedentary (0.955-0.973), locomotion (0.942-0.964) and lifestyle (0.913-0.949) activity types with no apparent difference across age groups. Low (0.919-0.947), light (0.813-0.828) and moderate (0.846-0.875) physical activity intensities were also recognized accurately. The root mean square error range for EE was approximately 1 equivalent of resting EE [0.835-1.009 METs]. Generally, random forest and XGBoost models outperformed other models. In conclusion, machine learning models to label physical activity types, activity intensity and energy expenditure are accurate and there are minimal differences in their performance across young, middle-aged and older adults.

Effect of Low-Intensity vs High-Intensity Home-Based Walking Exercise on Walk Distance in Patients With Peripheral Artery Disease: The LITE Randomized Clinical Trial.

Importance: Supervised high-intensity walking exercise that induces ischemic leg symptoms is the first-line therapy for people with lower-extremity peripheral artery disease (PAD), but adherence is poor. Objective: To determine whether low-intensity home-based walking exercise at a comfortable pace significantly improves walking ability in people with PAD vs high-intensity home-based walking exercise that induces ischemic leg symptoms and vs a nonexercise control. Design, Setting, and Participants: Multicenter randomized clinical trial conducted at 4 US centers and including 305 participants. Enrollment occurred between September 25, 2015, and December 11, 2019; final follow-up was October 7, 2020. Interventions: Participants with PAD were randomized to low-intensity walking exercise (n = 116), high-intensity walking exercise (n = 124), or nonexercise control (n = 65) for 12 months. Both exercise groups were asked to walk for exercise in an unsupervised setting 5 times per week for up to 50 minutes per session wearing an accelerometer to document exercise intensity and time. The low-intensity group walked at a pace without ischemic leg symptoms. The high-intensity group walked at a pace eliciting moderate to severe ischemic leg symptoms. Accelerometer data were viewable to a coach who telephoned participants weekly for 12 months and helped them adhere to their prescribed exercise. The nonexercise control group received weekly educational telephone calls for 12 months. Main Outcomes and Measures: The primary outcome was mean change in 6-minute walk distance at 12 months (minimum clinically important difference, 8-20 m). Results: Among 305 randomized patients (mean age, 69.3 [SD, 9.5] years, 146 [47.9%] women, 181 [59.3%] Black patients), 250 (82%) completed 12-month follow-up. The 6-minute walk distance changed from 332.1 m at baseline to 327.5 m at 12-month follow-up in the low-intensity exercise group (within-group mean change, -6.4 m [95% CI, -21.5 to 8.8 m]; P = .34) and from 338.1 m to 371.2 m in the high-intensity exercise group (within-group mean change, 34.5 m [95% CI, 20.1 to 48.9 m]; P < .001) and the mean change for the between-group comparison was -40.9 m (97.5% CI, -61.7 to -20.0 m; P < .001). The 6-minute walk distance changed from 328.1 m at baseline to 317.5 m at 12-month follow-up in the nonexercise control group (within-group mean change, -15.1 m [95% CI, -35.8 to 5.7 m]; P = .10), which was not significantly different from the change in the low-intensity exercise group (between-group mean change, 8.7 m [97.5% CI, -17.0 to 34.4 m]; P = .44). Of 184 serious adverse events, the event rate per participant was 0.64 in the low-intensity group, 0.65 in the high-intensity group, and 0.46 in the nonexercise control group. One serious adverse event in each exercise group was related to study participation. Conclusions and Relevance: Among patients with PAD, low-intensity home-based exercise was significantly less effective than high-intensity home-based exercise and was not significantly different from the nonexercise control for improving 6-minute walk distance. These results do not support the use of low-intensity home-based walking exercise for improving objectively measured walking performance in patients with PAD. Trial Registration: ClinicalTrials.gov Identifier: NCT02538900.

Relative contribution of muscle strength, lean mass, and lower extremity motor function in explaining between-person variance in mobility in older adults.

