Walk with Me Hybrid Virtual/In-Person Walking for Older Adults with Neurodegenerative Disease.

This study presents a protocol for virtual and in-person walking groups for older adults with neurodegenerative diseases and addresses the decline in physical activity and social connectivity during the pandemic. Physical activity, specifically moderate-intensity walking, has been shown to have multiple health benefits for older adults. This methodology was created during the COVID-19 pandemic, contributing to lower physical activity levels and social isolation in older adults. Both the in-person and virtual classes utilize technology such as fitness tracking apps and video platforms. Data are presented from two groups of older adults with neurodegenerative disease: people with prodromal Alzheimer's disease and people with Parkinson's disease. Participants in the virtual classes were screened for balance impairments before the walk, and any person deemed at risk for falls was not eligible to participate virtually. As COVID vaccines became available and restrictions were lifted, in-person walking groups became feasible. Staff and caregivers were trained in balance management, roles/responsibilities, and delivering walking cues. Both walks, virtual and in-person, consisted of a warm up, a walk, and a cool down, and posture, gait, and safety cues were given throughout. Measures of the rate of perceived exertion (RPE) and heart rate (HR) were taken pre-warm up, post-warm up, and at 15 min, 30 min, and 45 min time points. Participants also used a walking application (app) on their phones to record the distance walked and the number of steps taken. The study showed a positive correlation between HR and RPE in both groups. The participants in the virtual group rated the walking group favorably in terms of improving their quality of life during a period of social isolation and contributing to physical, mental, and emotional well-being. The methodology shows a safe and feasible way to implement virtual and in-person walking groups for older adults with neurological diseases.

Exercise modulates sympathetic and vascular function in chronic kidney disease.

BACKGROUNDChronic 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.METHODSIn 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).RESULTSThere 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.CONCLUSIONOur 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.TRIAL REGISTRATIONClinicalTrials.gov, NCT02947750.FUNDINGNIH R01HL135183; NIH R61AT10457; NIH NCATS KL2TR002381; and NIH T32 DK00756; NIH F32HL147547; and VA Merit I01CX001065.

The Relationship Between Resting Cerebral Blood Flow, Neurometabolites, Cardio-Respiratory Fitness and Aging-Related Cognitive Decline.

Older adults typically experience a decline in cognitive function, but improvements in physical health and lifestyle can be neuroprotective across the human lifespan. The primary objective of this study is to advance our basic understanding of how cardiorespiratory fitness and neurophysiological attributes relate to cognitive decline. While cerebral blood flow (CBF) is critical for the supply of nutrients to the tissue, the brain's major neurotransmitters (i.e., gamma-aminobutyric acid, GABA, and glutamate-glutamine complex, Glx) are closely linked to oxidative metabolism. Within the context of flow-metabolism coupling, the critical question is how these neurophysiological parameters interplay, resulting in cognitive decline. Further, how cardiorespiratory fitness may impact aging neurophysiology and cognition is not well understood. To address these questions, we recruited 10 younger and 12 older cognitively intact participants to collect GABA and Glx using magnetic resonance spectroscopy (MRS), CBF using pseudo-continuous arterial spin labeling Magnetic Resonance Imaging (MRI), VO2max as a measure of cardiorespiratory fitness using the YMCA submax test, and cognitive and motor-cognitive measures using a battery of behavioral assessments. We observed expected differences in GABA+, Glx, and CBF between younger and older participants in pre-SMA, a frontal domain-general region. When GABA+ and Glx were related to CBF via multiple linear regression, Glx was identified as the main contributor to the model. For higher-order executive function (i.e., inhibition versus color naming), GABA*Glx*CBF interaction was critical in younger, while only Glx was involved in older participants. For unimanual motor dexterity, GABA*Glx interaction was the common denominator across both groups, but younger participants' brain also engages CBF. In terms of selective motor inhibition, CBF from younger participants was the only major neurophysiological factor. In terms of fitness, cardiorespiratory fitness was significantly related to GABA, Glx, and motor performance when combining cohorts, but no group-specific relationships were observed. Taken together, our results indicate that Glx and CBF coupling decreases with aging, perhaps due to altered glial oxidative metabolism. Our data suggest that GABA, Glx, and CBF are engaged and weighted differently for different cognitive measures sensitized to aging, and higher fitness allows for a more efficient metabolic shift that facilitates improved performance on cognitive-motor tasks.

