Peripheral Vascular Function in Stroke: Systematic Review and Meta-Analysis.

Peripheral vascular dysfunction, measured as flow-mediated dilation (FMD), is present across all phases of stroke recovery and elevates risk for recurrent cardiovascular events. The objective of this systematic review and meta-analysis was to characterize baseline FMD in individuals post-stroke, with consideration for each phase of stroke recovery. METHODS: Three databases (PubMed, CINAHL, and Embase) were searched between January 1st, 2000 and October 12th, 2023 for studies that examined baseline FMD in stroke. Three reviewers conducted abstract and full-text screening, data extraction, and quality assessment. A random effects model was used to estimate FMD across studies. Meta-regression was used to the examine impact of age and time since stroke (acute, subacute, chronic) on FMD. RESULTS: Twenty-eight studies with ischemic and hemorrhagic stroke were included. Descriptive statistics for the demographics and FMD values of each study are presented. For the meta-analysis, average estimate FMD was 3.9% (95% CI: 2.5-5.3%). We report a large amount of heterogeneity (Cochrane's Q p-value <0.001, and I2 = 99.6%). Differences in average age and the time post-stroke between studies was not significantly associated with differences in FMD values. CONCLUSION: Despite the large heterogeneity for FMD values across studies, our primary finding suggests that FMD remains impaired across all phases of stroke.

Blood Pressure Variability and Autonomic Response to an Acute Bout of High Intensity Interval Exercise in Healthy Young Adults.

Autonomic nervous system (ANS) activity causes acute variations in the blood pressure. Blood pressure responds to high intensity interval exercise (HIIE) repeatedly during alternating intensities, however, ANS response to the changing intensities of HIIE is unknown. We characterized the response of beat-to-beat blood pressure variability (BTB BPV) to an acute bout of HIIE using coefficient of variation (CoV) and spectral low frequency [LF], and high frequency [HF] domains. Our hypotheses were mean arterial pressure BTB BPV, would increase during 1) high intensity and 2) active recovery of HIIE compared to baseline (BL). BTB BPV would reduce during 1) cool down 2) post HIIE 3) 30 minutes post HIIE compared to BL in young adults. HIIE included bouts of 1-minute high-intensity separated by 1-minute recovery (□70% and 10% estimated Wattmax) for total of 10 minutes on a recumbent stepper. A secondary analysis was performed using twenty-one datasets of young individuals (age 25±1.5, 48% female). During high intensity, LF and HF increased compared to BL (p < 0.05) indicating increased sympathetic activity and breathing. During active recovery, LF and HF remained elevated above BL and were greater than during high intensity (p ≤ 0.02). Sympathetic activity reduced back to BL immediately post HIIE but returned to being higher than BL at 30 minutes after HIIE (p=0.001). BTB BPV CoV also increased during HIIE compared to BL (p<0.05). Results suggest that young healthy individuals have increased BTB BPV during HIIE suggesting cardiovascular system responds to ANS fluctuations during changing exercise intensity. New and Noteworthy: This novel study analyzed beat -to-beat blood pressure variability during high intensity interval exercise (HIIE) in young healthy adults. We found that blood pressure variability was highest during active recovery compared to resting or high intensity exercise. Moreover, variability increased during HIIE but returned to resting post-exercise. These findings provide valuable insights into the blood pressure and ANS responses to HIIE, contributing to our understanding of their impact on overall cardiovascular health in young adults.

Lower dynamic cerebral autoregulation following acute bout of low-volume high-intensity interval exercise in chronic stroke compared to healthy adults.