BACKGROUND: Approximately 35% of individuals > 70 years have mobility limitations. Historically, it was posited lean mass and muscle strength were major contributors to mobility limitations, but recent findings indicate lean mass and muscle strength only moderately explain mobility limitations. One likely reason is that lean mass and muscle strength do not necessarily incorporate measures globally reflective of motor function (defined as the ability to learn, or to demonstrate, the skillful and efficient assumption, maintenance, modification, and control of voluntary postures and movement patterns). In this study we determined the relative contribution of lean mass, muscle strength, and the four square step test, as an index of lower extremity motor function, in explaining between-participant variance in mobility tasks. METHODS: In community-dwelling older adults (N = 89; 67% women; mean 74.9 ± 6.7 years), we quantified grip and leg extension strength, total and regional lean mass, and time to complete the four square step test. Mobility was assessed via 6-min walk gait speed, stair climb power, 5x-chair rise time, and time to complete a complex functional task. Multifactorial linear regression modeling was used to determine the relative contribution (via semi-partial r2) for indices of lean mass, indices of muscle strength, and the four square step test. RESULTS: When aggregated by sex, the four square step test explained 17-34% of the variance for all mobility tasks (p <  0.01). Muscle strength explained ~ 12% and ~ 7% of the variance in 6-min walk gait speed and 5x-chair rise time, respectively (p <  0.02). Lean mass explained 32% and ~ 4% of the variance in stair climb power and complex functional task time, respectively (p <  0.02). When disaggregated by sex, lean mass was a stronger predictor of mobility in men. CONCLUSION: The four square step test is uniquely associated with multiple measures of mobility in older adults, suggesting lower extremity motor function is an important factor for mobility performance. TRIAL REGISTRATION: NCT02505529 -2015/07/22.

Transcutaneous Electrical Stimulation on the Submental Area: The Relations of Biopsychological Factors with Maximum Amplitude Tolerance and Perceived Discomfort Level.

Transcutaneous electrical stimulation (TES) is a frequently used adjunctive modality in dysphagia rehabilitation. Stimulating deeper swallowing muscles requires higher TES amplitude. However, TES amplitude is limited by maximum amplitude tolerance (MAT). Previous studies have reported high interindividual variability regarding MAT and perceived discomfort. This variability might be one of the potential reasons of conflicting outcomes in TES-based swallowing studies. MAT and perceived discomfort are influenced by a variety of biopsychological factors. The influence of these factors related to swallow applications is poorly understood. This study explored the relation of biopsychological factors with MAT and perceived discomfort related to TES in the submental area. A convenience sample of thirty community-dwelling older adults between 60 and 70 years of age provided data for this study. Gender, submental adipose tissue thickness, perceptual pain sensitivity, and pain-coping strategies were evaluated for each subject. Subsequently, MAT and perceived discomfort level were determined using TES on the submental area. Relation of different biopsychological variables with MAT and discomfort level was examined using Pearson and Spearman correlation, and Mann-Whitney U test. Results indicated that neither gender nor adipose thickness was related to MAT and perceived discomfort. Among studied pain-coping strategies, catastrophizing was significantly related to MAT(r = - 0.552, p < .002). Distraction was significantly related to perceived discomfort level (r = - 0.561, p < 0.002). Given the negative impact of pain catastrophizing on MAT and the positive impact of distraction on perceiving discomfort, these coping strategies should be considered as amplitude-limiting and discomfort-moderating factors in TES-based dysphagia rehabilitation.

A smartwatch-based framework for real-time and online assessment and mobility monitoring.

Smartphone and smartwatch technology is changing the transmission and monitoring landscape for patients and research participants to communicate their healthcare information in real time. Flexible, bidirectional and real-time control of communication allows development of a rich set of healthcare applications that can provide interactivity with the participant and adapt dynamically to their changing environment. Additionally, smartwatches have a variety of sensors suitable for collecting physical activity and location data. The combination of all these features makes it possible to transmit the collected data to a remote server, and thus, to monitor physical activity and potentially social activity in real time. As smartwatches exhibit high user acceptability and increasing popularity, they are ideal devices for monitoring activities for extended periods of time to investigate the physical activity patterns in free-living condition and their relationship with the seemingly random occurring illnesses, which have remained a challenge in the current literature. Therefore, the purpose of this study was to develop a smartwatch-based framework for real-time and online assessment and mobility monitoring (ROAMM). The proposed ROAMM framework will include a smartwatch application and server. The smartwatch application will be used to collect and preprocess data. The server will be used to store and retrieve data, remote monitor, and for other administrative purposes. With the integration of sensor-based and user-reported data collection, the ROAMM framework allows for data visualization and summary statistics in real-time.

Effect of Physical Activity on Frailty: Secondary Analysis of a Randomized Controlled Trial.