Aerobic exercise training improves endothelial function and attenuates blood pressure reactivity during maximal exercise in chronic kidney disease.

Patients with chronic kidney disease (CKD) have exaggerated increases in blood pressure during exercise that are associated with endothelial dysfunction. We hypothesized that aerobic exercise training would improve endothelial function and attenuate blood pressure reactivity during exercise in CKD. Sedentary individuals with CKD stages III-IV underwent 12 wk of aerobic cycling exercise (n = 26) or nonaerobic exercise (n = 22, control). Both interventions were performed 3 days/wk and matched for duration. Endothelial function was measured via peripheral arterial tonometry and quantified as reactive hyperemia index (RHI). Peak oxygen uptake (V̇o2peak) was assessed via maximal treadmill exercise testing with concomitant blood pressure monitoring. All measurements were performed at baseline and after the 12-wk intervention. A linear mixed model was used to compare the rate of increase in blood pressure during the test. RHI improved with exercise (Pre = 1.78 ± 0.10 vs. Post = 2.01 ± 0.13, P = 0.03) with no change following stretching (Pre = 1.73 ± 0.08 vs. Post = 1.67 ± 0.10, P = 0.69). Peak systolic blood pressure during the maximal treadmill exercise test was lower after exercise training (Pre = 186 ± 5 mmHg, Post = 174 ± 4 mmHg, P = 0.003) with no change after stretching (Pre = 190 ± 6 mmHg, Post = 190 ± 4 mmHg, P = 0.12). The rate of increase in systolic blood pressure during the V̇o2peak test tended to decrease after training for both groups (-2 mmHg/stage) with no differences between groups (P = 0.97). There was no change in V̇o2peak after either intervention. In conclusion, aerobic exercise training improves endothelial function and attenuates peak blood pressure reactivity during exercise in CKD.NEW & NOTEWORTHY Patients with chronic kidney disease (CKD) exhibit increased blood pressure reactivity during exercise that is associated with endothelial dysfunction. Twelve weeks of structured, aerobic, exercise training improves endothelial function and attenuates peak blood pressure responses during exercise in CKD stages III-IV.

The Effect of Aerobic Exercise on Physical and Cognitive Outcomes in a Small Cohort of Outpatients with Schizophrenia.

BACKGROUND: Schizophrenia (SCZ) is a severe, chronic illness characterized by psychotic symptoms and impairments in many cognitive domains. Dysregulation of brain derived neurotrophic factor (BDNF) is associated with the cognitive impairments seen in patients with SCZ. Given the growing literature supporting a positive effect of aerobic exercise on cognition in other populations, we hypothesized that a structured aerobic exercise program would improve cognitive and functional outcomes in subjects with SCZ, potentially mediated by increases in BDNF. METHODS: The study was a small randomized parallel group clinical trial of subjects with SCZ comparing 12 weeks of aerobic exercise (AE) against control (CON) stretching and balance training. At Baseline, Week 12, and Week 20 we collected serum samples for analysis of brain derived neurotrophic factor (BDNF), and assessed functional, physical, and cognitive outcomes. Linear regression models were used to compare change scores between timepoints. RESULTS: We randomized 21 subjects to AE and 17 to CON; however, only 9 AE and 6 CON completed their programs. Subjects in both groups were slower at the 400 m walk in Week 12 compared to Baseline, but the AE group had significantly less slowing than the CON group (B = -28.32, p = 0.011). Between Week 12 and Week 20, the AE group had a significantly greater change score on the Composite and Visual Learning Domain of the MATRICS Consensus Cognitive Battery (B = 5.11, p = 0.03; B = 13.96, p = 0.006). CONCLUSION: These results indicate that participation in a structured aerobic exercise paradigm may modestly blunt physical function decline and enhance cognitive function in individuals with SCZ.

Correcting Task fMRI Signals for Variability in Baseline CBF Improves BOLD-Behavior Relationships: A Feasibility Study in an Aging Model.