Fluctuating arterial blood pressure during high-intensity interval exercise (HIIE) may challenge dynamic cerebral autoregulation (dCA), specifically after stroke after an injury to the cerebrovasculature. We hypothesized that dCA would be attenuated at rest and during a sit-to-stand transition immediately after and 30 min after HIIE in individuals poststroke compared with age- and sex-matched control subjects (CON). HIIE switched every minute between 70% and 10% estimated maximal watts for 10 min. Mean arterial pressure (MAP) and middle cerebral artery blood velocity (MCAv) were recorded. dCA was quantified during spontaneous fluctuations in MAP and MCAv via transfer function analysis. For sit-to-stand, time delay before an increase in cerebrovascular conductance index (CVCi = MCAv/MAP), rate of regulation, and % change in MCAv and MAP were measured. Twenty-two individuals poststroke (age 60 ± 12 yr, 31 ± 16 mo) and twenty-four CON (age 60 ± 13 yr) completed the study. Very low frequency (VLF) gain (P = 0.02, η2 = 0.18) and normalized gain (P = 0.01, η2 = 0.43) had a group × time interaction, with CON improving after HIIE whereas individuals poststroke did not. Individuals poststroke had lower VLF phase (P = 0.03, η2 = 0.22) after HIIE compared with CON. We found no differences in the sit-to-stand measurement of dCA. Our study showed lower dCA during spontaneous fluctuations in MCAv and MAP following HIIE in individuals poststroke compared with CON, whereas the sit-to-stand response was maintained.NEW & NOTEWORTHY This study provides novel insights into poststroke dynamic cerebral autoregulation (dCA) following an acute bout of high-intensity interval exercise (HIIE). In people after stroke, dCA appears attenuated during spontaneous fluctuations in mean arterial pressure (MAP) and middle cerebral artery blood velocity (MCAv) following HIIE. However, the dCA response during a single sit-to-stand transition after HIIE showed no significant difference from controls. These findings suggest that HIIE may temporarily challenge dCA after exercise in individuals with stroke.

A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

RATIONALE: Fatigue affects almost half of all people living with stroke. Stroke survivors rank understanding fatigue and how to reduce it as one of the highest research priorities. METHODS: We convened an interdisciplinary, international group of clinical and pre-clinical researchers and lived experience experts. We identified four priority areas: (1) best measurement tools for research, (2) clinical identification of fatigue and potentially modifiable causes, (3) promising interventions and recommendations for future trials, and (4) possible biological mechanisms of fatigue. Cross-cutting themes were aphasia and the voice of people with lived experience. Working parties were formed and structured consensus building processes were followed. RESULTS: We present 20 recommendations covering outcome measures for research, development, and testing of new interventions and priority areas for future research on the biology of post-stroke fatigue. We developed and recommend the use of the Stroke Fatigue Clinical Assessment Tool. CONCLUSIONS: By synthesizing current knowledge in post-stroke fatigue across clinical and pre-clinical fields, our work provides a roadmap for future research into post-stroke fatigue.

A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

RATIONALE: Fatigue affects almost half of all people living with stroke. Stroke survivors rank understanding fatigue and how to reduce it as one of the highest research priorities. METHODS: We convened an interdisciplinary, international group of clinical and pre-clinical researchers and lived experience experts. We identified four priority areas: (1) best measurement tools for research, (2) clinical identification of fatigue and potentially modifiable causes, (3) promising interventions and recommendations for future trials, and (4) possible biological mechanisms of fatigue. Cross-cutting themes were aphasia and the voice of people with lived experience. Working parties were formed and structured consensus building processes were followed. RESULTS: We present 20 recommendations covering outcome measures for research, development, and testing of new interventions and priority areas for future research on the biology of post-stroke fatigue. We developed and recommend the use of the Stroke Fatigue Clinical Assessment Tool. CONCLUSIONS: By synthesizing current knowledge in post-stroke fatigue across clinical and pre-clinical fields, our work provides a roadmap for future research into post-stroke fatigue.

Staying Strong and Healthy During Androgen Deprivation Therapy.

BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer is associated with cardiovascular comorbidities and numerous adverse effects decreasing health-related quality of life. Both exercise and dietary interventions have shown promise in reducing ADT-related negative sequelae. However, feasibility for personalized combined exercise/nutrition/education interventions is not well established. OBJECTIVE: The purpose of this randomized, controlled, mixed-methods pilot study was to evaluate the feasibility of a nurse-led, telephone-delivered education, exercise, and nutrition intervention, Staying Strong & Healthy, to minimize ADT-related cardiovascular/metabolic risks and symptoms. METHODS: Staying Strong & Healthy involves individually tailored education, exercise (aerobic and resistance), and nutrition intervention delivered over 6 months and was compared with attention control. The primary quantitative outcome measure was change from baseline in low-density lipoprotein. Secondary outcomes included change in lipid levels (total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides), fasting blood glucose, hemoglobin A 1c , health-related quality of life, and diet quality. Assessments were performed at baseline, 6 months, and 12 months. RESULTS: Feasibility was demonstrated by low attrition rates and high participant satisfaction. No between-group differences were demonstrated in the cardiovascular/metabolic outcomes. Significant within-group improvements were noted for high-density lipoprotein and hemoglobin A 1c in the intervention group. CONCLUSION: The study results indicate that participation in a personalized, nurse-delivered exercise, nutrition, and educational intervention is feasible and acceptable to men with prostate cancer receiving ADT. IMPLICATIONS FOR PRACTICE: Future randomized controlled research powered to detect significant differences is needed to confirm the impact of the Staying Strong & Healthy intervention on reduction of the cardiovascular/metabolic impact of ADT for men with prostate cancer.

Biomarker Responses to Acute Exercise and Relationship with Brain Blood Flow.

BACKGROUND: There is evidence that aerobic exercise is beneficial for brain health, but these effects are variable between individuals and the underlying mechanisms that modulate these benefits remain unclear. OBJECTIVE: We sought to characterize the acute physiological response of bioenergetic and neurotrophic blood biomarkers to exercise in cognitively healthy older adults, as well as relationships with brain blood flow. METHODS: We measured exercise-induced changes in lactate, which has been linked to brain blood flow, as well brain-derived neurotrophic factor (BDNF), a neurotrophin related to brain health. We further quantified changes in brain blood flow using arterial spin labeling. RESULTS: As expected, lactate and BDNF both changed with time post exercise. Intriguingly, there was a negative relationship between lactate response (area under the curve) and brain blood flow measured acutely following exercise. Finally, the BDNF response tracked strongly with change in platelet activation, providing evidence that platelet activation is an important mechanism for trophic-related exercise responses. CONCLUSIONS: Lactate and BDNF respond acutely to exercise, and the lactate response tracks with changes in brain blood flow. Further investigation into how these factors relate to brain health-related outcomes in exercise trials is warranted.

Lower middle cerebral artery blood velocity during low-volume high-intensity interval exercise in chronic stroke.

High-intensity interval training (HIIE) may present unique challenges to the cerebrovascular system in individuals post-stroke. We hypothesized lower middle cerebral artery blood velocity (MCAv) in individuals post-stroke: 1) during 10 minutes of HIIE, 2) immediately following HIIE, and 3) 30 minutes after HIIE, compared to age- and sex-matched controls (CON). We used a recumbent stepper submaximal exercise test to determine workloads for high-intensity and active recovery. Our low volume HIIE protocol consisted of 1-minute intervals for 10 minutes. During HIIE, we measured MCAv, mean arterial pressure (MAP), heart rate (HR), and end tidal carbon dioxide (PETCO2). We assessed carotid-femoral pulse wave velocity as a measure of arterial stiffness. Fifty participants completed the study (25 post-stroke, 76% ischemic, 32% moderate disability). Individuals post-stroke had lower MCAv during HIIE compared to CON (p = 0.03), which remained 30 minutes after HIIE. Individuals post-stroke had greater arterial stiffness (p = 0.01) which was moderately associated with a smaller MCAv responsiveness during HIIE (r = -0.44). No differences were found for MAP, HR, and PETCO2. This study suggests individuals post-stroke had a lower MCAv during HIIE compared to their peers, which remained during recovery up to 30 minutes. Arterial stiffness may contribute to the lower cerebrovascular responsiveness post-stroke.

