Objective: Locomotor adaptation enables safe, efficient navigation among changing environments. We investigated how healthy young (HYA) and older (HOA) adults and persons with Parkinson's disease (PD) adapt to walking on a split-belt treadmill, retain adapted gait parameters during re-adaptation, and store aftereffects to conventional treadmill walking. Methods: Thirteen PD, fifteen HYA, and fifteen HOA walked on a split-belt treadmill for ten minutes with one leg twice as fast as the other. Participants later re-adapted to the same conditions to assess retention of the split-belt gait pattern. After re-adaptation, we assessed aftereffects of this pattern during conventional treadmill walking. Results: Persons with PD exhibited step length asymmetry throughout many adaptation and adaptive learning conditions. Early adaptation was similar across groups, though HYA and HOA continued to adapt into late adaptation while PD did not. Despite pervasive step length asymmetry among conditions which were symmetric in HYA and HOA, persons with PD demonstrated significant step length aftereffects during conventional treadmill walking after split-belt walking. Conclusions: Though they may exhibit a default asymmetry under various walking conditions, persons with PD can adapt and store new walking patterns. Significance: Locomotor adaptation therapy may be effective in ameliorating asymmetric gait deficits in persons with PD.

Having a healthy sleep pattern plays a vital role in one’s overall health. Sleep in the elderly is characterized by decreased slow-wave sleep and an increase of REM sleep. Furthermore, quantitative electroencephalographic (qEEG) studies have shown an age-related attenuation of total EEG power in sleep. However, exercise has been shown to improve sleep across all age groups. In this study, we used the Sleep Profiler™ EEG Sleep Monitor to observe EEG changes occurring during sleep following an aerobic exercise intervention. This study was done on older adults (N = 18, with only five subjects containing both pre- and post-data of sufficient quality for analysis) with an age range 60–85 years. The aerobics regimen was performed three times weekly for 12-weeks commencing with 20-min sessions. The time of each session progressed by 1–2 min/session as needed to a maximum time of 45 min per session. The macro-architecture (sleep stages) and microarchitecture (EEG) results were analyzed using MATLAB. For the microarchitecture, our results showed more deep sleep following the aerobic exercise regimen. Furthermore, for the microarchitecture, out results shows an increase in total EEG power post-exercise in both light (N1 and L1) and deep sleep (N2 and N3). These preliminary changes in sleep the microarchitecture suggest that non-pharmacologic methods might mitigate age-related EEG changes with potential implications for neurocognitive health.

Previous work has shown that older adults who evidence increased right inferior frontal gyrus (IFG) activity during language tasks show decreased sematic verbal fluency performance. The current study sought to evaluate if an aerobic exercise intervention can alter patterns of brain activity during a semantic verbal fluency task assessed by functional magnetic resonance imaging (fMRI). Thirty-two community-dwelling, sedentary older adults were enrolled to a 12-week aerobic “Spin” exercise group or a 12-week nonaerobic exercise control condition (Balance). Thirty participants completed their assigned intervention (16 Spin; 14 Balance) with pre- and postintervention assessments of a semantic verbal fluency task during fMRI and estimated VO2max testing. There was a significant increase in the change scores for estimated VO2max of the Spin group when compared to the Balance group. Semantic verbal fluency output within the scanner was also improved in the Spin group as compared to controls at postassessment. Group fMRI comparisons of IFG activity showed lower activity in the right IFG following the intervention in the aerobic Spin group when compared to the Balance group. Regression analysis of imaging data with change in both estimated VO2max and semantic verbal fluency was negatively correlated with activity in right IFG. The current work is registered as clinical trial with NCT01787292 and NCT02787655.

In reports of randomized controlled trials, thorough description of the attention control condition has been recommended, yet is frequently lacking. The Tele-Savvy Caregiver program for informal caregivers of persons living with dementia was tested in a randomized controlled trial with an attention control condition. The purpose of this trial was to test Tele-Savvy's efficacy in reducing the negative effects of caregiving on caregivers, promoting quality of life for persons living with dementia, and improving caregiver mastery. We describe the design and implementation of and examine the outcomes associated with the attention control condition. Caregivers were randomized to the immediate Tele-Savvy (active condition), Healthy Living (attention control), or waitlist. The attention control content was focused on healthy lifestyle and was not intended to affect the outcomes that Tele-Savvy targeted. The attention control group was similar to Tele-Savvy in the intervention structure and duration: it consisted of seven weekly group videoconferences and 36 video lessons. Data on outcomes of caregivers and persons living with dementia were collected at baseline and 3 and 6 months postbaseline. Multilevel mixed effects models were used to determine changes in the outcomes. One hundred and eleven caregivers were randomized to the attention control condition (attrition 21.6%). Eighteen formative assessment interviews focusing on caregivers' experience in the attention control condition were conducted. The attention control condition completers had no statistically significant changes in the variables that Tele-Savvy targeted. These results may be used in the design and implementation of attention control conditions in behavioral intervention research.

