Structured Moderate Exercise and Biomarkers of Kidney Health in Sedentary Older Adults: The Lifestyle Interventions and Independence for Elders Randomized Clinical Trial.

Rationale & Objective: In the Lifestyle Interventions and Independence for Elders (LIFE) trial, a structured exercise intervention slowed kidney function decline in sedentary older adults. Biomarkers of kidney health could distinguish potential mechanisms for this beneficial effect. Study Design: Randomized controlled trial. Setting & Population: A total of 1,381 sedentary adults aged 70-89 years enrolled in the LIFE trial. Intervention: Structured, 2-year, moderate-intensity exercise intervention versus health education. Outcomes: Physical activity was measured by step count. Primary outcomes were changes in 14 serum and urine biomarkers of kidney health collected at baseline, year 1, and year 2. We determined the effect of randomization on changes in kidney measures and then evaluated observational associations of achieved activity on each measure. Results: Participants assigned to exercise walked on average 291 more steps per day than participants assigned to health education. The intervention was not significantly associated with changes in biomarkers of kidney health. In observational analyses, persons in the highest versus lowest quartile of activity (≥3,470 vs <1,568 steps/day) had significant improvement in urine albumin (mean, -0.22 mg albumin/g urine creatinine [interquartile range (IQR), -0.37 to -0.06]), alpha-1-microglobulin (-0.18 mg/L [-0.28 to -0.08]), trefoil factor-3 (-0.24 pg/mL [-0.35 to -0.13]), epidermal growth factor (0.19 pg/mL [0.06-0.32]), uromodulin (0.06 pg/mL [0.00-0.12]), interleukin 18 (-0.09 pg/mL [-0.15 to -0.03]), neutrophil gelatinase-associated lipocalin (-0.16 pg/mL [-0.24 to -0.07]), monocyte chemoattractant protein-1 (-0.25 pg/mL [-0.36 to -0.14]), clusterin (-0.16 pg/mL [-0.30 to -0.02]), serum tumor necrosis factor receptor-1 (-0.25 mg/dL [-0.39 to -0.11]) and tumor necrosis factor receptor-2 (-0.30 mg/dL [-0.44 to -0.16]). In sensitivity analyses, incremental changes in activity were most impactful on urine interleukin 18 and serum tumor necrosis factor-1. Limitations: The original study was not designed to assess the impact on kidney health. Non-white individuals and patients with advanced chronic kidney disease are underrepresented. Conclusions: Randomization to structured exercise did not improve kidney health at a group level. However, higher exercise was associated with concurrent improvements in biomarkers of glomerular injury, tubular function/repair, tubular injury, generalized inflammation, and tubulointerstitial repair/fibrosis. Plain-Language Summary: In the Lifestyle Interventions For Elders (LIFE) study, randomization to an exercise and physical activity intervention improved the slope of estimated glomerular filtration rate over 2 years compared with health education among older adults. In this study, we sought to determine whether there were specific biomarkers of kidney health that were affected by the exercise and physical activity intervention to investigate potential mechanisms for this positive impact on kidney decline. We found that randomization to the intervention did not improve any of the 14 measures of kidney tubule health. However, in observational analyses, higher activity was independently associated with improvements in several domains, especially tubular injury and generalized inflammation. These results help to clarify the impact of physical activity on kidney health.

Methods for estimating insulin resistance from untargeted metabolomics data.

