Effect of Long-term Exercise Training on Physical Performance and Cardiorespiratory Function in Adults With CKD: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: The safety and efficacy of long-term exercise training in reducing physical functional loss in older adults with advanced CKD and comorbidity is uncertain. STUDY DESIGN: Multicenter, parallel group, randomized controlled trial. SETTINGS & PARTICIPANTS: Adults 55 years and older with estimated glomerular filtration rate (eGFR) of 15 to <45 mL/min/1.73 m2 enrolled from centers in Baltimore and Boston. INTERVENTION: Twelve months of in-center supervised exercise training incorporating majority aerobic but also muscle strengthening activities or a group health education control intervention, randomly assigned in 1:1 ratio. OUTCOME: Primary outcomes were cardiorespiratory fitness and submaximal gait at 6 and 12 months quantified by peak oxygen consumption (Vo2peak) on graded exercise treadmill test and distance walked on the 6-minute walk test, respectively. Secondary outcomes were changes in lower extremity function, eGFR, albuminuria, glycemia, blood pressure, and body mass index. RESULTS: Among 99 participants, the mean age was 68 years, 62% were African American, and the mean eGFR was 33 mL/min/1.73 m2; 59% had diabetes, and 29% had coronary artery disease. Among those randomized to exercise, 59% of exercise sessions were attended in the initial 6 months. Exercise was well tolerated without excess occurrence of adverse events. At 6 months, aerobic capacity was higher among exercise participants (17.9 ± 5.5 vs 15.9 ± 7.0 mL/kg/min, P = 0.03), but the differences were not sustained at 12 months. The 6-minute walk distance improved more in the exercise group (adjusted difference: 98 feet [P = 0.02; P = 0.03 for treatment-by-time interaction]). The exercise group had greater improvements on the Timed Up and Go Test (P = 0.04) but not the Short Physical Performance Battery (P = 0.8). LIMITATIONS: Planned sample size was not reached. Loss to follow-up and dropout were greater than anticipated. CONCLUSIONS: Among adults aged ≥55 years with CKD stages 3b-4 and a high level of medical comorbidity, a 12-month program of in-center aerobic and resistance exercise training was safe and associated with improvements in physical functioning. FUNDING: Government grants (National Institutes of Health). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01462097.

Synergistic Associations of Depressive Symptoms and Executive Functions With Longitudinal Trajectories of Diabetes Biomarkers Among Urban-Dwelling Adults Without Diabetes.

OBJECTIVE: Depressive symptoms and executive functions (EFs) have recently emerged as novel risk factors for type 2 diabetes, but it is unknown if these factors interact to influence diabetes pathophysiology across the life span. We examined the synergistic associations of depressive symptoms and EFs with longitudinal trajectories of diabetes diagnostic criteria among middle-aged and older adults without diabetes. METHODS: Participants were 1257 African American and White, urban-dwelling adults from the Healthy Aging in Neighborhoods of Diversity across the Life Span study who were assessed up to three times over a 13-year period (2004-2017). At baseline, participants completed the Center for Epidemiological Studies-Depression scale and measures of EFs-Trail Making Test Part B, verbal fluency, and Digit Span Backward-for a composite EFs score, and provided blood samples at each follow-up for glycated hemoglobin and fasting serum glucose. RESULTS: A total of 155 and 220 individuals developed diabetes or prediabetes at wave 3 and wave 4, respectively. Linear mixed-effects regression models adjusting for sociodemographic factors, diabetes risk factors, and antidepressant medications revealed significant three-way interactions of Center for Epidemiological Studies-Depression, EFs, and age on change in glycated hemoglobin (b = -0.0001, p = .005) and in fasting serum glucose (b = -0.0004, p < .001), such that among individuals with lower but not higher EFs, elevated depressive symptoms were associated with steeper age-related increases in diabetes biomarkers over time. CONCLUSIONS: Depressive symptoms and lower EFs may interactively accelerate trajectories of key diagnostic criteria, thereby increasing the risk for earlier diabetes incidence. Identifying individuals in this high-risk group may be an important clinical priority for earlier intervention, which has the promise of preventing or delaying this debilitating disease.

Low Back Pain and Substance Use: Diagnostic and Administrative Coding for Opioid Use and Dependence Increased in U.S. Older Adults with Low Back Pain.

