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.

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.

Statin contribution to middle cerebral artery blood flow velocity in older adults at risk for dementia.

PURPOSE: It is plausible that statins could improve cerebral blood flow through pleiotropic mechanisms. The purpose of this investigation was to assess the contribution of statins to cerebrovascular variables in older adults with dyslipidemia and familial history of dementia. Furthermore, we explored the interaction between statin use and sex due to prevalent bias in statin trials. METHODS: Middle cerebral artery blood flow velocity (MCAv) was measured using transcranial Doppler ultrasound. Continuous supine rest recordings lasted 8 min. Participants included in analyses were statin (n = 100) or non-statin users (n = 112). RESULTS: MCAv and cerebrovascular conductance were significantly higher in statin users (p = 0.047; p = 0.04), and pulsatility index (PI) was significantly lower in statin users (p < 0.01). An interaction effect between statin use and sex was present for PI (p = 0.02); female statin users had significantly lower cerebrovascular resistance than the other three groups. CONCLUSION: In this cross-sectional analysis, statin use was positively associated with cerebrovascular variables in older adults at risk for dementia. Female statin users had significantly higher resting MCAv and cerebrovascular conductance than female non-statin users. The greatest contribution of statin use was the association with reduced cerebrovascular resistance. Given that cerebrovascular dysregulation is one of the earliest changes in Alzheimer's disease and related dementia pathology, targeting the cerebrovasculature with statins may be a promising prevention strategy.

Sex-specific effects of cardiorespiratory fitness on age-related differences in cerebral hemodynamics.

There is a positive association between cardiorespiratory fitness and cognitive health, but the interaction between cardiorespiratory fitness and aging on cerebral hemodynamics is unclear. These potential interactions are further influenced by sex differences. The purpose of this study was to determine the sex-specific relationships between cardiorespiratory fitness, age, and cerebral hemodynamics in humans. Measurements of unilateral middle cerebral artery blood velocity (MCAv) and cerebral pulsatility index obtained using transcranial Doppler ultrasound and cardiorespiratory fitness [maximal oxygen consumption (V̇o2max)] obtained from maximal incremental exercise tests were retrieved from study records at three institutions. A total of 153 healthy participants were included in the analysis (age = 42 ± 20 yr, range = 18-83 yr). There was no association between V̇o2max and MCAv in all participants (P = 0.20). The association between V̇o2max and MCAv was positive in women, but no longer significant after age adjustment (univariate: P = 0.01; age-adjusted: P = 0.45). In addition, there was no association between V̇o2max and MCAv in men (univariate: P = 0.25, age-adjusted: P = 0.57). For V̇o2max and cerebral pulsatility index, there were significant negative associations in all participants (P < 0.001), in men (P < 0.001) and women (P < 0.001). This association remained significant when adjusting for age in women only (P = 0.03). In summary, higher cardiorespiratory fitness was associated with a lower cerebral pulsatility index in all participants, and the significance remained only in women when adjusting for age. Future studies are needed to determine the sex-specific impact of cardiorespiratory fitness improvements on cerebrovascular health.NEW & NOTEWORTHY We present data pooled from three institutions to study the impact of age, sex, and cardiorespiratory fitness on cerebral hemodynamics. Cardiorespiratory fitness was positively associated with middle cerebral artery blood velocity in women, but not in men. Furthermore, cardiorespiratory fitness was inversely associated with cerebral pulsatility index in both men and women, which remained significant in women when adjusting for age. These data suggest a sex-specific impact of cardiorespiratory fitness on resting cerebral hemodynamics.

Novel application of a force sensor during sit-to-stands to measure dynamic cerebral autoregulation onset.

Current sit-to-stand methods measuring dynamic cerebral autoregulation (dCA) do not capture the precise onset of the time delay (TD) response. Reduced sit-to-stand reactions in older adults and individuals post-stroke could inadvertently introduce variability, error, and imprecise timing. We applied a force sensor during a sit-to-stand task to more accurately determine how TD before the onset of dCA may be altered. Middle cerebral artery blood velocity (MCAv) and mean arterial pressure (MAP) were measured during two sit-to-stands separated by 15 min. Recordings started with participants sitting on a force-sensitive resistor for 60 s, then asked to stand for 2 min. Upon standing, the force sensor voltage immediately dropped and marked the exact moment of arise-and-off (AO). Time from AO until an increase in cerebrovascular conductance (CVC = MCAv/MAP) was calculated as TD. We tested the sensor in four healthy young adults, two older adults, and two individuals post-stroke. Healthy young adults stood quickly and the force sensor detected a small change in TD compared to classically estimated AO, from verbal command to stand. When compared to the estimated AO, older adults had a delayed measured AO and TD decreased up to ~53% while individuals post-stroke had an early AO and TD increased up to ~14%. The stance time during the sit-to-stand has the potential to influence the TD before the onset of dCA metric. As observed in the older adults and participants with stroke, this response may drastically vary and influence TD.