CONTEXT: Insulin resistance is associated with multiple complex diseases; however, precise measures of insulin resistance are invasive, expensive, and time-consuming. OBJECTIVE: Develop estimation models for measures of insulin resistance, including insulin sensitivity index (SI) and homeostatic model assessment of insulin resistance (HOMA-IR) from metabolomics data. DESIGN: Insulin Resistance Atherosclerosis Family Study (IRASFS). SETTING: Community based. PARTICIPANTS: Mexican Americans (MA) and African Americans (AA). MAIN OUTCOME: Estimation models for measures of insulin resistance, i.e. SI and HOMA-IR. RESULTS: Least Absolute Shrinkage and Selection Operator (LASSO) and Elastic Net regression were used to build insulin resistance estimation models from 1274 metabolites combined with clinical data, e.g. age, sex, body mass index (BMI). Metabolite data were transformed using three approaches, i.e. inverse normal transformation, standardization, and Box Cox transformation. The analysis was performed in one MA recruitment site (San Luis Valley, Colorado (SLV); N = 450) and tested in another MA recruitment site (San Antonio, Texas (SA); N = 473). In addition, the two MA recruitment sites were combined and estimation models tested in the AA recruitment sample (Los Angeles, California; N = 495). Estimated and empiric SI were correlated in the SA (r2 = 0.77) and AA (r2 = 0.74) testing datasets. Further, estimated and empiric SI were consistently associated with BMI, low-density lipoprotein cholesterol (LDL), and triglycerides. We applied similar approaches to estimate HOMA-IR with similar results. CONCLUSIONS: We have developed a method for estimating insulin resistance with metabolomics data that has the potential for application to a wide range of biomedical studies and conditions.

Audio or Video? Access to Pediatric Neurology Outpatient Services Varies by the Type of Telehealth, Especially for Black Children.

BACKGROUND: Children of minority race/ethnicity face barriers to accessing specialty services. During the COVID pandemic, health insurance companies reimbursed telehealth services. Our objective was to evaluate the effect of audio versus video visits on children's access to outpatient neurology services, particularly for Black children. METHODS: Using Electronic Health Record data, we collected information about children who had outpatient neurology appointments in a tertiary care children's hospital in North Carolina from March 10, 2020, to March 9, 2021. We used multivariable models to compare appointment outcomes (canceled vs completed, and missed vs completed) by visit type. We then conducted similar evaluation for the subgroup of Black children. RESULTS: A total of 1250 children accounted for 3829 scheduled appointments. Audio users were more likely to be Black and Hispanic, and to have public health insurance than video users. Adjusted odds ratio (aOR) for appointments completed versus canceled was 10 for audio and 6 for video, compared to in-person appointments. Audio visits were twice as likely as in-person visits to be completed versus missed; video visits were not different. For the subgroup of Black children, aOR for appointments completed versus canceled for audio was 9 and video was 5, compared to in-person appointments. For Black children, audio visits were 3 times as likely as in-person visits to be completed versus missed; video visits were not different. CONCLUSIONS: Audio visits improved access to pediatric neurology services, especially for Black children. Reversal of policies to reimburse audio visits could deepen the socioeconomic divide for children's access to neurology services.

A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.

Evaluation of the Linear Composite Conjecture for Unidimensional IRT Scale for Multidimensional Responses.

The linear composite direction represents, theoretically, where the unidimensional scale would lie within a multidimensional latent space. Using compensatory multidimensional IRT, the linear composite can be derived from the structure of the items and the latent distribution. The purpose of this study was to evaluate the validity of the linear composite conjecture and examine how well a fitted unidimensional IRT model approximates the linear composite direction in a multidimensional latent space. Simulation experiment results overall show that the fitted unidimensional IRT model sufficiently approximates linear composite direction when correlation between bivariate latent variables is positive. When the correlation between bivariate latent variables is negative, instability occurs when the fitted unidimensional IRT model is used to approximate linear composite direction. A real data experiment was also conducted using 20 items from a multiple-choice mathematics test from American College Testing.

Gradient and Acceleration of Decline in Physical and Cognitive Functions in Older Adults: A Disparity Analysis.

