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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., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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 v 1 (2004-2009) and v 2 (2009-2013) plasma NfL exposure and ancillary sMRI data at v scan (2011-2015, n = 179, mean v 1 to v scan 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 Log e transformed), after 5-6 years' follow-up, overall (β = +2.131 ± 0.660, b = +0.29, p = 0.001, and q = 0.0029) and among females. NfLv 2 was linked to a 125 mm 3 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 (δNfL bayes ). Among African American adults, NfL v1 was inversely related to total, gray and white matter volumes. Plasma NfL may reflect future brain pathologies in middle-aged adults., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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 m 2 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 (Vo 2 peak) 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 m 2 ; 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., (Published by Elsevier Inc.)

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 (v 1 : 2004-2009 and v 2 : 2009-2013) and ancillary dMRI (v scan : 2011-2015) were considered (n = 163, mean time v 1 to v scan  = 5.4 years and v 2 to v scan : 1.1 years). Multivariable-adjusted regression models, correcting for multiple-testing revealed that, overall, higher NfL v1 was associated with greater global TR (β ± SE: +0.0000560 ± 0.0000186, b = 0.27, p = 0.003, q = 0.012), left frontal WM TR (β ± SE: + 0.0000706 ± 0.0000201, b ± 0.30, p = 0.001, q = 0.0093) and right frontal WM TR (β ± 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, NfL v2 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: β ± 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., (Published by Elsevier Inc.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shaked, Katzel, Davatzikos, Gullapalli, Seliger, Erus, Evans, Zonderman and Waldstein.)

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., (Copyright © 2022 by the American Psychosomatic Society.)

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 (v 1 ; 2004-2009) and/or v 2 (2009-2013) data; while diffusion tensor magnetic resonance imaging (dMRI) outcome data were collected at HANDLS SCAN visit (v scan : 2011-2015, n = 214, mean follow-up from v 1 ±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., (Published by Elsevier Inc.)

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 (VO 2 ), peak aerobic capacity (VO 2 peak), 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 VO 2 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, VO 2 peak (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., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to report., (Copyright © 2021. Published by Elsevier Inc.)

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., (Published by Oxford University Press on behalf of the American Academy of Pain Medicine. This work is written by a US Government employee and is in the public domain in the US.)

Objective: Post-traumatic stress disorder (PTSD) is common in Veterans. Symptoms can perpetuate into late life, negatively impacting physical and mental health. Exercise and social support are beneficial in treating anxiety disorders such as PTSD in the general population, although less is known about the impact on Veterans who have lived with PTSD for decades. This study assessed associations between social connectedness, physical function and self-reported change in PTSD symptoms among older Veterans specifically participating in Gerofit., Design: Prospective clinical intervention., Setting: Twelve sites of Veterans Affairs (VA) Gerofit exercise program across the United States., Participants: Three hundred and twenty one older Veteran Gerofit participants (mean age = 74) completed physical assessments and questionnaires regarding physical and emotional symptoms and their experience., Measurements: Measures of physical function, including 30-second chair stands, 10-m and 6-min walk were assessed at baseline and 3 months; change in PTSD symptoms based on the Diagnostic Statistical Manual-5 (DSM-5) assessed by a self-report questionnaire; and social connection measured by the Relatedness Subscale of the Psychological Need Satisfaction in Exercise scale (PNSE) were evaluated after 3 months of participation in Gerofit., Results: Ninety five (29.6%) Veterans reported PTSD. Significant improvement was noted in self-rated PTSD symptoms at 3 months (P < .05). Moderate correlation (r = .44) was found between social connectedness with other participants in Gerofit and PTSD symptom improvement for those Veterans who endorsed improvement (n = 59). All participants improved on measures of physical function. In Veterans who endorsed PTSD there were no significant associations between physical function improvement and PTSD symptoms., Conclusion: Veterans with PTSD that participated in Gerofit group exercise reported symptom improvement, and social connectedness was significantly associated with this improvement. In addition to physical health benefits, the social context of Gerofit may offer a potential resource for improving PTSD symptoms in older Veterans that warrants further study., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

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., (Copyright © 2020 by the American College of Sports Medicine.)

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.

Exercise is critical for health maintenance in late life. The COVID-19 shelter in place and social distancing orders resulted in wide-scale interruptions of exercise therapies, placing older adults at risk for the consequences of decreased mobilization. The purpose of this paper is to describe rapid transition of the Gerofit facility-based group exercise program to telehealth delivery. This Gerofit-to-Home (GTH) program continued with group-based synchronous exercise classes that ranged from 1 to 24 Veterans per class and 1 to 9 classes offered per week in the different locations. Three hundred and eight of 1149 (27%) Veterans active in the Gerofit facility-based programs made the transition to the telehealth delivered classes. Participants' physical performance testing continued remotely as scheduled with comparisons between most recent facility-based and remote testing suggesting that participants retained physical function. Detailed protocols for remote physical performance testing and sample exercise routines are described. Translation to remote delivery of exercise programs for older adults could mitigate negative health effects., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Purpose of Review: Frailty is characterized by decreased physiological reserve and increased risk of falls, disability, hospitalization, and mortality. Frail older adults may benefit from exercise interventions targeting their multiple problems and functional deficits; however, most research focuses on center-based interventions, which may present accessibility challenges for frail older adults. Therefore, the purpose of this review is to summarize the most recently published home-based exercise interventions for frail older adults living at home., Recent Findings: Eight manuscripts met inclusion criteria. Research interventions consisted of a variety of modes (strength, strength/nutrition, strength/flexibility/balance/endurance), duration (12 weeks to 6 months), frequency (2-7 days/week), and delivery methods (volunteer-led, videos on a tablet, manuals/brochures). Investigators examined the effects of home-based exercise on a variety of outcomes to include feasibility, frailty status, physical performance, lean body mass, skeletal muscle mass, other physiological outcomes, mental health, nutritional status, and incidence of falls in frail., Summary: This review demonstrates the feasibility and effectiveness of home-based exercise interventions to improve frailty, functional performance, nutritional status, and incidence of falls in frail older adults. However, the limited literature available provides conflicting reports regarding benefits for mental health outcomes and no evidence of a beneficial effect on skeletal muscle or lean mass. Future research is needed to shed light on the optimal components of home exercise programs most important for maximizing benefits for frail older adults, as well as the most effective delivery method., Competing Interests: Conflict of Interest No conflicts of interest to report. All procedures performed in these studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