The Association of Tacrolimus Formulation on Cerebral Blood Flow and Cognitive Function.

Calcineurin inhibitors are inherent vasoconstrictors. Cerebral vasoconstriction can reduce cerebral blood flow (CBF), and negatively impact cerebrovascular response (CVR) to exercise, and cognitive function. The once-daily extended-release (LCP) tacrolimus has fewer side effects than the immediate-release (IR) tacrolimus. The role of calcineurin inhibitors on CBF and the impact of specific formulations of tacrolimus on CBF, CVR, and cognitive function are unknown. In this pilot study, we evaluated whether changing from IR tacrolimus to LCP tacrolimus modulates CBF, CVR, or cognitive function in kidney transplant (KT) recipients. Methods: We randomized (2:1) 30 stable KT recipients on IR tacrolimus to intervention (switch to LCP tacrolimus) and control (continue IR tacrolimus) arms. We measured CBF, CVR, and cognitive function at baseline and at 12 wk. We used ANCOVA to evaluate changes in outcome variables, with baseline values and study arm as covariates. We used descriptive statistics with mean changes in outcome variables to compare the 2 groups. Results: Participants were 51 ± 13 y old. There was no difference in plasma tacrolimus levels at baseline and at 12 wk in the 2 arms. The changes in CBF, resting middle cerebral artery velocity, CVR, and cognitive function were more favorable in the intervention arm than in the control group. Conclusions: Changing IR tacrolimus to LCP tacrolimus may improve CBF, cerebrovascular dynamics, and cognitive function in KT recipients. Larger studies are needed to confirm these results.

Aerobic Exercise Improves Cortical Inhibitory Function After Stroke: A Preliminary Investigation.

BACKGROUND AND PURPOSE: Aerobic exercise can elicit positive effects on neuroplasticity and cognitive executive function but is poorly understood after stroke. We tested the effect of 4 weeks of aerobic exercise training on inhibitory and facilitatory elements of cognitive executive function and electroencephalography markers of cortical inhibition and facilitation. We investigated relationships between stimulus-evoked cortical responses, blood lactate levels during training, and aerobic fitness postintervention. METHODS: Twelve individuals with chronic (>6 months) stroke completed an aerobic exercise intervention (40 minutes, 3×/wk). Electroencephalography and motor response times were assessed during congruent (response facilitation) and incongruent (response inhibition) stimuli of a Flanker task. Aerobic fitness capacity was assessed as during a treadmill test pre- and postintervention. Blood lactate was assessed acutely (<1 minute) after exercise each week. Cortical inhibition (N2) and facilitation (frontal P3) were quantified as peak amplitudes and latencies of stimulus-evoked electroencephalographic activity over the frontal cortical region. RESULTS: Following exercise training, the response inhibition speed increased while response facilitation remained unchanged. A relationship between earlier cortical N2 response and faster response inhibition emerged postintervention. Individuals who produced higher lactate during exercise training achieved faster response inhibition and tended to show earlier cortical N2 responses postintervention. There were no associations between and metrics of behavioral or neurophysiologic function. DISCUSSION AND CONCLUSIONS: These preliminary findings provide novel evidence for selective benefits of aerobic exercise on inhibitory control during the initial 4-week period after initiation of exercise training and implicate a potential therapeutic effect of lactate on poststroke inhibitory control.Video Abstract available for more insights from the authors (see the video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A450).

Force sensor reduced measurement error compared with verbal command during sit-to-stand assessment of cerebral autoregulation.