Background: Limited evidence suggests that physical activity may prevent frailty and associated negative outcomes in older adults. Definitive data from large long-term randomized trials are lacking. Objective: To determine whether a long-term, structured, moderate-intensity physical activity program is associated with a lower risk for frailty and whether frailty status alters the effect of physical activity on the reduction in major mobility disability (MMD) risk. Design: Multicenter, single-blind, randomized trial. Setting: 8 centers in the United States. Participants: 1635 community-dwelling adults, aged 70 to 89 years, with functional limitations. Intervention: A structured, moderate-intensity physical activity program incorporating aerobic, resistance, and flexibility activities or a health education program consisting of workshops and stretching exercises. Measurements: Frailty, as defined by the SOF (Study of Osteoporotic Fractures) index, at baseline and 6, 12, and 24 months, and MMD, defined as the inability to walk 400 m, for up to 3.5 years. Results: Over 24 months of follow-up, the risk for frailty (n = 1623) was not statistically significantly different in the physical activity versus the health education group (adjusted prevalence difference, -0.021 [95% CI, -0.049 to 0.007]). Among the 3 criteria of the SOF index, the physical activity intervention was associated with improvement in the inability to rise from a chair (adjusted prevalence difference, -0.050 [CI, -0.081 to -0.020]). Baseline frailty status did not modify the effect of physical activity on reducing incident MMD (P for interaction = 0.91). Limitation: Frailty status was neither an entry criterion nor a randomization stratum. Conclusion: A structured, moderate-intensity physical activity program was not associated with a reduced risk for frailty over 2 years among sedentary, community-dwelling older adults. The beneficial effect of physical activity on the incidence of MMD did not differ between frail and nonfrail participants. Primary Funding Source: National Institute on Aging, National Institutes of Health.

The Effects of Electrical Stimulation Pulse Duration on Lingual Palatal Pressure Measures During Swallowing in Healthy Older Adults.

Limited research in swallowing physiology has suggested that the most common existing transcutaneous electrical stimulation (TES) protocol (VitalStim) may not penetrate to layers of tissue to affect deep swallowing muscles. TES amplitude is the primary parameter that determines the depth of electrical current penetration (DECP). Preliminary work suggests that replacing a long-pulse duration with a short-pulse duration can increase maximum amplitude tolerance (MAT) within subjects' comfort level. Increasing MAT may indicate a higher DECP. The current study evaluates this premise in reference to the effects of varying pulse duration on lingual-palatal pressure during swallowing. Thirty healthy older adults (60-70 years of age) participated in this study. Each subject swallowed three trials of 10 mL pudding under three TES conditions: no stimulation, short-pulse duration, and long-pulse duration. TES was delivered using two pairs of surface electrodes on the submental muscles. MAT and perceived discomfort levels were identified separately for short and long-pulse TES conditions. Lingual-palatal peak pressure, pressure integral, and pressure duration were measured under each condition. Two-way repeated measures ANOVAs were conducted to identify within subject effects of TES condition and tongue bulb location. Lingual-palatal pressure and pressure integral were significantly reduced in the short-pulse duration condition. MAT was significantly higher in the short-pulse duration versus the long-pulse duration condition. Furthermore, MAT was significantly correlated with lingual-palatal pressure. Changing pulse duration had no significant impact on tongue pressure duration. Results suggest that a short-pulse duration may penetrate deeper into muscles involved in swallowing. The specific impact is reflected in a reduced upward pressure of the tongue on the palate during swallowing. This 'restrictive' effect of TES on tongue pressure may have the potential to be used during a resistive exercise paradigm for tongue elevation during swallowing.

A comparison of accelerometry analysis methods for physical activity in older adult women and associations with health outcomes over time.

This study compared five different methods for analyzing accelerometer-measured physical activity (PA) in older adults and assessed the relationship between changes in PA and changes in physical function and depressive symptoms for each method. Older adult females (N = 144, Mage = 83.3 ± 6.4yrs) wore hip accelerometers for six days and completed measures of physical function and depressive symptoms at baseline and six months. Accelerometry data were processed by five methods to estimate PA: 1041 vertical axis cut-point, 15-second vector magnitude (VM) cut-point, 1-second VM algorithm (Activity Index (AI)), machine learned walking algorithm, and individualized cut-point derived from a 400-meter walk. Generalized estimating equations compared PA minutes across methods and showed significant differences between some methods but not others; methods estimated 6-month changes in PA ranging from 4 minutes to over 20 minutes. Linear mixed models for each method tested associations between changes in PA and health. All methods, except the individualized cut-point, had a significant relationship between change in PA and improved physical function and depressive symptoms. This study is among the first to compare accelerometry processing methods and their relationship to health. It is important to recognize the differences in PA estimates and relationship to health outcomes based on data processing method. Abbreviation: Machine Learning (ML); Short Physical Performance Battery (SPPB); Center of Epidemiologic Studies Depression Scale (CES-D); Physical Activity (PA); Activity Index (AI); Activities of Daily Living (ADL).