The Stroop Color and Word Test is a test of processing speed, response inhibition, and executive functioning (EF). This project examined whether extending the Stroop Color-Word trial beyond the standard time limit could more accurately assess performance on EF measures. Cognitively healthy older individuals ( n  = 198) enrolled in a study of cardiovascular health completed the Stroop as part of a neuropsychological battery. Two scores were computed for the Color-Word trial: the number of items completed within the first 45 seconds (traditional Color-Word score) and the speed of page completion beyond the first 45 seconds (Stroop-Extended score). Criterion measures included the Trail-Making Test Part B (TMT-B), Digit Span Backward, Symbol Digit Modalities Test, Short Category Test, and measures of verbal fluency. Results from hierarchical linear regression analyses indicated that the extended Stroop score accounted for small but statistically significant variance in TMT-B (additional 2.6%) and Digit Span Backwards (additional 2.6%) beyond the standard Color-Word score. These findings suggest that extending the Stroop Color-Word trial beyond the first 45 seconds provides a limited increase in predictive power within a healthy sample with restricted range of performance. The extended Stroop requires additional examination in heterogeneous samples, including clinical populations, to determine its predictive utility.

Concentrations of different circulating microparticles (MPs) may have clinical and physiological relevance to cardiovascular disease pathologies., Purpose: To quantify plasma concentrations of CD31+/CD42b-, CD62E+, and CD34+ MPs across healthy individuals and those with coronary artery disease (CAD) or acute cardiovascular events (non-ST elevation myocardial infarction (NSTEMI)). Fasted blood was obtained from CAD patients (n = 10), NSTEMI patients (n = 13), and healthy older men (n = 15) 60-75 years old., Methods: CD31+/CD42b-, CD62E+, and CD34+ MPs were isolated from plasma and quantified using flow cytometry. Relationships between MP subtypes, fasting blood lipids, blood glucose, blood pressure, body mass index, and total number of medications were assessed., Results: Concentrations of CD31+/CD42b- MPs were significantly lower in CAD and NSTEMI subjects compared with healthy individuals (p = .02 and .003, respectively). No differences between groups were found for CD62E+ or CD34+ MPs (p > .05 for both). Surprisingly, among all variables assessed, only CD62E+ MP concentrations were positively correlated with triglyceride levels (p = .012) and inversely correlated with SBP (p = .03)., Conclusions: Our findings provide support for the use of different MP subtypes, specifically CD31+/CD42b- MPs, as a potential biomarker of cardiovascular disease. Importantly, results from this study should be looked at in adjunct to previous MP work in CVD conditions as a way of highlighting the complex interactions of variables such as comorbid conditions and medications on MP concentrations., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objectives: Previous studies in older adults found robust associations between executive functions (EF) and physical performance, as well as sociodemographic variation in physical performance decline. To examine these associations earlier in the adult lifespan, we investigated relations of EF, race, and sex with age-related physical performance decline during middle adulthood., Method: Participants were 2,084 urban-dwelling adults (57.2% female; 57.8% African American; 37.3% living in poverty; mean baseline age = 48.1) from the Healthy Aging in Neighborhoods of Diversity across the Life Span study. Mixed-effects regression was used to examine interactive relations among EF, race, sex, and age (indexing time) with change in dominant and nondominant handgrip strength and lower extremity strength over approximately 5 years. All analyses adjusted for poverty status, and subsequently adjusted for education, body mass index, hypertension, and diabetes., Results: There were no significant prospective associations between EF and decline in physical performance measures. Significant cross-sectional associations revealed that lower EF was associated with worse performance on all physical performance measures averaged across both time points (p < .05). A significant two-way interaction of Sex × Age (p = .019) revealed that men experienced greater age-related decline in lower extremity strength than women., Discussion: Findings did not reveal prospective associations between EF and physical performance decline in middle adulthood. However, they identified robust cross-sectional associations between EF and physical performance, and unexpectedly greater decline in lower extremity strength in men than women. Ultimately, these findings may inform prevention and intervention strategies targeting groups at risk for poorer physical function status and decline., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and objectives: Lower vitamin status has been linked to cognitive deficits, pending mechanistic elucidation. Serum 25-hydroxyvitamin D [25(OH)D], folate and cobalamin were explored against brain volumes and white matter integrity (WMI). Methods: Three prospective waves from Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study were used [Baltimore, City, MD, 2004-2015, N = 183-240 urban adults (Age v1 : 30-64 years)]. Serum vitamin 25-hydroxyvitamin D [25(OH)D], folate and cobalamin concentrations were measured at visits 1 (v 1 : 2004-2009) and 2 (v 2 : 2009-2013), while structural and diffusion Magnetic Resonance Imaging (sMRI/dMRI) outcomes were measured at v scan : 2011-2015. Top 10 ranked adjusted associations were corrected for multiple testing using familywise Bonferroni (FWER <0.05) and false discovery rates (FDR, q -value < 0.10). Results: We found statistically significant (FWER < 0.05; β±SE) direct associations of 25(OH)D(v 1 ) with WM volumes [overall: +910 ± 336/males: +2,054 ± 599], occipital WM; [overall: +140 ± 40, males: +261 ± 67 and Age v1 > 50 years: +205 ± 54]; parietal WM; [overall: +251 ± 77, males: +486 ± 129 and Age v1 > 50 years: +393 ± 108] and left occipital pole volume [overall: +15.70 ± 3.83 and above poverty: 19.0 ± 4.3], findings replicated for 25(OH)D (v 2 -v 1 ) annualized exposure, which was also linked with greater WMI (fractional anisotropy, FA) in the anterior limb of the internal capsule (ALIC); FWER < 0.05 [Overall: +0.0020 ± 0.0004; Whites: +0.0024 ± 0.0004] and in the cingulum (hippocampus) [Overall: +0.0016 ± 0.0004]. Only trends were detected for cobalamin exposures ( q < 0.10), while serum folate (v 1 ) was associated with lower mean diffusivity (MD) in ALIC, reflecting greater WMI, overall. Conclusions: Among urban adults, serum 25(OH)D status and increase were consistently linked to larger occipital and parietal WM volumes and greater region-specific WMI. Pending longitudinal replication of our findings, randomized controlled trials of vitamin D supplementation should be conducted against brain marker outcomes., (Copyright © 2020 Beydoun, Shaked, Hossain, Beydoun, Katzel, Davatzikos, Gullapalli, Seliger, Erus, Evans, Zonderman and Waldstein.)