Current methods estimate the time delay (TD) before the onset of dynamic cerebral autoregulation (dCA) from verbal command to stand. A force sensor used during a sit-to-stand dCA measure provides an objective moment an individual stands (arise-and-off, AO). We hypothesized that the detection of AO would improve the accuracy of TD compared with estimation. We measured middle cerebral artery blood velocity (MCAv) and mean arterial pressure (MAP) for 60 s sitting followed by 2-min standing, three times separated by 20 min. TD was calculated as the time from: (1) verbal command and (2) AO, until an increase in cerebrovascular conductance index (CVCi = MCAv/MAP). Sixty-five participants were enrolled: young adults (n = 25), older adults (n = 20), and individuals post-stroke (n = 20). The TD calculated from AO ( x ¯ $$ \overline{x} $$ = 2.98 ± 1.64 s) was shorter than TD estimated from verbal command ( x ¯ $$ \overline{x} $$ = 3.35 ± 1.72 s, η2 = 0.49, p < 0.001), improving measurement error by ~17%. TD measurement error was not related to age or stroke. Therefore, the force sensor provided an objective method to improve the calculation of TD compared with current methods. Our data support using a force sensor during sit-to-stand dCA measures in adults across the lifespan and post-stroke.

Training parameters and longitudinal adaptations that most strongly mediate walking capacity gains from high-intensity interval training post-stroke.

Background: Locomotor high-intensity interval training (HIIT) has been shown to improve walking capacity more than moderate-intensity aerobic training (MAT) after stroke, but it is unclear which training parameter(s) should be prioritized (e.g. speed, heart rate, blood lactate, step count) and to what extent walking capacity gains are the result of neuromotor versus cardiorespiratory adaptations. Objective: Assess which training parameters and longitudinal adaptations most strongly mediate 6-minute walk distance (6MWD) gains from post-stroke HIIT. Methods: The HIT-Stroke Trial randomized 55 persons with chronic stroke and persistent walking limitations to HIIT or MAT and collected detailed training data. Blinded outcomes included 6MWD, plus measures of neuromotor gait function (e.g. fastest 10-meter gait speed) and aerobic capacity (e.g. ventilatory threshold). This ancillary analysis used structural equation models to compare mediating effects of different training parameters and longitudinal adaptations on 6MWD. Results: Net gains in 6MWD from HIIT versus MAT were primarily mediated by faster training speeds and longitudinal adaptations in neuromotor gait function. Training step count was also positively associated with 6MWD gains, but was lower with HIIT versus MAT, which decreased the net 6MWD gain. HIIT generated higher training heart rate and lactate than MAT, but aerobic capacity gains were similar between groups, and 6MWD changes were not associated with training heart rate, training lactate, or aerobic adaptations. Conclusions: To increase walking capacity with post-stroke HIIT, training speed and step count appear to be the most important parameters to prioritize.

Can mixed circuit training elicit the recommended exercise intensity and energy expenditure in people after stroke?

PURPOSE: To investigate whether mixed circuit training (MCT) elicits the recommended exercise intensity and energy expenditure in people after stroke, and to establish the between-day reproducibility for the percentages of heart rate reserve (%HRR), oxygen uptake reserve (%VO2R), and energy expenditure elicited during two bouts of MCT. METHODS: Seven people aged 58 (12) yr, who previously had a stroke, performed a cardiopulmonary exercise test, a non-exercise control session, and two bouts of MCT. The MCT included 3 circuits of 10 resistance exercises at 15-repetition maximum intensity, with each set of resistance exercise interspersed with 45-s of walking. Expired gases were collected during the MCT and control session and for 40 min afterward. Control session was necessary to calculate the net energy expenditure associated with each bout of MCT. RESULTS: Mean %VO2R (1st MCT: 51.1%, P = .037; 2nd MCT: 54.0%, P = .009) and %HRR (1st MCT: 66.4%, P = .007; 2nd MCT: 67.9%, P = .010) exceeded the recommended minimum intensity of 40%. Both %VO2R (P = .586 and 0.987, respectively) and %HRR (P = .681 and 0.237, respectively) during the 1st and 2nd bouts of MCT were not significantly different to their corresponding gas exchange threshold values derived from cardiopulmonary exercise testing. Mean net total energy expenditure significantly exceeded the minimum recommend energy expenditure in the 1st (P = .048) and 2nd (P = .023) bouts of MCT. Between-day reproducibility for %HRR, %VO2R, and energy expenditure was excellent (ICC: 0.92-0.97). CONCLUSIONS: MCT elicited physiological strain recommended for improving health-related fitness in people after stroke and these responses demonstrated excellent between-day reproducibility.