Background: To date, no medication has slowed the progression of Parkinson’s disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of endurance exercise among persons with PD. The key question is whether there is a definitive additional benefit of exercising at high intensity, in terms of slowing disease progression, beyond the well-documented benefit of endurance training on a treadmill for fitness, gait, and functional mobility. This study will determine the efficacy of high-intensity endurance exercise as first-line therapy for persons diagnosed with PD within 3 years, and untreated with symptomatic therapy at baseline. Methods: This is a multicenter, randomized, evaluator-blinded study of endurance exercise training. The exercise intervention will be delivered by treadmill at 2 doses over 18 months: moderate intensity (4 days/week for 30 min per session at 60–65% maximum heart rate) and high intensity (4 days/week for 30 min per session at 80–85% maximum heart rate). We will randomize 370 participants and follow them at multiple time points for 24 months. The primary outcome is the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor score (Part III) with the primary analysis assessing the change in MDS-UPDRS motor score (Part III) over 12 months, or until initiation of symptomatic antiparkinsonian treatment if before 12 months. Secondary outcomes are striatal dopamine transporter binding, 6-min walk distance, number of daily steps, cognitive function, physical fitness, quality of life, time to initiate dopaminergic medication, circulating levels of C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF). Tertiary outcomes are walking stride length and turning velocity. Discussion: SPARX3 is a Phase 3 clinical trial designed to determine the efficacy of high-intensity, endurance treadmill exercise to slow the progression of PD as measured by the MDS-UPDRS motor score. Establishing whether high-intensity endurance treadmill exercise can slow the progression of PD would mark a significant breakthrough in treating PD. It would have a meaningful impact on the quality of life of people with PD, their caregivers and public health. Trial registration: ClinicalTrials.govNCT04284436. Registered on February 25, 2020.

Subthreshold depressive symptoms are highly prevalent among older adults and are associated with numerous health risks including cognitive decline and decreased physical health. One brain region central to neuroanatomical models of depressive disorders is the anterior cingulate cortex (ACC). The rostral portion of the ACC-comprised of the pregenual ACC and subgenual ACC-is implicated in emotion control and reward processing. The goal of the current study was to examine how functional connectivity in subregions of the rostral ACC relate to depressive symptoms, measured by the Beck Depression Inventory-Second Edition, in an ethnically diverse sample of 28 community-dwelling older adults. Based on meta-analyses of previous studies in primarily young adults with clinical depression, we hypothesized that greater depressive symptoms would be associated with primarily increased resting-state functional connectivity from both the subgenual ACC and pregenual ACC to default mode network regions and the dorsolateral PFC. We instead found that higher depressive symptoms were associated with lower functional connectivity of the ACC to the dorsolateral PFC and regions within the default mode network, including from the subgenual ACC to the dorsolateral PFC and anterior cingulate and from the pregenual ACC to the middle cingulate gyrus. This preliminary study highlights brain alterations at subthreshold levels of depressive symptoms in older adults, which could serve as targets for interventions.

BACKGROUND. Chronic kidney disease (CKD) is characterized by chronic overactivation of the sympathetic nervous system (SNS), which increases the risk of cardiovascular (CV) disease and mortality. SNS overactivity increases CV risk by multiple mechanisms, including vascular stiffness. We tested the hypothesis that aerobic exercise training would reduce resting SNS activity and vascular stiffness in patients with CKD. METHODS. In this randomized controlled trial, sedentary older adults with CKD underwent 12 weeks of exercise (cycling, n = 32) or stretching (an active control group, n = 26). Exercise and stretching interventions were performed 20-45 minutes/session at 3 days/week and were matched for duration. Primary endpoints include resting muscle sympathetic nerve activity (MSNA) via microneurography, arterial stiffness by central pulse wave velocity (PWV), and aortic wave reflection by augmentation index (AIx). RESULTS. There was a significant group × time interaction in MSNA and AIx with no change in the exercise group but with an increase in the stretching group after 12 weeks. The magnitude of change in MSNA was inversely associated with baseline MSNA in the exercise group. There was no change in PWV in either group over the study period. CONCLUSION. Our data demonstrate that 12 weeks of cycling exercise has beneficial neurovascular effects in patients with CKD. Specifically, exercise training safely and effectively ameliorated the increase in MSNA and AIx observed over time in the control group. This sympathoinhibitory effect of exercise training showed greater magnitude in patients with CKD with higher resting MSNA.