Heart rate variability (HRV) is a noninvasive tool used to evaluate autonomic nervous system function and is affected by age, stress, postural changes, and physical activity. Dog ownership has been associated with higher 24-hr HRV and increased physical activity compared to nonowners. The current pilot study was designed to evaluate the effects of proximity to a dog in real time (minute-by-minute) on older dog caregivers' HRV measures and stress index during normal daily life over a 24-hr period. Eleven caregivers (56-83 years of age) wore ActiGraph GT9X Link accelerometers and camntech electrocardiogram monitors, and 11 dogs wore PetPace Collars and ActiGraph monitors to determine (a) proximity (absence or presence of Received Signal Strength Indicator, RSSI), (b) heart rate and HRV measures, (c) position (lying vs. sitting vs. standing), and (d) physical activity in the 11 dyads. Twenty-four hour HRV (SDNN index) and physical activity in the caregivers and dogs were related. Stress index was lower, and HRV parameters (SDNN, rMSDD, high frequency power (HF)) were higher when an RSSI signal was detected (presence of dog) compared to no RSSI signal (absence of dog) in the caregivers while inactive (lying + sitting + standing combined). HRV parameters (rMSDD and HF) were lower in the caregivers while standing and sitting compared to lying. The results from this pilot study support the hypothesis that spending time in the presence of a companion dog increases caregivers' HRV throughout the day and suggest that proximity to a dog may contribute to overall improvements in 24-hr HRV and cardiac health in dog caregivers.

Despite the high prevalence of diastolic dysfunction in adults living with HIV, the impact on cardiorespiratory fitness (CRF) is understudied. The objective of this cross-sectional study was to investigate the relationship between cardiac function and CRF in adults with HIV. Adults receiving antiretroviral therapy with no history of coronary artery disease (CAD) or heart failure were eligible to participate. Cardiac function was assessed by resting Doppler echocardiography. CRF was measured by oxygen utilization at peak exercise (VO 2 peak). The majority of participants were African American (86%) and male (97%) with a mean [standard deviation (SD)] age of 56.6 (7.1) years and median CD4 lymphocyte count of 492 cells/mL. The mean (SD) VO 2 peak was 26.1 (5.5) mL/(kg·min). Age, diabetes, hypertension, and hemoglobin were associated with VO 2 peak. Overall, diastolic dysfunction was present in 38% and was associated with lower VO 2 peak ( p  < 0.05). VO 2 peak was lower among those with impaired myocardial relaxation (e' <8 cm/s) compared with normal relaxation [mean ± SE mL/(kg·min), 25.2 ± 0.6 vs. 27.7 ± 0.9, p  < 0.05]. Adjusted for age and clinical factors, each unit increase in left ventricular relaxation (E/A) was associated with an average 4.4 mL/(kg·min) higher VO 2 peak, representing more than one metabolic equivalent. We conclude that diastolic dysfunction is independently associated with clinically significant low CRF in adults with HIV and no history of CAD or heart failure. These results highlight the importance of recognizing diastolic dysfunction in individuals living with HIV regardless of their cardiovascular disease history.