OBJECTIVE: Low back pain (LBP) is a leading cause of pain and disability. Substance use complicates the management of LBP, and potential risks increase with aging. Despite implications for an aging, diverse U.S. population, substance use and LBP comorbidity remain poorly defined. The objective of this study was to characterize LBP and substance use diagnoses in older U.S. adults by age, gender, and race. DESIGN: Cross-sectional study of a random national sample. SUBJECTS: Older adults including 1,477,594 U.S. Medicare Part B beneficiaries. METHODS: Bayesian analysis of 37,634,210 claims, with 10,775,869 administrative and 92,903,649 diagnostic code assignments. RESULTS: LBP was diagnosed in 14.8±0.06% of those more than 65 years of age, more in females than in males (15.8±0.08% vs. 13.4±0.09%), and slightly less in those more than 85 years of age (13.3±0.2%). Substance use diagnosis varied by substance: nicotine, 9.6±0.02%; opioid, 2.8±0.01%; and alcohol, 1.3±0.01%. Substance use diagnosis declined with advancing age cohort. Opioid use diagnosis was markedly higher for those in whom LBP was diagnosed (10.5%) than for those not diagnosed with LBP (1.5%). Most older adults (54.9%) with an opioid diagnosis were diagnosed with LBP. Gender differences were modest. Relative rates of substance use diagnoses in LBP were modest for nicotine and alcohol. CONCLUSIONS: Older adults with LBP have high relative rates of opioid diagnoses, irrespective of gender or age. Most older adults with opioid-related diagnoses have LBP, compared with a minority of those not opioid diagnosed. In caring for older adults with LBP or opioid-related diagnoses, health systems must anticipate complexity and support clinicians, patients, and caregivers in managing pain comorbidities. Older adults may benefit from proactive incorporation of non-opioid pain treatments. Further study is needed.

Evaluating Test-Retest Reliability of Fatigability in Chronic Stroke.

OBJECTIVES: The subjective nature of fatigue may contribute to inconsistencies in prevalence rates for post-stroke fatigue. More objective performance fatigue measures may offer a more reliable construct of fatigue. Our goal was to establish test-retest reliability of fatigability in stroke during 6-minute walk (6MW) testing. Relationships between post-stoke fatigability and other constructs were assessed. MATERIALS AND METHODS: Twenty-three hemiparetic stroke survivors underwent two 6MW tests with portable metabolic monitoring performed at least 48 hours apart. Fatigability was defined as ratio of change in walking speed to distance covered during the 6MW. 6MW oxygen consumption (VO2), peak aerobic capacity (VO2peak), walking speed over-ground, dynamic gait index, fatigue, falls efficacy, and BMI were measured. RESULTS: Fatigability was highly correlated between both 6MW trials (ICC = 0.99, p < 0.001) with no significant difference between trials (0.08, p = 0.48). The strongest correlation was between fatigability and 6MW VO2 trial 1 and 2 (r = 0.92, p < 0.001 and r = 0.95, p < 0.001, respectively). Moderate-to-strong relationships were observed between fatigability for 6MW and fastest-comfortable walking speed (r = -0.82 and -0.77), self-selected walking speed (r = -7.8 and -0.78), 6MW walking speed (r = -0.80 and 0.80, VO2peak (r = -0.47 and -0.48) (p < 0.001), and DGI (r = -0.70 and -0.68, p < 0.001). CONCLUSION: This study establishes test-retest reliability for an objective measure of fatigue in stroke-related disability. The strong correlations between fatigability and other functional measures also provides insight into the contributors underlying fatigability in this population. REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01322607.

Sarcopenia in Peripheral Arterial Disease: Prevalence and Effect on Functional Status.