Cerebrovascular response to an acute bout of low-volume high-intensity interval exercise and recovery in young healthy adults.

High-intensity interval exercise (HIIT) is performed widely. However, there is a gap in knowledge regarding the acute cerebrovascular response to low-volume HIIT. Our objective was to characterize the middle cerebral artery blood velocity (MCAv) response during an acute bout of low-volume HIIT in young healthy adults. We hypothesized that MCAv would decrease below the baseline (BL), 1) during HIIT, 2) immediately following HIIT, and 3) 30 min after HIIT. As a secondary objective, we investigated sex differences in the MCAv response during HIIT. Twenty-four young healthy adults completed HIIT [12 males, age = 25 (SD = 2)]. HIIT included 10 min of 1-min high intensity (∼70% estimated maximal Watts) and active recovery (10% estimated maximal Watts) intervals on a recumbent stepper. MCAv, mean arterial pressure (MAP), heart rate (HR), and end-tidal carbon dioxide ([Formula: see text]) were recorded at BL, during HIIT, immediately following HIIT, and 30 min after HIIT. Contrary to our hypothesis, MCAv remained above BL during HIIT. MCAv peaked at minute 3 then decreased concomitantly with [Formula: see text]. MCAv was lower than BL immediately following HIIT (P < 0.001). Thirty minutes after HIIT, MCAv returned to BL (P = 0.47). Compared with men, women had a higher MCAv at BL (P = 0.001), during HIIT (P = 0.009), immediately following HIIT (P = 0.004), and 30 min after HIIT (P = 0.001). MCAv did not decrease below BL during low-volume HIIT. However, MCAv decreased below BL immediately following HIIT and returned to resting values 30 min after HIIT. MCAv also differed between sexes.NEW & NOTEWORTHY We are the first, to our knowledge, to characterize the cerebrovascular and hemodynamic response to low-volume high-intensity interval exercise (HIIT, 1-min intervals) in young healthy adults. Middle cerebral artery blood velocity (MCAv) decreased during the HIIT bout and rebounded during active recovery. Women demonstrated a significantly higher resting MCAv than men and the difference remained during HIIT. Here, we report a novel protocol and characterized the MCAv response during an acute bout of low-volume HIIT.

Postconcussion Exercise Volume Associations With Depression, Anxiety, and Dizziness Symptoms, and Postural Stability: Preliminary Findings.

OBJECTIVE: To examine the association between postconcussion exercise volume and changes in depression, anxiety, dizziness, and postural stability. DESIGN: Secondary analysis of a single-site prospective clinical trial. SETTING: Cerebrovascular research laboratory. PARTICIPANTS: Participants completed questionnaires and underwent tests of gait and balance within 2 weeks of a concussion (mean = 11 ± 3 days postconcussion) and approximately 1 month later (mean = 41 ± 7 days postconcussion). Exercise volume was tracked by weekly exercise logs. INTERVENTIONS: On the basis of a previous work classifying exercise volume following concussion, we grouped participants according to self-reported exercise volume between visits as high exercise volume (≥150 min/wk) or low exercise volume (<150 min/wk). MAIN OUTCOME MEASURES: Participants completed assessments evaluating anxiety and depression (Hospital Anxiety and Depression Scale), dizziness (Dizziness Handicap Inventory), and postural stability (tandem gait and modified Balance Error Scoring System). RESULTS: Thirty-eight participants completed the study, of which 22 were in the high exercise volume group (mean = 71 ± 40 min/wk; 16.8 ± 2.1 years; 59% female) and 16 were in the low exercise volume group (mean = 379 ± 187 min/wk; 17.5 ± 2.1 years; 31% female). Although depression symptoms were not significantly different initially (mean difference = 1.5; 95% CI, -0.68 to 3.68; P = .24), the high exercise volume group had significantly lower depression symptom scores at follow-up (mean difference = 3.0; 95% CI, 1.40 to 4.47; P < .001). Anxiety symptoms (mean difference = 2.8; 95% CI, 0.3 to 5.4; P = 0.03), dizziness symptoms (mean difference = 10.9; 95% CI, 0.2 to 21.5; P = .047), single-task tandem gait (mean difference = 3.1 seconds; 95% CI, 0.2 to 6.0; P = .04), and dual-task tandem gait (mean difference = 4.2 seconds; 95% CI, 0.2 to 8.2; P = .04) were significantly better among the high exercise volume group. CONCLUSION: Greater exercise volumes were associated with lower depression, anxiety, and dizziness symptoms, and faster tandem gait performance. These preliminary findings suggest a potentially beneficial role for exercise within several different domains commonly affected by concussion.