There is a growing literature demonstrating a link between lower socioeconomic status (SES) and poorer neuroanatomical health, such as smaller total and regional gray and white matter volumes, as well as greater white matter lesion volumes. Little is known, however, about the relation between SES and white matter integrity. Here we examined the relation between SES and white matter integrity of the brain's primary cortical regions, and evaluated potential moderating influences of age and self-identified race. Participants were 192 neurologically intact, community-dwelling African American and White adults (mean age = 52 years; 44% male, 60% White, low SES = 52%) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) SCAN study. Participants underwent 3.0-T cranial magnetic resonance imaging. Diffusion tensor imaging was used to estimate regional fractional anisotropy (FA) to quantify the brain's white matter integrity and trace to capture diffusivity. Multiple regression analyses examined independent and interactive associations of SES, age, and race with FA of the frontal, temporal, parietal, and occipital lobes bilaterally. Sensitivity analyses assessed the influence of several biopsychosocial risk factors on these associations. Exploratory analyses examined these relations with trace and using additional SES indicators. Results indicated there were no significant interactions of SES, age, and race for any region. Individuals with low SES had lower FA in all regions, and higher trace in the right and left frontal, right and left temporal, and left occipital lobes. Findings remained largely unchanged after inclusion of sensitivity variables. Older age was associated with lower FA and greater trace for all regions, except for the right temporal lobe with FA. No main effects were found for race in FA, and Whites had higher trace values in the parietal lobes. Novel findings of this study indicate that relative to the high SES group, low SES was associated with poorer white matter integrity and greater diffusivity. These results may, in part, reflect exposures to various biopsychosocial risk factors experienced by those of lower SES across the lifespan, and may help explain the preponderance of cognitive and functional disparities between socioeconomic groups.

This study sought to examine the interactive relations of socioeconomic status and race to corticolimbic regions that may play a key role in translating stress to the poor health outcomes overrepresented among those of lower socioeconomic status and African American race. Participants were 200 community-dwelling, self-identified African American and White adults from the Healthy Aging in Neighborhoods of Diversity across the Life Span SCAN study. Brain volumes were derived using T1-weighted MP-RAGE images. Socioeconomic status by race interactions were observed for right medial prefrontal cortex (B = .26, p = .014), left medial prefrontal cortex (B = .26, p = .017), left orbital prefrontal cortex (B = .22, p = .037), and left anterior cingulate cortex (B = .27, p = .018), wherein higher socioeconomic status Whites had greater volumes than all other groups. Additionally, higher versus lower socioeconomic status persons had greater right and left hippocampal (B = -.15, p = .030; B = -.19, p = .004, respectively) and amygdalar (B = -.17, p = .015; B = -.21; p = .002, respectively) volumes. Whites had greater right and left hippocampal (B = -.17, p = .012; B = -.20, p = .003, respectively), right orbital prefrontal cortex (B = -.34, p < 0.001), and right anterior cingulate cortex (B = -.18, p = 0.011) volumes than African Americans. Among many factors, the higher levels of lifetime chronic stress associated with lower socioeconomic status and African American race may adversely affect corticolimbic circuitry. These relations may help explain race- and socioeconomic status-related disparities in adverse health outcomes., Competing Interests: The authors have declared that no competing interests exist.

Objective: Studies have linked self-reported discrimination to telomere attrition, a biological marker of accelerated cellular aging. However, it is unknown whether intersections between social categories-race, socioeconomic status (SES), sex, and age-influence the association of varying forms of discrimination with telomere length. We examined these associations in a socioeconomically and racially/ethnically diverse urban sample., Methods: Cross-sectional data were from 341 middle-aged (30-64 years) African American and White, community participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span Study (HANDLS). Multiple regression models examined up to 3-way interactions between a discrimination measure (i.e., everyday, racial, gender, lifetime burden, and frequency of discrimination across sources) and two social categories., Results: After adjusting for depressive symptoms, waist circumference, and lifetime substance use, two themes emerged: 1) among women with higher SES, a) greater lifetime discrimination burden (b = -0.23, p =  .011), gender discrimination (b = -0.29, p =  .040), and racial discrimination (b = -0.24, p = 0.023) and 2) among younger adults, irrespective of race and sex, greater frequency of discrimination across sources (b = 0.002, p =  .008) was associated with shorter telomeres., Conclusions: Irrespective of race, women with higher SES and younger adults reporting greater discrimination may be at particular risk for accelerated aging. Telomere attrition promotes and accelerates chronic health conditions for which there are health disparities. Future research explicating intersections among specific discrimination indices and social categories is warranted., (Copyright © 2018. Published by Elsevier B.V.)