BACKGROUND: Substantive previous work has shown that both gait speed and global cognition decline as people age. Rates of their decline, as opposed to cross-sectional measurements, could be more informative of future functional status and other clinical outcomes because they more accurately represent deteriorating systems. Additionally, understanding the sex and racial disparity in the speed of deterioration, if any, is also important as ethnic minorities are at an increased risk of mobility disability and dementia. METHOD: Data from 2 large longitudinal intervention studies were integrated. Rates of decline were derived from individual-level measures of gait speed of 400-m walk and scores on the Modified Mini Mental State Examination (3MSE). We also assessed age-associated declines and accelerations in changes across the ages represented in the studies (age range 53-90). RESULTS: The mean rate of decline in 400-m gait speed across individuals was 0.03 m/s per year, and multivariable analysis showed a significant acceleration in decline of -0.0013 m/s/y2 (p < .001). Both race and sex moderated the rate of decline. For global cognition, the mean rate of decline was 0.05 of a point per year on the 3MSE scale, and acceleration in the rate of decline was significant (-0.017 point/y2, p < .001), but neither sex nor race moderated the decline. CONCLUSION: Rate of decline in physical but not cognitive function appears moderated by sex and race. This finding, as well as rates and accelerations of decline estimated herein, could inform future intervention studies. CLINICAL TRIALS REGISTRATION NUMBER: NCT00017953 (Look AHEAD); NCT01410097 (Look AHEAD ancillary); NCT00116194 (LIFE).

Effect of Structured, Moderate Exercise on Kidney Function Decline in Sedentary Older Adults: An Ancillary Analysis of the LIFE Study Randomized Clinical Trial.

Importance: Observational evidence suggests that higher physical activity is associated with slower kidney function decline; however, to our knowledge, no large trial has evaluated whether activity and exercise can ameliorate kidney function decline in older adults. Objective: To evaluate whether a moderate-intensity exercise intervention can affect the rate of estimated glomerular filtration rate per cystatin C (eGFRCysC) change in older adults. Design, Setting, and Participants: This ancillary analysis of the Lifestyle Interventions and Independence For Elders randomized clinical trial enrolled 1199 community-dwelling, sedentary adults aged 70 to 89 years with mobility limitations and available blood specimens. The original trial was conducted across 8 academic centers in the US from February 2010 through December 2013. Data for this study were analyzed from March 29, 2021, to February 28, 2022. Interventions: Structured, 2-year, partially supervised, moderate-intensity physical activity and exercise (strength, flexibility) intervention compared with a health education control intervention with 2-year follow-up. Physical activity was measured by step count and minutes of moderate-intensity activity using accelerometers. Main Outcomes and Measures: The primary outcome was change in eGFRCysC. Rapid eGFRCysC decline was defined by the high tertile threshold of 6.7%/y. Results: Among the 1199 participants in the analysis, the mean (SD) age was 78.9 (5.2) years, and 800 (66.7%) were women. At baseline, the 2 groups were well balanced by age, comorbidity, and baseline eGFRCysC. The physical activity and exercise intervention resulted in statistically significantly lower decline in eGFRCysC over 2 years compared with the health education arm (mean difference, 0.96 mL/min/1.73 m2; 95% CI, 0.02-1.91 mL/min/1.73 m2) and lower odds of rapid eGFRCysC decline (odds ratio, 0.79; 95% CI, 0.65-0.97). Conclusions and Relevance: Results of this ancillary analysis of a randomized clinical trial showed that when compared with health education, a physical activity and exercise intervention slowed the rate of decline in eGFRCysC among community-dwelling sedentary older adults. Clinicians should consider targeted recommendation of physical activity and moderate-intensity exercise for older adults as a treatment to slow decline in eGFRCysC. Trial Registration: ClinicalTrials.gov Identifier: NCT01072500.

Is Wrist Accelerometry Suitable for Threshold Scoring? A Comparison of Hip-Worn and Wrist-Worn ActiGraph Data in Low-Active Older Adults With Obesity.