OBJECTIVES: (1) To determine the prevalence of sarcopenia in older men with peripheral arterial disease (PAD); (2) to compare a subgroup of the group with age-, race-, sex-, and body mass index (BMI)-matched non-PAD control counterparts, and (3) to compare the functional status of those with PAD with and without sarcopenia. DESIGN: Cohort study. SETTING: Medical center. PARTICIPANTS: Sedentary community-dwelling men (N=108; age, >50y) with a confirmed diagnosis of PAD (44% blacks; BMI, 27.8±0.4kg/m2; ankle-brachial index, .62±.01). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry scans were used to assess appendicular lean mass and determine the prevalence of sarcopenia by/height2. Treadmill tests were used to determine claudication onset time, peak walking time, and claudication recovery time. 6-Minute walk distance was also measured. RESULTS: Sarcopenia prevalence in our PAD cohort was 25%. The PAD subgroup (n=42) matched with control counterparts in terms of race, sex, age, and BMI had higher prevalence rates than did their non-PAD counterparts (23.8% vs 2.4%; P<.05). Individuals with sarcopenia (n=28) had a shorter 6-minute walk distance (326±18.8m vs 380±9.7m; P<.05) and higher claudication recovery time (592±98s vs 395±29s; P<.05) than did individuals with PAD but without sarcopenia (n=80). There was no difference in claudication onset time or peak walking time between the PAD groups. CONCLUSIONS: Men with PAD demonstrate a high prevalence of sarcopenia. Those with sarcopenia and PAD demonstrate decreased mobility function.

Differential Associations of Socioeconomic Status With Global Brain Volumes and White Matter Lesions in African American and White Adults: the HANDLS SCAN Study.

OBJECTIVE: The aim of the study was to examine interactive relations of race and socioeconomic status (SES) to magnetic resonance imaging (MRI)-assessed global brain outcomes with previously demonstrated prognostic significance for stroke, dementia, and mortality. METHODS: Participants were 147 African Americans (AAs) and whites (ages 33-71 years; 43% AA; 56% female; 26% below poverty) in the Healthy Aging in Neighborhoods of Diversity across the Life Span SCAN substudy. Cranial MRI was conducted using a 3.0 T unit. White matter (WM) lesion volumes and total brain, gray matter, and WM volumes were computed. An SES composite was derived from education and poverty status. RESULTS: Significant interactions of race and SES were observed for WM lesion volume (b = 1.38; η = 0.036; p = .028), total brain (b = 86.72; η = 0.042; p < .001), gray matter (b = 40.16; η = 0.032; p = .003), and WM (b = 46.56; η = 0.050; p < .001). AA participants with low SES exhibited significantly greater WM lesion volumes than white participants with low SES. White participants with higher SES had greater brain volumes than all other groups (albeit within normal range). CONCLUSIONS: Low SES was associated with greater WM pathology-a marker for increased stroke risk-in AAs. Higher SES was associated with greater total brain volume-a putative global indicator of brain health and predictor of mortality-in whites. Findings may reflect environmental and interpersonal stressors encountered by AAs and those of lower SES and could relate to disproportionate rates of stroke, dementia, and mortality.

Strength Training for Skeletal Muscle Endurance after Stroke.

BACKGROUND AND PURPOSE: Initial studies support the use of strength training (ST) as a safe and effective intervention after stroke. Our previous work shows that relatively aggressive, higher intensity ST translates into large effect sizes for paretic and non-paretic leg muscle volume, myostatin expression, and maximum strength post-stroke. An unanswered question pertains to how our unique ST model for stroke impacts skeletal muscle endurance (SME). Thus, we now report on ST-induced adaptation in the ability to sustain isotonic muscle contraction. METHODS: Following screening and baseline testing, hemiparetic stroke participants were randomized to either ST or an attention-matched stretch control group (SC). Those in the ST group trained each leg individually to muscle failure (20 repetition sets, 3× per week for 3 months) on each of three pneumatic resistance machines (leg press, leg extension, and leg curl). Our primary outcome measure was SME, quantified as the number of submaximal weight leg press repetitions possible at a specified cadence. The secondary measures included one-repetition maximum strength, 6-minute walk distance (6MWD), 10-meter walk speeds, and peak aerobic capacity (VO2 peak). RESULTS: ST participants (N = 14) had significantly greater SME gains compared with SC participants (N = 16) in both the paretic (178% versus 12%, P < .01) and non-paretic legs (161% versus 12%, P < .01). These gains were accompanied by group differences for 6MWD (P < .05) and VO2 peak (P < .05). CONCLUSION: Our ST regimen had a large impact on the capacity to sustain submaximal muscle contraction, a metric that may carry more practical significance for stroke than the often reported measures of maximum strength.