Optimal Intensity and Duration of Walking Rehabilitation in Patients With Chronic Stroke: A Randomized Clinical Trial.

Importance: For walking rehabilitation after stroke, training intensity and duration are critical dosing parameters that lack optimization. Objective: To assess the optimal training intensity (vigorous vs moderate) and minimum training duration (4, 8, or 12 weeks) needed to maximize immediate improvement in walking capacity in patients with chronic stroke. Design, Setting, and Participants: This multicenter randomized clinical trial using an intent-to-treat analysis was conducted from January 2019 to April 2022 at rehabilitation and exercise research laboratories. Survivors of a single stroke who were aged 40 to 80 years and had persistent walking limitations 6 months or more after the stroke were enrolled. Interventions: Participants were randomized 1:1 to high-intensity interval training (HIIT) or moderate-intensity aerobic training (MAT), each involving 45 minutes of walking practice 3 times per week for 12 weeks. The HIIT protocol used repeated 30-second bursts of walking at maximum safe speed, alternated with 30- to 60-second rest periods, targeting a mean aerobic intensity above 60% of the heart rate reserve (HRR). The MAT protocol used continuous walking with speed adjusted to maintain an initial target of 40% of the HRR, progressing up to 60% of the HRR as tolerated. Main Outcomes and Measures: The main outcome was 6-minute walk test distance. Outcomes were assessed by blinded raters after 4, 8, and 12 weeks of training. Results: Of 55 participants (mean [SD] age, 63 [10] years; 36 male [65.5%]), 27 were randomized to HIIT and 28 to MAT. The mean (SD) time since stroke was 2.5 (1.3) years, and mean (SD) 6-minute walk test distance at baseline was 239 (132) m. Participants attended 1675 of 1980 planned treatment visits (84.6%) and 197 of 220 planned testing visits (89.5%). No serious adverse events related to study procedures occurred. Groups had similar 6-minute walk test distance changes after 4 weeks (HIIT, 27 m [95% CI, 6-48 m]; MAT, 12 m [95% CI, -9 to 33 m]; mean difference, 15 m [95% CI, -13 to 42 m]; P = .28), but HIIT elicited greater gains after 8 weeks (58 m [95% CI, 39-76 m] vs 29 m [95% CI, 9-48 m]; mean difference, 29 m [95% CI, 5-54 m]; P = .02) and 12 weeks (71 m [95% CI, 49-94 m] vs 27 m [95% CI, 3-50 m]; mean difference, 44 m [95% CI, 14-74 m]; P = .005) of training; HIIT also showed greater improvements than MAT on some secondary measures of gait speed and fatigue. Conclusions and Relevance: These findings show proof of concept that vigorous training intensity is a critical dosing parameter for walking rehabilitation. In patients with chronic stroke, vigorous walking exercise produced significant and meaningful gains in walking capacity with only 4 weeks of training, but at least 12 weeks were needed to maximize immediate gains. Trial Registration: ClinicalTrials.gov Identifier: NCT03760016.

Appetite and energy intake following a bout of circuit resistance training in chronic hemiparetic stroke patients: a preliminary randomized controlled trial.