Blood Oxygen Level Dependent (BOLD) functional MRI is a complex neurovascular signal whose magnitude depends on baseline physiological factors such as cerebral blood flow (CBF). Because baseline CBF varies across the brain and is altered with aging, the interpretation of stand-alone aging-related BOLD changes can be misleading. The primary objective of this study was to develop a methodology that combines task fMRI and arterial spin labeling (ASL) techniques to sensitize task-induced BOLD activity by covarying out the baseline physiology (i.e., CBF) in an aging model. We recruited 11 younger and 13 older healthy participants who underwent ASL and an overt language fMRI task (semantic category member generation). We measured in-scanner language performance to investigate the effect of BOLD sensitization on BOLD-behavior relationships. The results demonstrate that our correction approach is effective at enhancing the specificity and sensitivity of the BOLD signal in both groups. In addition, the correction strengthens the statistical association between task BOLD activity and behavioral performance. Although CBF has inherent age dependence, our results show that retaining the age factor within CBF aides in greater sensitization of task fMRI signals. From a cognitive standpoint, compared to young adults, the older participants showed a delayed domain-general language-related task activity possibly due to compromised vessel compliance. Further, assessment of functional evolution of corrected BOLD activity revealed biphasic BOLD dynamics in both groups where BOLD deactivation may reflect greater semantic demand or increased premium on domain general executive functioning in response to task difficulty. Although it was promising to note that the predictability of behavior using the proposed methodology outperforms other methodologies (i.e., no correction and normalization by division), and provides moderate stability and adequate power, further work with a larger cohort and other task designs is necessary to improve the stability of predicting associated behavior. In summary, we recommend correction of task fMRI signals by covarying out baseline CBF especially when comparing groups with different neurovascular properties. Given that ASL and BOLD fMRI are well established and widely employed techniques, our proposed multi-modal methodology can be readily implemented into data processing pipelines to obtain more accurate BOLD activation maps.

Effects of Combined Aerobic Exercise and Cognitive Training on Verbal Fluency in Older Adults.

We have previously shown that aerobic exercise improves measures of verbal fluency in older adults, and such an improvement is correlated with improved cardiovascular reserve (i.e., estimates of VO2). Due to increasing popularity in computer-based cognitive training, we explored whether the addition of cognitive training to aerobic exercise would further enhance the beneficial cognitive impact of exercise. Therefore, this study sought to test the hypothesis that a cognitive training regimen alone would directly improve executive function and that this effect would be potentiated with the addition of aerobic exercise. The interventions lasted 12 weeks, and cognitive assessments were taken immediately prior to and after the interventions. We found that only the groups employing aerobic exercise showed improvements in verbal fluency (semantic and letter) and cardiovascular fitness with no other executive functions being significantly impacted. Cognitive training alone was associated with decreased verbal fluency. These data replicate previous findings which indicate that aerobic exercise may have a remedial or mitigating effect of cognitive decline. In addition, they provide evidence that the addition of concurrent cognitive training to an aerobic exercise program does not provide synergistic improvement in executive functions.

Effects of a 12-Week Aerobic Spin Intervention on Resting State Networks in Previously Sedentary Older Adults.

Objective: We have previously demonstrated that aerobic exercise improves upper extremity motor function concurrent with changes in motor cortical activity using task-based functional magnetic resonance imaging (fMRI). However, it is currently unknown how a 12-week aerobic exercise intervention affects resting-state functional connectivity (rsFC) in motor networks. Previous work has shown that over a 6-month or 1-year exercise intervention, older individuals show increased resting state connectivity of the default mode network and the sensorimotor network (Voss et al., 2010b; Flodin et al., 2017). However, the effects of shorter-term 12-week exercise interventions on functional connectivity have received less attention. Method: Thirty-seven sedentary right-handed older adults were randomized to either a 12-week aerobic, spin cycling exercise group or a 12-week balance-toning exercise group. Resting state functional magnetic resonance images were acquired in sessions PRE/POST interventions. We applied seed-based correlation analysis to left and right primary motor cortices (L-M1 and R-M1) and anterior default mode network (aDMN) to test changes in rsFC between groups after the intervention. In addition, we performed a regression analysis predicting connectivity changes PRE/POST intervention across all participants as a function of time spent in aerobic training zone regardless of group assignment. Results: Seeding from L-M1, we found that participants in the cycling group had a greater PRE/POST change in rsFC in aDMN as compared to the balance group. When accounting for time in aerobic HR zone, we found increased heart rate workload was positively associated with increased change of rsFC between motor networks and aDMN. Interestingly, L-M1 to aDMN connectivity changes were also related to motor behavior changes in both groups. Respective of M1 laterality, comparisons of all participants from PRE to POST showed a reduction in the extent of bilateral M1 connectivity after the interventions with increased connectivity in dominant M1. Conclusion: A 12-week physical activity intervention can change rsFC between primary motor regions and default mode network areas, which may be associated with improved motor performance. The decrease in connectivity between L-M1 and R-M1 post-intervention may represent a functional consolidation to the dominant M1. Topic Areas: Neuroimaging, Aging.