Objective: Explore interactive relations of lifetime discrimination burden and racial discrimination-chronic stressors among African Americans (AAs)-and age with MRI-assessed white matter lesion volume (WMLV), a prognostic indicator of poor clinical brain health outcomes., Method: AAs (N = 71; 60.6% female, mean age = 50) participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) SCAN study underwent quantitative magnetic resonance imaging coded for WMLV. Participants self-reported lifetime discrimination burden and racial discrimination approximately 5 years earlier. Multivariable regression models assessed interactions of linear and quadratic effects of discrimination and age with WMLV adjusted for sex and socioeconomic status., Results: Findings revealed significant interactive relations of age and (a) quadratic, lifetime discrimination burden, B = .05, p = .014, ηpartial2 = .092, and (b) quadratic, racial discrimination, B = .03, p = .001, ηpartial2 = .155, with WMLV. Among older AA, increases in lifetime discrimination burden and racial discrimination were associated with increases in WMLV (ps < .03); in younger AA, decreasing levels of racial discrimination were related to increases in WMLV (p = .006)., Conclusions: Among older AA, as lifetime discrimination burden and racial discrimination increased, so did WMLV. However, in younger AA, decreases in racial discrimination were associated with increased WMLV. Elucidation of complex mechanistic underpinnings, including potentially differential impacts of the acknowledgment versus suppression or underreporting of discriminatory experiences, among AA of different age cohorts, is critical to understanding the present pattern of findings. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Previous research has demonstrated inverse associations between experiences of interpersonal discrimination and telomere length, a marker of cellular aging. Here, we investigate within-race interactions between multiple indices of interpersonal discrimination and sociodemographic characteristics in relation to telomere length in African American and White adults. Participants were from the Healthy Aging in Neighborhoods of Diversity across the Life Span study (Baltimore, Maryland). Ages ranged from 30 to 64 years old and all self-identified as either African American (n = 176) or White (n = 165). Using linear regression, three patterns were observed within African Americans: (1) women reporting greater lifetime burden of discrimination (p = .02), racial (p = .03), or gender (p = .01) discrimination; (2) those with higher socioeconomic status reporting greater lifetime burden (p = .03) or racial discrimination (p = .02); and (3) younger adults reporting greater exposure to multiple sources of discrimination (p = .03) had shorter telomere length. Among Whites, younger and older men reporting greater racial discrimination had shorter and longer telomeres, respectively (p = .02). Findings demonstrate within-race patterns of interpersonal discrimination and cellular aging, which may contribute to racial health disparities., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Lower socioeconomic status (SES) is related to poorer cognitive performance, but the neural underpinnings of this relation are not fully understood. This study examined whether SES-linked decrements in executive function were mediated by smaller dorsolateral prefrontal cortex (DLPFC) volumes. Given the literature demonstrating that SES-brain relations differ by race, we examined whether race moderated these mediations., Method: Participants were 190 socioeconomically diverse, self-identified African American (AA) and White adults from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) SCAN study. Regional brain volumes were derived using T1-weighted MP-RAGE images. Adjusting for age and sex, moderated mediation analyses examined if the DLPFC mediated SES-executive function relations differently across racial groups. Executive function was measured using Trail Making Test part B (Trails B), Digit Span Backwards (DSB), and verbal fluency., Results: Moderated mediation demonstrated that DLPFC volume significantly mediated the association between SES and Trails B in Whites (lower confidence interval [CI] = 0.01; upper CI = 0.07), but not in AAs (lower CI = -0.05; upper CI = 0.01). No mediations were found for DSB or verbal fluency, although SES was related to all tests., Conclusion: The DLPFC may be important in the association of SES and mental flexibility for White, but not AA adults. It is possible that the well-replicated advantages of high SES among Whites do not readily translate, on average, to AAs. These findings highlight the importance of brain volume for cognitive functioning, while adding to the literature on sociodemographic health disparities. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Background: HIV-infected adults have increased risk for age-related diseases and low cardiorespiratory fitness that can be prevented and improved with exercise. Yet, exercise strategies have not been well studied in older adults with HIV and may require substantial adaptation to this special population., Objective: To determine the safety and efficacy of aerobic exercise in older HIV-infected men in a randomized trial comparing different levels of exercise intensity., Methods: We conducted a pilot exercise trial in 22 HIV-infected men ≥50 years of age receiving antiretroviral therapy who were randomized 1:1 to moderate-intensity aerobic exercise (Mod-AEX) or high-intensity aerobic exercise (High-AEX) that was performed three times weekly for 16 weeks in a supervised setting. Primary outcome was cardiorespiratory fitness (VO2peak) measured by treadmill testing. Secondary outcomes were exercise endurance, six-minute walk distance (6-MWD), body composition measured by Dual-energy X-ray absorptiometry (DXA), and fasting plasma levels of lipids and glucose., Results: VO2peak increased in the High-AEX group (3.6 ±1.2 mL/kg/min, p = 0.02) but not in the Mod-AEX group (0.4 ±1.4 mL/kg/min, p = 0.7) with a significant between group difference (p<0.01). Exercise endurance increased in both the High-AEX group (27 ±11%, p = 0.02) and the Mod-AEX group (11 ±4%, p = 0.04). The 6-MWD increased in both the High-AEX (62 ±18m, p = 0.01) and the Mod-AEX group (54 ±14m, p = 0.01). Changes in VO2peak and 6-MWD were clinically relevant. There were no serious exercise-related adverse events. Dropouts were similar between group (27% overall) and were related to joint pain., Conclusions: This pilot exercise trial demonstrates that moderate to high-intensity aerobic exercise in older HIV-infected men increases endurance and ambulatory function. However, increased cardiorespiratory fitness was observed only with high-intensity aerobic exercise despite substantial baseline impairment. Future research is needed to determine exercise strategies in older HIV-infected adults that address advanced aging and comorbidity yet are durable and feasible., Competing Interests: The authors have declared that no competing interests exist.

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/m 2 ; 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/height 2 . 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., (Published by Elsevier Inc.)