PURPOSE: The main aim of this study was to investigate the effects of circuit resistance training (CRT) on post-exercise appetite and energy intake in chronic hemiparetic stroke patients. A secondary aim was to evaluate the reproducibility of these effects. METHODS: Seven participants met the eligibility criteria and, in a randomized order, participated in a non-exercise control session (CTL) and two bouts of CRT. The CRT involved 10 exercises with 3 sets of 15-repetition maximum per exercise, performed using a vertical loading approach, with each set interspersed with 45s of walking. Expired gases were carried out   to calculate the net energy cost of the exercise and the relative energy intake post-CTL/CRT. Hunger, fullness, desire to eat, and energy intake were assessed at baseline and for 12 h after CTL and CRT. RESULTS: Compared to CTL, hunger, desire to eat (P < .001), and relative energy intake (P < .05) were significantly lower after CRT, whereas the perception of fullness was significantly higher (P < .001). Significant differences between CTL and CRT were observed only for the first 9 h of the post-exercise period for hunger, fullness, and desire to eat (P < .05). No significant differences in appetite or relative energy intake were observed between the two bouts of CRT. CONCLUSIONS: A bout of CRT elicited decreased post-exercise appetite and relative energy intake in chronic hemiparetic stroke patients. Decreased appetite perceptions lasted for around 9 h and were reproducible.

Hippocampal blood flow rapidly and preferentially increases after a bout of moderate-intensity exercise in older adults with poor cerebrovascular health.

Over the course of aging, there is an early degradation of cerebrovascular health, which may be attenuated with aerobic exercise training. Yet, the acute cerebrovascular response to a single bout of exercise remains elusive, particularly within key brain regions most affected by age-related disease processes. We investigated the acute global and region-specific cerebral blood flow (CBF) response to 15 minutes of moderate-intensity aerobic exercise in older adults (≥65 years; n = 60) using arterial spin labeling magnetic resonance imaging. Within 0-6 min post-exercise, CBF decreased across all regions, an effect that was attenuated in the hippocampus. The exercise-induced CBF drop was followed by a rebound effect over the 24-minute postexercise assessment period, an effect that was most robust in the hippocampus. Individuals with low baseline perfusion demonstrated the greatest hippocampal-specific CBF effect post-exercise, showing no immediate drop and a rapid increase in CBF that exceeded baseline levels within 6-12 minutes postexercise. Gains in domain-specific cognitive performance postexercise were not associated with changes in regional CBF, suggesting dissociable effects of exercise on acute neural and vascular plasticity. Together, the present findings support a precision-medicine framework for the use of exercise to target brain health that carefully considers age-related changes in the cerebrovascular system.

Mixed circuit training acutely reduces arterial stiffness in patients with chronic stroke: a crossover randomized controlled trial.

PURPOSE: Investigate whether a single bout of mixed circuit training (MCT) can elicit changes in arterial stiffness in patients with chronic stroke. Second, to assess the between-day reproducibility of post-MCT arterial stiffness measurements. METHODS: Seven participants (58 ± 12 years) performed a non-exercise control session (CTL) and two bouts of MCT on separate days in a randomized counterbalanced order. The MCT involved 3 sets of 15 repetition maximum for 10 exercises, with each set separated by 45-s of walking. Brachial-radial pulse wave velocity (br-PWV), radial artery compliance (AC) and reflection index (RI1,2) were assessed 10 min before and 60 min after CTL and MCT. Ambulatory arterial stiffness index (AASI) was calculated from 24-h recovery ambulatory blood pressure monitoring. RESULTS: Compared to CTL, after 60 min of recovery from the 1st and 2nd bouts of MCT, lower values were observed for br-PWV (mean diff = - 3.9 and - 3.7 m/s, respectively, P < 0.01; ICC2,1 = 0.75) and RI1,2 (mean diff = - 16.1 and - 16.0%, respectively, P < 0.05; ICC2,1 = 0.83) concomitant with higher AC (mean diff = 1.2 and 1.0 × 10-6 cm5/dyna, respectively, P < 0.01; ICC2,1 = 0.40). The 24-h AASI was reduced after bouts of MCT vs. CTL (1st and 2nd bouts of MCT vs. CTL: mean diff = - 0.32 and - 0.29 units, respectively, P < 0.001; ICC2,1 = 0.64). CONCLUSION: A single bout of MCT reduces arterial stiffness during laboratory (60 min) and ambulatory (24 h) recovery phases in patients with chronic stroke with moderate-to-high reproducibility. TRIAL REGISTRATION: Ensaiosclinicos.gov.br identifier RBR-5dn5zd.