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

BACKGROUND: Whether 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. METHODS: We 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. RESULTS: After 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). CONCLUSIONS: A 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 REGISTRATION: Clinicaltrials.gov, NCT01072500.

Mitochondrial DNA m.13514G>A heteroplasmy is associated with depressive symptoms in the elderly.

OBJECTIVES: Mitochondrial DNA (mtDNA) heteroplasmy is a mixture of normal and mutated mtDNA molecules in a cell. High levels of heteroplasmy at several mtDNA sites in complex I lead to inherited neurological neurologic diseases and brain magnetic resonance imaging (MRI) abnormalities. Here, we test the hypothesis that mtDNA heteroplasmy at these complex I sites is associated with depressive symptoms in the elderly. METHODS: We examined platelet mtDNA heteroplasmy for associations with depressive symptoms among 137 participants over age 70 from the community-based Health, Aging and Body Composition Study. Depressive symptoms were assessed using the 10-point version of the Center for Epidemiologic Studies Depression Scale (CES-D 10). Complete mtDNA sequencing was performed and heteroplasmy derived for 5 mtDNA sites associated with neurologic mitochondrial diseases and tested for associations with depressive symptoms. RESULTS: Of 5 candidate complex I mtDNA mutations examined for effects on depressive symptoms, increased heteroplasmy at m.13514A>G, ND5, was significantly associated with higher CES-D score (P = .01). A statistically significant interaction between m.13514A > G heteroplasmy and sex was detected (P = .04); in sex-stratified analyses, the impact of m.13514A>G heteroplasmy was stronger in male (P = .003) than in female (P = .98) participants. Men in highest tertile of mtDNA heteroplasmy exhibited significantly higher (P = .0001) mean ± SE CES-D 10 scores, 5.37 ± 0.58, when compared with those in the middle, 2.13 ± 0.52, and lowest tertiles, 2.47 ± 0.58. No associations between the 4 other candidate sites and depressive symptoms were observed. CONCLUSIONS: Increased mtDNA heteroplasmy at m.13514A>G is associated with depressive symptoms in older men. Heteroplasmy may represent a novel biological risk factor for depression.

Wrist accelerometer shape feature derivation methods for assessing activities of daily living.

BACKGROUND: There has been an increasing interest in understanding the usefulness of wrist-based accelerometer data for physical activity (PA) assessment due to the ease of use and higher user compliance than other body placements. PA assessment studies have relied on machine learning methods which take accelerometer data in forms of variables, or feature vectors. METHODS: In this work, we introduce automated shape feature derivation methods to transform epochs of accelerometer data into feature vectors. As the first step, recurring patterns in the collected data are identified and placed in a codebook. Similarities between epochs of accelerometer data and codebook's patterns are the basis of feature calculations. In this paper, we demonstrate supervised and unsupervised approaches to learn codebooks. We evaluated these methods and compared them with the standard statistical measures for PA assessment. The experiments were performed on 146 participants who wore an ActiGraph GT3X+ accelerometer on the right wrist and performed 33 activities of daily living. RESULTS: Our evaluations show that the shape feature derivation methods were able to perform comparably with the standard wrist model (F1-score: 0.89) for identifying sedentary PAs (F1-scores of 0.86 and 0.85 for supervised and unsupervised methods, respectively). This was also observed for identifying locomotion activities (F1-scores: 0.87, 0.83, and 0.81 for the standard wrist, supervised, unsupervised models, respectively). All the wrist models were able to estimate energy expenditure required for PAs with low error (rMSE: 0.90, 0.93, and 0.90 for the standard wrist, supervised, and unsupervised models, respectively). CONCLUSION: The automated shape feature derivation methods offer insights into the performed activities by providing a summary of repeating patterns in the accelerometer data. Furthermore, they could be used as efficient alternatives (or additions) for manually engineered features, especially important for cases where the latter fail to provide sufficient information to machine learning methods for PA assessment.

Association between age-related reductions in testosterone and risk of prostate cancer-An analysis of patients' data with prostatic diseases.