Aerobic fitness (AF) and self-reported physical activity (srPA) do not represent the same construct. However, many exercise and brain aging studies interchangeably use AF and srPA measures, which may be problematic with regards to how these metrics are associated with brain outcomes, such as morphology. If AF and PA measures captured the same phenomena, regional brain volumes associated with these measures should directly overlap. This study employed the general linear model to examine the differential association between objectively-measured AF (treadmill assessment) and srPA (questionnaire) with gray matter density (GMd) in 29 cognitively unimpaired community-dwelling older adults using voxel based morphometry. The results show significant regional variance in terms of GMd when comparing AF and srPA as predictors. Higher AF was associated with greater GMd in the cerebellum only, while srPA displayed positive associations with GMd in occipito-temporal, left perisylvian, and frontal regions after correcting for age. Importantly, only AF level, and not srPA, modified the relationship between age and GMd, such that higher levels of AF were associated with increased GMd in older age, while decreased GMd was seen in those with lower AF as a function of age. These results support existing literature suggesting that both AF and PA exert beneficial effects on GMd, but only AF served as a buffer against age-related GMd loss. Furthermore, these results highlight the need for use of objective PA measurement and comparability of tools across studies, since results vary dependent upon the measures used and whether these are objective or subjective in nature.

BACKGROUND: Data are sparse regarding the impacts of habitual physical activity (PA) and sedentary behavior on cardiovascular (CV) risk in older adults with mobility limitations.METHODS AND RESULTS: This study examined the baseline, cross-sectional association between CV risk and objectively measured PA among participants in the Lifestyle Interventions and Independence for Elders (LIFE) study. The relationship between accelerometry measures and predicted 10-year Hard Coronary Heart Disease (HCHD) risk was modeled by using linear regression, stratified according to CVD history. Participants (n=1170, 79±5 years) spent 642±111 min/day in sedentary behavior (ie, <100 accelerometry counts/min). They also spent 138±43 min/day engaging in PA registering 100 to 499 accelerometry counts/min and 54±37 min/day engaging in PA ≥500 counts/min. Each minute per day spent being sedentary was associated with increased HCHD risk among both those with (0.04%, 95% CI 0.02% to 0.05%) and those without (0.03%, 95% CI 0.02% to 0.03%) CVD. The time spent engaging in activities 100 to 499 as well as ≥500 counts/min was associated with decreased risk among both those with and without CVD (P<0.05). The mean number of counts per minute of daily PA was not significantly associated with HCHD risk in any model (P>0.05). However, a significant interaction was observed between sex and count frequency (P=0.036) for those without CVD, as counts per minute was related to HCHD risk in women (β=-0.94, -1.48 to -0.41; P<0.001) but not in men (β=-0.14, -0.59 to 0.88; P=0.704).CONCLUSIONS: Daily time spent being sedentary is positively associated with predicted 10-year HCHD risk among mobility-limited older adults. Duration, but not intensity (ie, mean counts/min), of daily PA is inversely associated with HCHD risk score in this population-although the association for intensity may be sex specific among persons without CVD.CLINICAL TRIAL REGISTRATION URL: www.clinicaltrials.gov Unique identifier: NCT01072500.

This pilot examines whether resistance training (RT) can induce changes in kynurenine (KYN) metabolism, which may contribute to improved physical function in breast cancer survivors (BCSs). Thirty-six BCSs (63.2 ± 1.1 years) underwent assessments of physical function and visual analog scale (100 cm) fatigue and quality of life before and after 12 weeks of RT (N = 22) or non-exercise control (CBCT©: Cognitively Based Compassion Training, N = 10). Blood was collected before and after interventions for assessment of KYN, kynurenic acid (KYNA), and peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α). At baseline, the women were moderately fatigued (mean score: 46 cm) and at risk of poor functional mobility. A group*time interaction was observed for all measures of strength with improvements (~25–35%) following RT (p’s < 0.01), but not CBCT. Time effects were observed for fatigue (−36%) and quality of life (5%) (p’s < 0.01), where both groups improved in a similar manner. A group*time interaction was observed for KYN (p = 0.02) and PGC-1α (p < 0.05), with KYN decreasing and PGC-1α increasing following RT and the opposite following CBCT. These changes resulted in KYN/KYNA decreasing 34% post-RT, but increasing 21% following CBCT. These data support RT as a therapeutic intervention to counteract the long-term side effect of fatigue and physical dysfunction in BCSs. Additionally, the results suggest that this effect may be mediated through the activation of PGC-1α leading to alterations in KYN metabolism.