Background and Purpose: Both obesity and peripheral artery disease (PAD) limit function and may work additively to reduce mobility. The purpose of this study was to compare the effects of a 6-month, center-based walking program on mobility function between adults who are weight-stable obese and nonobese with PAD., Methods: This is a secondary data analysis of 2 combined studies taken from previous work. Fifty-three adults with PAD and intermittent claudication participated in 6 months of treadmill training or standard of care. Patients were divided into 4 groups for analyses: exercise nonobese (Ex), exercise obese (ExO), standard-of-care nonobese (SC), and standard-of-care obese (SCO). Mobility was assessed by a standardized treadmill test to measure claudication onset time (COT) and peak walking time (PWT) as well as the distance walked during a 6-minute walk distance (6MWD) test., Results: There was a significant (P < .001) interaction (intervention × obesity) effect on 6MWD, wherein both exercise groups improved (Ex = 7%, ExO = 16%; P < .02), the SC group did not change (0.9%; P > .05), and the SCO group tended to decline (-18%; P = .06). Both exercise intervention groups significantly improved COT (Ex = 92%, ExO = 102%; P < .01) and PWT (Ex = 54%, ExO = 103%; P < .001). There was no change (P > .05) in either standard-of-care group., Conclusions: Individuals who are obese and nonobese with PAD made similar improvements after a 6-month, center-based walking program. However, patients who are obese with PAD and do not exercise may be susceptible to greater declines in mobility. Exercise may be particularly important in patients who are obese with PAD to avoid declines in mobility.

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.

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 (VO 2 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 VO 2 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., (Published by Elsevier Inc.)

Objective: Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery., Method: Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed and dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as <70 vs. 70+) as an effect modifier., Results: A significant quadratic effect of Total Cholesterol² × Age was identified for Logical Memory II ( b = -.0013, p = .039), such that the 70+ group performed best at high and low levels of total cholesterol than at midrange total cholesterol (U-shaped) and the <70 group performed worse at high and low levels of total cholesterol than at midrange total cholesterol (inverted U shape). Similarly, significant U- and J-shaped effects of LDL Cholesterol² × Age were identified for Visual Reproduction II ( b = -.0020, p = .026) and log of the Trail Making Test, Part B (b = .0001, p = .044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant., Conclusions: Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Background: Skeletal muscle capillary rarefaction limits the transcapillary transport of nutrients and oxygen to muscle and may contribute to sarcopenia and functional impairment in older adults. We tested the hypothesis that skeletal muscle capillarization and exercise capacity (VO2max) are lower in sarcopenic than in nonsarcopenic older adults and that the degree of sarcopenia is related to lower skeletal muscle capillarization., Methods: Body composition, VO2max, and vastus lateralis capillarization were determined in 76 middle-aged and older men and women (age = 61±1 years, body mass index [BMI] = 30.7±0.5kg/m(2) [mean ± SEM]). Participants were classified as sarcopenic if appendicular lean mass divided by BMI (ALMBMI) was less than 0.789 for men or less than 0.512 for women., Results: Sarcopenic subjects (ALMBMI = 0.65±0.04, n = 16) had 20% lower capillary-to-fiber ratio, as well as 13% and 15% lower VO2max expressed as mL/kg/min or L/min, respectively, compared with sex-, race-, and age-matched participants without sarcopenia (ALMBMI = 0.81±0.05, n = 16; p < .05). In all 76 subjects, ALMBMI, thigh muscle cross-sectional area, and VO2max correlated directly with capillarization (r = .30-.37, p ≤ .05), after accounting for age, sex, and race., Conclusions: These findings suggest that low skeletal muscle capillarization is one factor that may contribute to sarcopenia and reduced exercise capacity in older adults by limiting diffusion of substrates, oxygen, hormones, and nutrients. Strategies to prevent the aging-related decline in skeletal muscle capillarization may help to prevent or slow the progression of sarcopenia and its associated functional declines in generally healthy older adults., (Published by Oxford University Press on behalf of the Gerontological Society of America 2016.)

Hypertension confers increased risk for cognitive decline, dementia, and cerebrovascular disease. These associations have been attributed, in part, to cerebral hypoperfusion. Here we posit that relations of higher blood pressure to lower levels of cerebral perfusion may be potentiated by a prior head injury. Participants were 87 community-dwelling older adults - 69% men, 90% white, mean age=66.9years, 27.6% with a history of mild traumatic brain injury (mTBI) defined as a loss of consciousness ≤30min resulting from an injury to the head, and free of major medical (other than hypertension), neurological or psychiatric comorbidities. All engaged in clinical assessment of systolic and diastolic blood pressure (SBP, DBP) and single photon emission computed tomography (SPECT). Computerized coding of the SPECT images yielded relative ratios of blood flow in left and right cortical and select subcortical regions. Cerebellum served as the denominator. Sex-stratified multiple regression analyses, adjusted for age, education, race, alcohol consumption, smoking status, and depressive symptomatology, revealed significant interactions of blood pressure and head injury to cerebral blood flow in men only. Specifically, among men with a history of head injury, higher systolic blood pressure was associated with lower levels of perfusion in the left orbital (β=-3.21, p=0.024) and left dorsolateral (β=-2.61, p=0.042) prefrontal cortex, and left temporal cortex (β=-3.36, p=0.014); higher diastolic blood pressure was marginally associated with lower levels of perfusion in the left dorsolateral prefrontal cortex (β=-2.79, p=0.051). Results indicate that men with a history of head injury may be particularly vulnerable to the impact of higher blood pressure on cerebral perfusion in left anterior cortical regions, thus potentially enhancing risk for adverse brain and neurocognitive outcomes., (Published by Elsevier B.V.)