Financial Cost Analysis Associated with a Locomotor Exercise Randomized Controlled Trial in Chronic Stroke.

Background: Post-stroke recovery trials pose distinct recruitment and retention challenges, and understanding the financial requirements of conducting randomized controlled trials is crucial to ensure sufficient resources for successful study execution. The purpose of this analysis was to quantify the costs at a single site with a large catchment area of the Moderate-Intensity Exercise Versus High-Intensity Interval Training to Recover Walking Post-Stroke, HIT Stroke Trial. Methods: To determine cost, study expense reports were gathered and divided into four categories: oversight, recruitment, retention, and outcome assessments. Categories were then further divided into chronological order for initial contact and prescreening, consenting, initial screening, and baseline testing. The 12-week intervention was divided into 4-week blocks: intervention block 1, post 4-week outcome testing, intervention block 2, post 8-week outcome testing, intervention block 3, and post 12-week outcome testing. Results: Total direct cost for site execution was $539,768 with cost per participant approximated as $35,984. Oversight costs accounted for 65.8% of the budget at $355,661. To achieve goals related to inclusive participant recruitment ($21,923) and retention ($28,009), our site costs totaled $49,932. Direct study-related costs included screening assessments ($5,905), baseline assessments ($15,028), intervention ($76,952), and outcome assessments ($36,288). Conclusion: Clinical trials on walking rehabilitation and exercise, especially those involving multiple assessment visits, require intensive oversight. This cost analysis provides important and critical insight into the expenses required to successfully execute an exercise-based walking rehabilitation trial in the United States.

Sex Differences in Resilience and Resistance to Brain Pathology and Dysfunction Moderated by Cerebrovascular Response to Exercise and Genetic Risk for Alzheimer's Disease.

Sex as a biological variable appears to contribute to the multifactorial etiology of Alzheimer's disease. We tested sex-based interactions between cerebrovascular function and APOE4 genotype on resistance and resilience to brain pathology and cognitive executive dysfunction in cognitively-normal older adults. Female APOE4 carriers had higher amyloid-ß deposition yet achieved similar cognitive performance to males and female noncarriers. Further, female APOE4 carriers with robust cerebrovascular responses to exercise possessed lower amyloid-ß. These results suggest a unique cognitive resilience and identify cerebrovascular function as a key mechanism for resistance to age-related brain pathology in females with high genetic vulnerability to Alzheimer's disease.

Secondary Analysis of Walking Activities during the Acute Stroke Hospital Stay and Cerebrovascular Health.

Purpose: Physical activity within the hospital post-stroke is recommended for cardiovascular and musculoskeletal health, but no studies have examined cerebrovascular health. We hypothesized individuals who walked farther distances (FARhigh) during the acute phase of stroke recovery in a hospital setting would have a higher resting middle cerebral artery blood velocity (MCAv) and a greater cerebrovascular response (CVR) to moderate-intensity exercise at 3-months post-stroke, compared to individuals who walked shorter distances (FARlow). Methods: At 3-month post-stroke, we recorded 90-seconds of resting baseline (BL) MCAv followed by 6-minutes of moderate-intensity exercise. We calculated CVR as the change in MCAv from BL to steady-state exercise. We retrospectively collected farthest distance walked within the hospital post-stroke from the electronic medical record. Participants were classified as FARhigh or FARlow based on average farthest walking distance. Results: Twenty participants completed the study, age 63 (15) years. BL MCAv was not different between groups (p = 0.07). In comparison to FARlow, we report a higher CVR in FARhigh's ipsilesional ( x ¯ = 7.38 (5.42) vs x ¯ = 2.19 (3.53), p = 0.02) and contralesional hemisphere ( x ¯ = 8.15 (6.37) vs x ¯ = 2.06 (4.76), p = 0.04). Conclusions: Physical activity during the hospital stay post-stroke may support cerebrovascular health after discharge. Prospective studies are needed to support this finding.