Association between physical performance and all-cause mortality in CKD.

In older adults, measurements of physical performance assess physical function and associate with mortality and disability. Muscle wasting and diminished physical performance often accompany CKD, resembling physiologic aging, but whether physical performance associates with clinical outcome in CKD is unknown. We evaluated 385 ambulatory, stroke-free participants with stage 2-4 CKD enrolled in clinic-based cohorts at the University of Washington and University of Maryland and Veterans Affairs Maryland Healthcare systems. We compared handgrip strength, usual gait speed, timed up and go (TUAG), and 6-minute walking distance with normative values and constructed Cox proportional hazards models and receiver operating characteristic curves to test associations with all-cause mortality. Mean age was 61 years and the mean estimated GFR was 41 ml/min per 1.73 m(2). Measures of lower extremity performance were at least 30% lower than predicted, but handgrip strength was relatively preserved. Fifty deaths occurred during the median 3-year follow-up period. After adjustment, each 0.1-m/s decrement in gait speed associated with a 26% higher risk for death, and each 1-second longer TUAG associated with an 8% higher risk for death. On the basis of the receiver operating characteristic analysis, gait speed and TUAG more strongly predicted 3-year mortality than kidney function or commonly measured serum biomarkers. Adding gait speed to a model that included estimated GFR significantly improved the prediction of 3-year mortality. In summary, impaired physical performance of the lower extremities is common in CKD and strongly associates with all-cause mortality.

Distinct functions of social support and cognitive function among older adults.

UNLABELLED: BACKGROUND/STUDY CONTEXT: Social support has been shown to buffer cognitive decline in older adults; however, few studies have examined the association of distinct functions of perceived social support and cognitive function. The current study examined the relations between distinct functions of social support and numerous cognitive domains in older adults. METHODS: Data were derived from a cross-sectional, correlational study of cardiovascular risk factors, cognitive function, and neuroimaging. The participants were 175 older adults with a mean age of 66.32. A number of neuropsychological tests and the Interpersonal Support Evaluation List were administered. Multiple linear regression analyses were conducted to determine cross-sectional relations of social support to cognitive function after controlling for age, gender, education, depressive symptomatology, systolic blood pressure, body mass index, total cholesterol, and fasting glucose. RESULTS: No significant positive relations were found between distinct functions of social support and cognitive function in any domain; however, inverse relations emerged such that greater social support across several functions was associated with poorer nonverbal memory and response inhibition. CONCLUSION: Results suggest that the receipt of social support may be a burden for some older adults. Within the current study, fluid cognitive abilities reflected this phenomenon. The mechanism through which social support is associated with poorer cognitive function in some domains deserves further exploration.

The short physical performance battery as a predictor of functional capacity after stroke.

BACKGROUND: The short physical performance battery is a widely used instrument for quantifying lower extremity function in older adults. However, its utility for predicting endurance-based measures of functional performance that are more difficult to conduct in clinical settings is unknown. An understanding of this could be particularly relevant in mobility impaired stroke survivors, for whom establishing the predictive strength of simpler to perform measures would aid in tracking broader categories of functional disability. This cross-sectional study was conducted to determine whether the short physical performance battery is related to functional measures with a strong endurance component. METHODS: Functional measures (short physical performance battery, peak aerobic capacity, and 6-minute walk) were obtained and compared for the first time in stroke survivors with hemiparetic gait. Pearson correlation coefficients were used to assess strength of the relationships (α P < .05). RESULTS: Forty-three stroke participants performed a standardized short physical performance battery. Forty-one of the subjects completed a 6-minute walk, and 40 completed a peak treadmill test. Mean short physical performance battery (6.3 ± 2.5 [mean ± SD]), 6-minute walk (242 ± 115 meters), and peak aerobic capacity (17.4 ± 5.4 mL/kg/min) indicated subjects had moderate to severely impaired lower extremity functional performance. The short physical performance battery was related to both 6-minute walk (r = 0.76; P < .0001) and peak fitness (r = 0.52; P < .001). CONCLUSIONS: Our results show that the short physical performance battery may be reflective of endurance-based, longer-distance performance measures that would be difficult to perform in standard clinical stroke settings. Additional studies are needed to explore the value of using the short physical performance battery to assess rehabilitation-related functional progression after stroke.