Aging is associated with a decline in maximal aerobic capacity (VO 2max ) that may be attenuated by chronic endurance exercise. This case study chronicles the changes in marathon times in a 91 year old man who completed 627 marathons and 117 ultramarathons over 42 years. He began running marathons at age 48. His yearly best times remained fairly constant at ~240 minutes from age 50 - 64 years and then gradually rose to about 260 minutes in his early seventies followed by a curvilinear deterioration as he approached his ninth decade. His times plateaued at ~ 600 minutes in his late eighties. Between ages 68 and 89 his VO 2max declined from 43 to 20 ml/kg/min. His marathon times were highly correlated with his VO 2max (r 2 =0.87). The decline in marathons times and VO 2max may reflect the contributions of biological aging, changes in exercise training volume and intensity, injuries, and comorbid disease.

Introduction: Significant evidence has demonstrated that Type 2 diabetes mellitus and related precursors are associated with diminished neurocognitive function and risk of dementia among older adults. However, very little research has examined relations of glucose regulation to neurocognitive function among older adults free of these conditions. The primary aim of this investigation was to examine associations among fasting glucose, glucose tolerance, and neurocognitive function among nondiabetic older adults. The secondary aim was to examine age, gender, and education as potential effect modifiers., Method: The study employed a cross-sectional, correlational study design. Participants were 172 older adults with a mean age of 64.43 years (SD = 13.09). The sample was 58% male and 87% White. Participants completed an oral glucose tolerance test as part of a larger study. Trained psychometricians administered neuropsychological tests that assessed performance in the domains of response inhibition, nonverbal memory, verbal memory, attention and working memory, visuoconstructional abilities, visuospatial abilities, psychomotor speed and executive function, and motor speed and manual dexterity. Linear multiple regressions were run to test study aims., Results: No significant main effects of fasting glucose and 2-hour glucose emerged for performance on any neurocognitive test; however, significant interactions were present. Higher fasting glucose was associated with poorer short-term verbal memory performance among men, but unexpectedly better response inhibition and long-term verbal memory performance for participants over age 70. Higher 2-hour glucose values were associated with reduced divided attention performance among participants with less than a high school education., Conclusions: Mixed findings suggest that glucose levels may be both beneficial and deleterious to neurocognition among nondiabetic older adults. Additional studies with healthy older adults are needed to confirm this unexpected pattern of associations; however, findings have implications for the importance of maintaining healthy glucose levels in older adulthood.

The purpose of this study was to determine the effects of 6-month aerobic exercise training + weight loss (AEX + WL) on basal and insulin activation of glycogen synthase, basal citrate synthase activity, and Akt and AS160 phosphorylation in older, overweight/obese insulin-resistant men (n = 14; 63 ± 2 years; body mass index, 32 ± kg/m(2)). Muscle samples of the vastus lateralis were collected before and during a 3-hour 80 mU/m(2)/min hyperinsulinemic-euglycemic clamp. AEX + WL increased VO2max by 11% (p < .05) and decreased body weight (-9%, p < .001). AEX + WL increased basal citrate synthase activity by 46% (p < .01) and insulin activation of independent (2.9-fold) and fractional (2.3-fold) activities (both p < .001) of glycogen synthase. AEX + WL had no effect on phosphorylation of Akt or AS160. Glucose utilization (M) improved 25% (p < .01), and the change tended to be related to the increase in insulin activation of glycogen synthase fractional activity (r = .50, p = .08) following AEX + WL. In summary, AEX + WL has a robust effect on insulin activation of skeletal muscle glycogen synthase activity that likely contributes to improved glucose utilization in older insulin-resistant men., (© The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To examine how fasting glucose and glucose tolerance are related to magnetic resonance imaging-assessed indicators of subclinical cerebrovascular disease and brain atrophy and their variation according to age, sex and education., Methods: Participants in the present study were 172 healthy, community-dwelling older adults. An oral glucose tolerance test was administered and magnetic resonance imaging performed. Fasting, 2-h, and 2-h area-under-the-curve glucose levels, their associations with subclinical cerebrovascular disease and brain atrophy, and their respective interactions with age, sex and education were examined., Results: A positive association between fasting glucose and subclinical cerebrovascular disease (but not brain atrophy) emerged; this association was more pronounced for participants with < 12 years of education; however, glucose tolerance was not related to subclinical cerebrovascular disease or brain atrophy., Conclusions: Findings revealed a potential link between fasting glucose levels and the presence of subclinical cerebrovascular disease indicators - white matter hyperintensities and silent brain infarction - in older adults without diabetes and with an education level below high school. Additional research is needed to confirm these associations and to determine the need for interventions aimed at closely monitoring and preventing elevated glucose levels in this population to reduce the prevalence of subclinical cerebrovascular disease., (© 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.)