The relationship between serum total testosterone and prostate cancer (PCa) risk is controversial. The hypothesis that faster age-related reduction in testosterone is linked with increased PCa risk remains untested. We conducted our study at a tertiary-level hospital in southeast of the USA, and derived data from the Medical Registry Database of individuals that were diagnosed of any prostate-related disease from 2001 to 2015. Cases were those diagnosed of PCa and had one or more measurements of testosterone prior to PCa diagnosis. Controls were those without PCa and had one or more testosterone measurements. Multivariable logistic regression models for PCa risk of absolute levels (one-time measure and 5-year average) and annual change in testosterone were respectively constructed. Among a total of 1,559 patients, 217 were PCa cases, and neither one-time measure nor 5-year average of testosterone was found to be significantly associated with PCa risk. Among the 379 patients with two or more testosterone measurements, 27 were PCa cases. For every 10 ng/dL increment in annual reduction of testosterone, the risk of PCa would increase by 14% [adjusted odds ratio, 1.14; 95% confidence interval (CI), 1.03-1.25]. Compared to patients with a relatively stable testosterone, patients with an annual testosterone reduction of more than 30 ng/dL had 5.03 [95% CI: 1.53, 16.55] fold increase in PCa risk. This implies a faster age-related reduction in, but not absolute level of serum total testosterone as a risk factor for PCa. Further longitudinal studies are needed to confirm this finding.

Associations of Accelerometer-Measured and Self-Reported Sedentary Time With Leukocyte Telomere Length in Older Women.

Few studies have assessed the association of sedentary time with leukocyte telomere length (LTL). In a cross-sectional study conducted in 2012-2013, we examined associations of accelerometer-measured and self-reported sedentary time with LTL in a sample of 1,481 older white and African-American women from the Women's Health Initiative and determined whether associations varied by level of moderate- to vigorous-intensity physical activity (MVPA). The association between sedentary time and LTL was evaluated using multiple linear regression models. Women were aged 79.2 (standard deviation, 6.7) years, on average. Self-reported sedentary time was not associated with LTL. In a model adjusting for demographic characteristics, lifestyle behaviors, and health-related factors, among women at or below the median level of accelerometer-measured MVPA, those in the highest quartile of accelerometer-measured sedentary time had significantly shorter LTL than those in the lowest quartile, with an average difference of 170 base pairs (95% confidence interval: 4, 340). Accelerometer-measured sedentary time was not associated with LTL in women above the median level of MVPA. Findings suggest that, on the basis of accelerometer measurements, higher sedentary time may be associated with shorter LTL among less physically active women.

The effect of intervening hospitalizations on the benefit of structured physical activity in promoting independent mobility among community-living older persons: secondary analysis of a randomized controlled trial.

BACKGROUND: Among older persons, disability is often precipitated by intervening illnesses and injuries leading to hospitalization. In the Lifestyle Interventions and Independence for Elders (LIFE) Study, a structured moderate-intensity physical activity program, compared with a health education program, was shown to significantly reduce the amount of time spent with major mobility disability (MMD) over the course of 3.5 years. We aimed to determine whether the benefit of the physical activity program in promoting independent mobility was diminished in the setting of intervening hospitalizations. METHODS: We analyzed data from a single-blinded, parallel group randomized trial (ClinicalTrials.gov: NCT01072500). In this trial, 1635 sedentary persons, aged 70-89 years, who had functional limitations but were able to walk 400 m, were randomized from eight US centers between February 2010 and December 2013: 818 to physical activity (800 received intervention) and 817 to health education (805 received intervention). Intervening hospitalizations and MMD, defined as the inability to walk 400 m, were assessed every 6 months for up to 3.5 years. RESULTS: For both the physical activity and health education groups, intervening hospitalizations were strongly associated with the initial onset of MMD and inversely associated with recovery from MMD, defined as a transition from initial MMD onset to no MMD. The benefit of the physical activity intervention did not differ significantly based on hospital exposure. For onset of MMD, the hazard ratios (HR) were 0.79 (95% confidence interval [CI] 0.58-1.1) and 0.77 (0.62-0.95) in the presence and absence of intervening hospitalizations, respectively (P-interaction, 0.903). For recovery of MMD, the magnitude of effect was modestly greater among participants who were hospitalized (HR 1.5, 95% CI 0.71-3.0) than in those who were not hospitalized (HR 1.2, 95% CI 0.88-1.7), but this difference did not achieve statistical significance (P-interaction, 0.670). CONCLUSIONS: Intervening hospitalizations had strong deleterious effects on the onset of MMD and recovery from MMD, but did not diminish the beneficial effect of the LIFE physical activity intervention in promoting independent mobility. To achieve sustained benefits over time, structured physical activity programs should be designed to accommodate acute illnesses and injuries leading to hospitalizations given their high frequency in older persons with functional limitations. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01072500 .