Interactive Relations of Body Mass Index, Cardiorespiratory Fitness, and Sex to Cognitive Function in Older Adults.

OBJECTIVE: The course of cognitive aging is influenced by multiple health factors. This cross-sectional study investigated the interactive relations between body mass index (BMI), maximum oxygen consumption (VO2max), and sex on neuropsychological outcomes in community-dwelling predominantly older adults. METHODS: Participants were 164 healthy adults [M (SD) = 64.6 (12.5) years, 56% men, 87% white] who participated in an investigation of cardiovascular risk factors and brain health. Multivariable regression analysis, adjusted for age, education, ethnicity, smoking, alcohol consumption, and depression, examined the interactive relations of BMI, VO2max, and sex to multiple neuropsychological outcomes. RESULTS: Significant BMI*VO2max*sex interactions for Grooved Pegboard dominant (p = .019) and nondominant (p = .005) hands revealed that men with lower VO2max (l/min) displayed worse performance with each hand as BMI increased (p's < .02). A significant BMI*sex interaction for Logical Memory-Delayed Recall (p = .036) (after adjustment for blood glucose) showed that men, but not women, with higher BMI demonstrated worse performance (p = .036). Lastly, significant main effects indicated that lower VO2max was related to poorer logical memory, and higher BMI was associated with poorer Trail Making B and Stroop interference scores (p's < .05). CONCLUSIONS: Among men, higher cardiorespiratory fitness may protect against the negative impact of greater BMI on manual dexterity and motor speed, making VO2max a target for intervention. Higher BMI is further associated with poorer executive function and verbal memory (in men), and lower VO2max is associated with poorer verbal memory.

Psychometric limitations of the mini-mental state examination among nondemented older adults: an evaluation of neurocognitive and magnetic resonance imaging correlates.

UNLABELLED: BACKGROUND/STUDY CONTEXT: Although many of the Mini-Mental State Examination's (MMSE) limitations are well accepted among geriatricians, neuropsychologists, and other interested clinicians and researchers, its continued use in psychometrically unsound ways suggests that additional investigation and dissemination of information are sorely needed. The authors aimed to describe the reliability and validity of the MMSE as a measure of cognitive function among healthy older adults. METHODS: The authors examined MMSE performance in 124 stroke- and dementia-free, community-dwelling older adults (65% male; mean age = 66.5 years). All participants were administered an extensive neuropsychological battery composed of measures of attention, executive function, memory, and visuospatial function. A subset of 99 participants also underwent magnetic resonance imaging (MRI). MMSE test-retest reliability was examined among 65 participants who underwent repeat MMSE testing over an average interval of 83.2 days. RESULTS: Spearman test-retest correlation for total MMSE scores was r S = .35 (p = .004), for Serial Sevens was r S = .40 (p = .001), and for Word Recall was r S = -.01 (p = .96). Total MMSE performance correlated significantly with a minority of neuropsychological tests and MRI-derived indices of white matter disease and brain atrophy. A subset of 17% of participants demonstrated inappropriate intrusion of MMSE Pentagon Copy during another test of visuospatial recall. CONCLUSIONS: Overall, MMSE scores exhibited ceiling effects, poor test-retest reliability, limited sensitivity to subtle brain abnormalities, and a high rate of intrusion elsewhere in the neuropsychological battery. Individual MMSE items demonstrated poor construct validity. These qualities illustrate the serious limitations of the MMSE in detecting individual differences in cognitive function among healthy older adults.

Plasma neurofilament light as blood marker for poor brain white matter integrity among middle-aged urban adults.