BACKGROUND: Hip- and wrist-worn ActiGraph accelerometers are widely used in research on physical activity as they offer an objective assessment of movement intensity across the day. Herein we characterize and contrast key structured physical activities and common activities of daily living via accelerometry data collected at the hip and wrist from a sample of community-dwelling older adults. METHODS: Low-active, older adults with obesity (age 60+ years) were fit with an ActiGraph GT3X+ accelerometer on their nondominant wrist and hip before completing a series of tasks in a randomized order, including sitting/standing, sweeping, folding laundry, stair climbing, ambulation at different intensities, and cycling at different intensities. Participants returned a week later and completed the tasks once again. Vector magnitude counts/second were time-matched during each task and then summarized into counts/minute (CPM). RESULTS: Monitors at both wear locations similarly characterized standing, sitting, and ambulatory tasks. A key finding was that light home chores (sweeping, folding laundry) produced higher and more variable CPM values than fast walking via wrist ActiGraph. Regression analyses revealed wrist CPM values were poor predictors of hip CPM values, with devices aligning best during fast walking (R2 = 0.25) and stair climbing (R2 = 0.35). CONCLUSIONS: As older adults spend a considerable portion of their day in nonexercise activities of daily living, researchers should be cautious in the use of simply acceleration thresholds for scoring wrist-worn accelerometer data. Methods for better classifying wrist-worn activity monitor data in older adults are needed.

Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes.

BACKGROUND: Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis. METHODS: We performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. RESULTS: We replicated 2 loci (rs9369640 and rs9349379 near PHACTR1 and rs10757278 near CDKN2B) for CAC and one locus for cIMT (rs7412 and rs445925 near APOE-APOC1) that were previously reported in the general EA populations. We identified one novel CAC locus (rs8000449 near CSNK1A1L/LINC00547/POSTN at 13q13.3) at P=2.0×10-8 in EA. No additional loci were identified with the meta-analyses of EA and African ancestry. The expression quantitative trait loci analysis with nearby expressed genes derived from arterial wall and metabolic tissues from the Genotype-Tissue Expression project pinpoints POSTN, encoding a matricellular protein involved in bone formation and bone matrix organization, as the potential candidate gene at this locus. In addition, we found significant associations (P<3.1×10-4) for 3 previously reported coronary artery disease loci for these subclinical atherosclerotic phenotypes (rs2891168 near CDKN2B-AS1 and rs11170820 near FLJ12825 for CAC, and rs7412 near APOE for cIMT). CONCLUSIONS: Our results provide potential biological mechanisms that could link CAC and cIMT to increased cardiovascular disease risk in individuals with T2D.

Conversion between the Modified Mini-Mental State Examination (3MSE) and the Mini-Mental State Examination (MMSE).

BACKGROUND: The Modified Mini-Mental State Examination (3MSE) and the Mini-Mental State Examination (MMSE) are two commonly used instruments for assessing cognitive function. Although conversion between 3MSE and MMSE is useful in applications such as integrative data analysis, there are limited published reports on the topic. Our objective is to provide a dual tool: (1) an item-level conversion tool to score responses for deriving both 3MSE and MMSE measures, and (2) cross-walk tables to facilitate quick conversion between 3MSE and MMSE. METHODS: An SAS program tool allows scoring of 3MSE item-level responses into MMSE score. Using integrated data sets (n = 8346), actual 3MSE and MMSE scores obtained from the same individuals were linked to form cross-walk tables. RESULTS: An SAS conversion program was made available. Cross-walk tables were derived. Validation sample shows bias is -0.11 (standard deviation = 1.02) in 3MSE→MMSE; the converse had substantially large bias. DISCUSSION: The 3MSE→MMSE conversion table can be used in clinical practice and legacy system data.

Association of Objectively Measured Timing of Physical Activity Bouts With Cardiovascular Health in Type 2 Diabetes.