Objective: Transcapillary transport of insulin is one determinant of glucose uptake by skeletal muscle; thus, a reduction in capillary density (CD) may worsen insulin sensitivity. Skeletal muscle CD is lower in older adults with impaired glucose tolerance (IGT) compared with those with normal glucose tolerance and may be modifiable through aerobic exercise training and weight loss (AEX+WL). We tested the hypothesis that 6-month AEX+WL would increase CD to improve insulin sensitivity and glucose tolerance in older adults with IGT., Research Design and Methods: Sixteen sedentary, overweight-obese (BMI 27-35 kg/m2), older (63 ± 2 years) men and women with IGT underwent hyperinsulinemic-euglycemic clamps to measure insulin sensitivity, oral glucose tolerance tests, exercise and body composition testing, and vastus lateralis muscle biopsies to determine CD before and after 6-month AEX+WL., Results: Insulin sensitivity (M) and 120-min postprandial glucose (G120) correlated with CD at baseline (r = 0.58 and r = -0.60, respectively, P < 0.05). AEX+WL increased maximal oxygen consumption (VO2max) 18% (P = 0.02) and reduced weight and fat mass 8% (P < 0.02). CD increased 15% (264 ± 11 vs. 304 ± 14 capillaries/mm(2), P = 0.01), M increased 21% (42.4 ± 4.0 vs. 51.4 ± 4.3 µmol/kg FFM/min, P < 0.05), and G120 decreased 16% (9.35 ± 0.5 vs. 7.85 ± 0.5 mmol/L, P = 0.008) after AEX+WL. Regression analyses showed that the AEX+WL-induced increase in CD independently predicted the increase in M (r = 0.74, P < 0.01) as well as the decrease in G120 (r = -0.55, P < 0.05)., Conclusions: Six-month AEX+WL increases skeletal muscle CD in older adults with IGT. This represents one mechanism by which AEX+WL improves insulin sensitivity in older adults with IGT.

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., (Published by Elsevier Inc.)

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.

Purpose: Impaired economy of gait, prevalent in chronic stroke secondary to residual gait deficits, is associated with intolerance for performing activities of daily living. Gait economy/efficiency is traditionally assessed by determining the rate of oxygen consumption during submaximal treadmill walking. However, the mechanics and energetics of treadmill versus overground walking are very different in stroke survivors with ambulatory deficits. Clearly, overground cardiopulmonary measures are needed to accurately profile movement economy after stroke. An obstacle to obtaining such measures after stroke has been the absence of reliable portable metabolic monitoring equipment. The purpose of this study was to establish the test-retest reliability of a portable metabolic monitoring device during overground walking in hemiparetic stroke survivors., Methods: Twenty-three chronic hemiparetic stroke survivors underwent two 6-minute walk tests while wearing a COSMED K4b(2) portable metabolic measurement system. Intraclass correlations coefficients (ICC) were calculated for both cardiopulmonary parameters and distance covered to determine test-retest reliability. An ICC of ≥ 0.85 was considered reliable., Results: ICCs for relative Vo2 (0.90), absolute Vo2 (0.93), Vco2 (0.93), and minute ventilation (0.95) demonstrated high reliability, but not for heart rate (0.76) or respiratory exchange ratio (0.64). There was no significant difference in the distance each participant walked between the first and second tests, eliminating distance as a potential confounder of our analyses (ICC = 0.99)., Conclusions: Our results strongly support the reliability of the K4b(2) for quantifying overground gait efficiency after stroke. Use of this device may enable researchers to study how varying poststroke rehabilitation interventions affect this central measure of health and function.

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.

Objective: To compare the efficacy of treadmill exercises and stretching and resistance exercises in improving gait speed, strength, and fitness for patients with Parkinson disease., Design: A comparative, prospective, randomized, single-blinded clinical trial of 3 types of physical exercise., Setting: The Parkinson's Disease and Movement Disorders Center at the University of Maryland and the Baltimore Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center., Patients: A total of 67 patients with Parkinson disease who had gait impairment were randomly assigned to 1 of 3 arms of the trial. INTERVENTIONS; (1) A higher-intensity treadmill exercise (30 minutes at 70%-80% of heart rate reserve), (2) a lower-intensity treadmill exercise (50 minutes at 40%-50% of heart rate reserve), and (3) stretching and resistance exercises (2 sets of 10 repetitions on each leg on 3 resistance machines [leg press, leg extension, and curl]). These exercises were performed 3 times a week for 3 months., Main Outcome Measures: The primary outcome measures were gait speed (6-minute walk), cardiovascular fitness (peak oxygen consumption per unit time [$$ VO2], and muscle strength (1-repetition maximum strength)., Results: All 3 types of physical exercise improved distance on the 6-minute walk: lower-intensity treadmill exercise (12% increase; P=.001), stretching and resistance exercises (9% increase; P<.02), and higher-intensity treadmill exercise (6% increase; P=.07), with no between-group differences. Both treadmill exercises improved peak $$ VO2 (7%-8% increase; P<.05) more than did the stretching and resistance exercises. Only stretching and resistance improved muscle strength (16% increase; P<.001)., Conclusions: The effects of exercise were seen across all 3 exercise groups. The lower-intensity treadmill exercise resulted in the greatest improvement in gait speed. Both the higher- and lower-intensity treadmill exercises improved cardiovascular fitness. Only the stretching and resistance exercises improved muscle strength. Therefore, exercise can improve gait speed, muscle strength, and fitness for patients with Parkinson disease. The combination of treadmill and resistance exercises may result in greater benefit and requires further investigation.

The Judgment of Line Orientation (JLO) test is a commonly used measure of visuospatial perception. Because of its length, several short forms have appeared in the literature. We examined the internal consistency of the JLO and eight of its published short forms among 128 undergraduates, 203 healthy older adults, and 55 chronic kidney disease patients. The full test demonstrated good reliability for traditional neuropsychological assessment, but the majority of short forms were adequate only for screening purposes, where greater measurement error is typically permitted in exchange for brevity. In contrast, a recently developed short form based upon item response theory demonstrated promise as a stand-alone measure.

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.