Plasma neurofilament light chain (NfL)'s link to dementia may be mediated through white matter integrity (WMI). In this study, we examined plasma NfL's relationships with diffusion tensor magnetic resonance imaging markers: global and cortical white matter fractional anisotropy (FA) and trace (TR). Plasma NfL measurements at 2 times (v1: 2004-2009 and v2: 2009-2013) and ancillary dMRI (vscan: 2011-2015) were considered (n = 163, mean time v1 to vscan = 5.4 years and v2 to vscan: 1.1 years). Multivariable-adjusted regression models, correcting for multiple-testing revealed that, overall, higher NfLv1 was associated with greater global TR (ß ± SE: +0.0000560 ± 0.0000186, b = 0.27, p = 0.003, q = 0.012), left frontal WM TR (ß ± SE: + 0.0000706 ± 0.0000201, b ± 0.30, p = 0.001, q = 0.0093) and right frontal WM TR (ß ± SE: + 0.0000767 ± 0.000021, b ± 0.31, p < 0.001, q = 0.0093). These associations were mainly among males and White adults. Among African American adults only, NfLv2 was associated with greater left temporal lobe TR. "Tracking high" in NfL was associated with reduced left frontal FA (Model 2, body mass index-adjusted: ß ± SE:-0.01084 ± 0.00408, p = 0.009). Plasma NfL is a promising biomarker predicting future brain white matter integrity (WMI) in middle-aged adults.

Plasma neurofilament light and brain volumetric outcomes among middle-aged urban adults.

Elevated plasma neurofilament light chain (NfL) is associated with dementia though underlying mechanisms remain unknown. We examined cross-sectional relationships of time-dependent plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia. The sample was drawn from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v1 (2004-2009) and v2 (2009-2013) plasma NfL exposure and ancillary sMRI data at vscan (2011-2015, n = 179, mean v1 to vscan time: 5.4 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, and race, correcting for multiple testing with q-values. NfL(v1) was associated with larger WMLV (both Loge transformed), after 5-6 years' follow-up, overall (ß = +2.131 ± 0.660, b = +0.29, p = 0.001, and q = 0.0029) and among females. NfLv2 was linked to a 125 mm3 lower left hippocampal volume (p = 0.004 and q = 0.015) in reduced models, mainly among males, as was observed for annualized longitudinal change in NfL (δNfLbayes). Among African American adults, NfLv1 was inversely related to total, gray and white matter volumes. Plasma NfL may reflect future brain pathologies in middle-aged adults.

White matter integrity as a mediator between socioeconomic status and executive function.

Introduction: Lower socioeconomic status (SES) is associated with poorer executive function, but the neural mechanisms of this association remain unclear. As healthy brain communication is essential to our cognitive abilities, white matter integrity may be key to understanding socioeconomic disparities. Methods: Participants were 201 African American and White adults (ages 33-72) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) SCAN study. Diffusion tensor imaging was used to estimate regional fractional anisotropy as a measure of white matter integrity. Adjusting for age, analyses examined if integrity of the anterior limb of the internal capsule (ALIC), external capsule (EC), superior longitudinal fasciculus (SLF), and cingulum mediated SES-executive function relations. Results: Lower SES was related to poorer cognitive performance and white matter integrity. Lower Trails B performance was related to poorer integrity of the ALIC, EC, and SLF, and lower Stroop performance was associated with poorer integrity of the ALIC and EC. ALIC mediated the SES-Trails B relation, and EC mediated the SES-Trails B and SES-Stroop relations. Sensitivity analyses revealed that (1) adjustment for race rendered the EC mediations non-significant, (2) when using poverty status and continuous education as predictors, results were largely the same, (3) at least some of the study's findings may generalize to processing speed, (4) mediations are not age-dependent in our sample, and (5) more research is needed to understand the role of cardiovascular risk factors in these models. Discussion: Findings demonstrate that poorer white matter integrity helps explain SES disparities in executive function and highlight the need for further clarification of the biopsychosocial mechanisms of the SES-cognition association.

Association between Physical Activity and Mortality in Patients with Claudication.