OBJECTIVE: Moderate- to vigorous-intensity physical activity (MVPA) improves cardiovascular health. Few studies have examined MVPA timing. We examined the associations of timing of bout-related MVPA with cardiorespiratory fitness and cardiovascular risk in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: Baseline 7-day hip-worn accelerometry data from Look AHEAD participants (n = 2,153, 57% women) were analyzed to identify bout-related MVPA (≥3 METs/min for ≥10 min). Cardiorespiratory fitness was assessed by maximal graded exercise test. Participants were categorized into six groups on the basis of the time of day with the majority of bout-related MVPA (METs × min): ≥50% of bout-related MVPA during the same time window (morning, midday, afternoon, or evening), <50% of bout-related MVPA in any time category (mixed; the reference group), and ≤1 day with bout-related MVPA per week (inactive). RESULTS: Cardiorespiratory fitness was highly associated with timing of bout-related MVPA (P = 0.0005), independent of weekly bout-related MVPA volume and intensity. Importantly, this association varied by sex (P = 0.02). In men, the midday group had the lowest fitness (ß = -0.46 [95% CI -0.87, -0.06]), while the mixed group in women was the least fit. Framingham risk score (FRS) was associated with timing of bout-related MVPA (P = 0.02), which also differed by sex (P = 0.0007). The male morning group had the highest 4-year FRS (2.18% [0.70, 3.65]), but no association was observed in women. CONCLUSIONS: Timing of bout-related MVPA is associated with cardiorespiratory fitness and cardiovascular risk in men with type 2 diabetes, independent of bout-related MVPA volume and intensity. Prospective studies are needed to determine the impacts of MVPA timing on cardiovascular health.

Heterogeneity in Association Between Cognitive Function and Gait Speed Among Older Adults: An Integrative Data Analysis Study.

BACKGROUND: Increasing evidence shows that cognition and gait speed are associated and are important measures of health among older adults. However, previous studies have used different methods to assess these 2 outcomes and lack sufficient sample size to examine heterogeneity among subgroups. This study examined how the relationship between global cognitive function and gait speed are influenced by age, gender, and race utilizing an integrated data analysis approach. METHOD: Data on cognition (Montreal Cognitive Assessment [MoCA], Mini-Mental Status Examination [MMSE], and Modified Mini-Mental State Examination [3MSE]) and gait speed (range: 4-400 m) were acquired and harmonized from 25 research studies (n = 2802) of adults aged 50+ from the Wake Forest Older American Independence Center. Multilevel regression models examined the relationship between predicted values of global cognitive function (MoCA) and gait speed (4-m walk), including heterogeneity by age, race, and gender. RESULTS: Global cognitive function and gait speed exhibited a consistent positive relationship among whites with increasing age, while this was less consistent for African Americans. That is, there was a low correlation between global cognitive function and gait speed among African Americans aged 50-59, a positive correlation in their 60s and 70s, then a negative correlation thereafter. CONCLUSION: Global cognition and gait speed exhibited a curvilinear U-shaped relationship among whites; however, the association becomes inverse in African Americans. More research is needed to understand this racial divergence and could aid in identifying interventions to maintain cognitive and gait abilities across subgroups.

Robustness of Projective IRT to Misspecification of the Underlying Multidimensional Model.

As a method to derive a "purified" measure along a dimension of interest from response data that are potentially multidimensional in nature, the projective item response theory (PIRT) approach requires first fitting a multidimensional item response theory (MIRT) model to the data before projecting onto a dimension of interest. This study aims to explore how accurate the PIRT results are when the estimated MIRT model is misspecified. Specifically, we focus on using a (potentially misspecified) two-dimensional (2D)-MIRT for projection because of its advantages, including interpretability, identifiability, and computational stability, over higher dimensional models. Two large simulation studies (I and II) were conducted. Both studies examined whether the fitting of a 2D-MIRT is sufficient to recover the PIRT parameters when multiple nuisance dimensions exist in the test items, which were generated, respectively, under compensatory MIRT and bifactor models. Various factors were manipulated, including sample size, test length, latent factor correlation, and number of nuisance dimensions. The results from simulation studies I and II showed that the PIRT was overall robust to a misspecified 2D-MIRT. Smaller third and fourth simulation studies were done to evaluate recovery of the PIRT model parameters when the correctly specified higher dimensional MIRT or bifactor model was fitted with the response data. In addition, a real data set was used to illustrate the robustness of PIRT.

Longitudinal partially ordered data analysis for preclinical sarcopenia.