Changes in Cortical Activation Patterns in Language Areas following an Aerobic Exercise Intervention in Older Adults.

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.

Influences of 12-Week Physical Activity Interventions on TMS Measures of Cortical Network Inhibition and Upper Extremity Motor Performance in Older Adults-A Feasibility Study.

Objective: Data from previous cross-sectional studies have shown that an increased level of physical fitness is associated with improved motor dexterity across the lifespan. In addition, physical fitness is positively associated with increased laterality of cortical function during unimanual tasks; indicating that sedentary aging is associated with a loss of interhemispheric inhibition affecting motor performance. The present study employed exercise interventions in previously sedentary older adults to compare motor dexterity and measure of interhemispheric inhibition using transcranial magnetic stimulation (TMS) after the interventions. Methods: Twenty-one community-dwelling, reportedly sedentary older adults were recruited, randomized and enrolled to a 12-week aerobic exercise group or a 12-week non-aerobic exercise balance condition. The aerobic condition was comprised of an interval-based cycling "spin" activity, while the non-aerobic "balance" exercise condition involved balance and stretching activities. Participants completed upper extremity dexterity batteries and estimates of VO2max in addition to undergoing single (ipsilateral silent period-iSP) and paired-pulse interhemispheric inhibition (ppIHI) in separate assessment sessions before and after study interventions. After each intervention during which heart rate was continuously recorded to measure exertion level (load), participants crossed over into the alternate arm of the study for an additional 12-week intervention period in an AB/BA design with no washout period. Results: After the interventions, regardless of intervention order, participants in the aerobic spin condition showed higher estimated VO2max levels after the 12-week intervention as compared to estimated VO2max in the non-aerobic balance intervention. After controlling for carryover effects due to the study design, participants in the spin condition showed longer iSP duration than the balance condition. Heart rate load was more strongly correlated with silent period duration after the Spin condition than estimated VO2. Conclusions: Aging-related changes in cortical inhibition may be influenced by 12-week physical activity interventions when assessed with the iSP. Although inhibitory signaling is mediates both ppIHI and iSP measures each TMS modality likely employs distinct inhibitory networks, potentially differentially affected by aging. Changes in inhibitory function after physical activity interventions may be associated with improved dexterity and motor control at least as evidence from this feasibility study show.

Effect of Verb Network Strengthening Treatment (VNeST) in persons with aphasia: extension and replication of previous findings.

PURPOSE: Verb Network Strengthening Treatment (VNeST) is an aphasia treatment that targets verbs (e.g., measure) and their related thematic roles (e.g., carpenter-lumber). Previous studies reported encouraging results in a number of participants using single-subject design with improvements observed on naming, sentence production, and discourse. The purpose of the current study was to conduct a group analysis evaluating the effect of VNeST on similar outcomes. METHOD: A multiple baseline design across participants was conducted with 11 persons with aphasia due to stroke. Wilcoxon signed-ranks tests were used to evaluate potential improvement from pre- to posttreatment and maintenance. Individual effect sizes were also calculated to evaluate magnitude of change within and across participants. RESULTS: Results showed significant improvement at posttreatment and maintenance on trained and untrained sentence probes and object and action naming. Improvement in the production of sentences not targeted in treatment was nonsignificant at posttreatment assessment but significant at maintenance. Moderate increases in percentage of complete utterances and overall informativeness were observed on discourse. CONCLUSION: The results of this study replicate previous findings and provide evidence that VNeST may promote specific and generalized lexical retrieval abilities and affect basic syntax production in both constrained and discourse production tasks.