PURPOSE: This study aimed to determine the association between light-intensity physical activity and the incidence of all-cause and cardiovascular mortality in patients with peripheral artery disease (PAD) limited by claudication followed for up to 18.7 yr. METHODS: A total of 528 patients with PAD and claudication were screened in Baltimore between 1994 and 2002, and 386 were deemed eligible for the study. At baseline, patients were classified into three physical activity groups: 1) physically sedentary, 2) light intensity, and 3) moderate to vigorous intensity based on a questionnaire. All-cause and cardiovascular mortality of patients through December 2014 was determined using the National Death Index and the U.S. Department of Veterans Affairs and the U.S. Department of Defense Suicide Data Repository. RESULTS: Median survival time was 9.9 yr (interquartile range, 4.9-15.7 yr; range, 0.38-18.7 yr). During follow-up, 257 patients (66.6%) died, consisting of 40/48 (83.3%) from the sedentary group, 135/210 (64.3%) from the light-intensity group, and 82/128 (64.0%) from the moderate- to vigorous-intensity group. For all-cause mortality, light-intensity activity status (hazard ratio [HR] = 0.523, P = 0.0007) and moderate- to vigorous-intensity status (HR = 0.425, P < 0.0001) were significant predictors. During follow-up, 125 patients died because of cardiovascular causes (32.4%), in which light-intensity activity status (HR = 0.511, P = 0.0113) and moderate- to vigorous-intensity activity status (HR = 0.341, P = 0.0003) were significant predictors. CONCLUSIONS: Light-intensity physical activity is associated with nearly 50% lower risk of all-cause and cardiovascular mortality in high-risk patients with PAD and claudication. Furthermore, moderate- to vigorous-intensity physical activity performed regularly is associated with 58% and 66% lower risk of all-cause and cardiovascular mortality, respectively. The survival benefits associated with light-intensity physical activity make it a compelling behavioral intervention that extends beyond improving ambulation.

Corrigendum: Vitamin D, Folate, and Cobalamin Serum Concentrations Are Related to Brain Volume and White Matter Integrity in Urban Adults.

[This corrects the article DOI: 10.3389/fnagi.2020.00140.].

Red Cell Distribution Width, Anemia, and Brain Volumetric Outcomes Among Middle-Aged Adults.

BACKGROUND: Anemia and red cell distribution width (RDW) have been linked to poor cognitive performance, pending studies of underlying mechanisms. OBJECTIVE: We examined cross-sectional relationships of initial RDW status (v1), RDW change (δ), and anemia with brain structural magnetic resonance imaging (sMRI) markers, including global and cortical brain and hippocampal and white matter lesion (WML) volumes, 5-6 years later. METHODS: Data were used from three prospective visits within the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study with complete v1 (2004-2009) and v2 (2009-2013) exposures and ancillary sMRI data at vscan (2011-2015, n = 213, mean v1 to vscan time: 5.7 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, by race, and within non-anemics, correcting for multiple testing with q-values. RESULTS: In minimally adjusted models (socio-demographics and follow-up time), anemiav1 and RDWv1 were consistently associated with smaller bilateral hippocampal volumes overall, and among females (q < 0.05), without significant sex differences. RDWv1 was related to smaller select regional cortical brain gray and white matter volumes in hematological measure-adjusted models; anemiav1 was associated with larger WML volumes only among whites. CONCLUSION: In summary, baseline anemia and RDW were consistently associated with smaller bilateral hippocampal volumes, particularly among females, while anemia was linked to larger WML volume among Whites. In hematological measure-adjusted models, baseline RDW was linked to smaller regional gray and white matter volumes. Pending studies with sMRI repeats, randomized controlled trials are needed, demonstrating associations of anemia and elevated RDW with reduced brain volumes and cognitive dysfunction.

Red cell distribution width, anemia and their associations with white matter integrity among middle-aged urban adults.

Anemia (blood hemoglobin [Hb] <13 g/dL among males; <12 g/dL among females) and elevated red cell distribution width (RDW) are potential risk factors for reduced brain white matter integrity (WMI), reflected by lower fractional anisotropy or increased mean diffusivity. Cross-sectional data with exposure-outcome lag time was used, whereby hematological exposures (RDW and Hb) and covariates were compiled from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study with available visit 1 (v1; 2004-2009) and/or v2 (2009-2013) data; while diffusion tensor magnetic resonance imaging (dMRI) outcome data were collected at HANDLS SCAN visit (vscan: 2011-2015, n = 214, mean follow-up from v1 ±SD: 5.6 ± 1.8 year). Multivariable-adjusted linear regression analyses were conducted, overall, stratifying by sex, and further restricting to the nonanemic for RDW exposures in part of the analyses. Among males, RDW(v1) was linked with lower global mean fractional anisotropy (standardized effect size b = -0.30, p= 0.003, q < 0.05; basic model), an association only slightly attenuated with further covariate adjustment. Anemia was not a risk factor for poor WMI, independently of RDW. Ultimately, pending further longitudinal evidence, initial RDW appears to be associated with poorer WMI among males.