Sarcopenia is a geriatric syndrome characterized by significant loss of muscle mass. Based on a commonly used definition of the condition that involves three measurements, different subclinical and clinical states of sarcopenia are formed. These states constitute a partially ordered set (poset). This article focuses on the analysis of longitudinal poset in the context of sarcopenia. We propose an extension of the generalized linear mixed model and a recoding scheme for poset analysis such that two submodels-one for ordered categories and one for nominal categories-that include common random effects can be jointly estimated. The new poset model postulates random effects conceptualized as latent variables that represent an underlying construct of interest, that is, susceptibility to sarcopenia over time. We demonstrate how information can be gleaned from nominal sarcopenic states for strengthening statistical inference on a person's susceptibility to sarcopenia.

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

OBJECTIVES: 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. DESIGN: 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. SETTING: Lifestyle Interventions and Independence for Elders Study PARTICIPANTS: Older adult participants (78.4 years; N = 507) at risk for MMD. INTERVENTION: 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. MEASUREMENTS: 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. RESULTS: 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. CONCLUSION: 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.

A Case for Promoting Movement Medicine: Preventing Disability in the LIFE Randomized Controlled Trial.

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.

Gleaning Information for Cognitive Operations from Don't Know Responses in Cognitive and Noncognitive Assessments.

The Don't Know (DK) response - taking the form of an omitted response or not-reached at the end of a cognitive test, or explicitly presented as a response option in a social survey - contains important information that is often overlooked. Direct psychometric modeling efforts for DK responses are few and far between. In this article, the linear logistic test model (LLTM) is proposed for delineating the impacts of cognitive operations for a test that contains DK responses. We assume that the DK response is a valid response. The assumption is reasonable for many situations, including low-stakes cognitive tests and attitudinal assessments. By extracting information embedded in the DK response, the method shows how DK can inform the latent construct of interest and the cognitive operations underlying the response to stimuli. Using a proven recoding scheme, the LLTM could be implemented through commonly used programs such as PROC GLIMMIX. Two simulation experiments to evaluate how well the parameters can be recovered were conducted. In addition, two real data examples, from a noncognitive test of health belief assessment and a cognitive test of knowledge in diabetes, are also presented as case studies to illustrate the LLTM for DK response.

An Algorithm for Creating Virtual Controls Using Integrated and Harmonized Longitudinal Data.

We introduce a strategy for creating virtual control groups-cases generated through computer algorithms that, when aggregated, may serve as experimental comparators where live controls are difficult to recruit, such as when programs are widely disseminated and randomization is not feasible. We integrated and harmonized data from eight archived longitudinal adolescent-focused data sets spanning the decades from 1980 to 2010. Collectively, these studies examined numerous psychosocial variables and assessed past 30-day alcohol, cigarette, and marijuana use. Additional treatment and control group data from two archived randomized control trials were used to test the virtual control algorithm. Both randomized controlled trials (RCTs) assessed intentions, normative beliefs, and values as well as past 30-day alcohol, cigarette, and marijuana use. We developed an algorithm that used percentile scores from the integrated data set to create age- and gender-specific latent psychosocial scores. The algorithm matched treatment case observed psychosocial scores at pretest to create a virtual control case that figuratively "matured" based on age-related changes, holding the virtual case's percentile constant. Virtual controls matched treatment case occurrence, eliminating differential attrition as a threat to validity. Virtual case substance use was estimated from the virtual case's latent psychosocial score using logistic regression coefficients derived from analyzing the treatment group. Averaging across virtual cases created group estimates of prevalence. Two criteria were established to evaluate the adequacy of virtual control cases: (1) virtual control group pretest drug prevalence rates should match those of the treatment group and (2) virtual control group patterns of drug prevalence over time should match live controls. The algorithm successfully matched pretest prevalence for both RCTs. Increases in prevalence were observed, although there were discrepancies between live and virtual control outcomes. This study provides an initial framework for creating virtual controls using a step-by-step procedure that can now be revised and validated using other prevention trial data.

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND: Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS: Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS: Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500.