Dizziness, Psychosocial Function, and Postural Stability Following Sport-Related Concussion.

OBJECTIVE: To examine if self-reported dizziness is associated with concussion symptoms, depression and/or anxiety symptoms, or gait performance within 2 weeks of postconcussion. DESIGN: Cross-sectional study. SETTING: Research laboratory. PARTICIPANTS: Participants were diagnosed with a concussion within 14 days of initial testing (N = 40). Participants were divided into 2 groups based on their Dizziness Handicap Inventory (DHI) score: 36 to 100 = moderate/severe dizziness and 0 to 35 = mild/no dizziness. INTERVENTIONS: Participants were tested on a single occasion and completed the DHI, hospital anxiety and depression scale (HADS), Patient Health Questionnaire-9 (PHQ-9), and Post-Concussion Symptom Inventory (PCSI). Three different postural control tests were use: modified Balance Error Scoring System, single-/dual-task tandem gait, and a single-/dual-task instrumented steady-state gait analysis. MAIN OUTCOME MEASURES: Comparison of patient-reported outcomes and postural control outcomes between moderate/severe (DHI ≥ 36) and mild/no (DHI < 36) dizziness groups. RESULTS: Participants with moderate/severe dizziness (n = 19; age = 17.1 ± 2.4 years; 63% female) reported significantly higher symptom burden (PSCI: 43.0 ± 20.6 vs 22.8 ± 15.7; P = 0.001) and had higher median HADS anxiety (6 vs 2; P < 0.001) and depression (6 vs 1; P = 0.001) symptom severity than those with no/minimal dizziness (n = 21; age = 16.5 ± 1.9; 38% female). During steady-state gait, moderate/severe dizziness group walked with significantly slower single-task cadence (mean difference = 4.8 steps/minute; 95% confidence interval = 0.8, 8.8; P = 0.02) and dual-task cadence (mean difference = 7.4 steps/minute; 95% confidence interval = 0.7, 14.0; P = 0.04) than no/mild dizziness group. CONCLUSION: Participants who reported moderate/severe dizziness reported higher concussion symptom burden, higher anxiety scores, and higher depression scores than those with no/mild dizziness. Cadence during gait was also associated with the level of dizziness reported.

Association of Hemodynamic and Cerebrovascular Responses to Exercise With Symptom Severity in Adolescents and Young Adults With Concussion.

BACKGROUND AND OBJECTIVES: Aerobic exercise has become a useful method to assist with postconcussion management. Exercise can exacerbate concussion symptoms even when symptoms are not apparent at rest. Few studies have examined the reasons for symptom exacerbation during exercise following a concussion. We had 2 primary objectives: (1) to delineate cardiopulmonary and cerebrovascular responses to exercise in adolescents and young adults with a concussion and healthy controls and (2) to determine the association between cerebrovascular responses and symptom burden. METHODS: We recruited participants with a recent concussion from a sport concussion clinic between September 1, 2018, and February 22, 2020. They were included if their concussion occurred <3 weeks before initial testing and if they were symptomatic at rest. Participants were excluded if they sustained a concussion in the past year (excluding index injury), reported history of neurologic disorders, or were using medications/devices that may alter neurologic function. Participants completed a progressive, symptom-limited, submaximal exercise protocol on a stationary bicycle. We assessed heart rate, blood pressure, fraction of end tidal CO2 (FETCO2), and middle cerebral artery blood flow velocity (CBF) and cerebrovascular function (vasoactivity and autoregulation) at seated rest and during exercise. RESULTS: We conducted 107 exercise tests (40 concussed, 37 healthy participants initially; 30 concussed at follow-up). Concussed participants were tested initially (mean 17.6 ± 2.2 [SD] years of age; 55% female; mean 12.5 ± 4.7 days postconcussion) and again 8 weeks later (mean 73.3 ± 9.5 days postconcussion). Control participants (mean 18.3 ± 2.4 years; 62% female) were tested once. FETCO2 increased throughout the exercise protocol as heart rate increased, reached a plateau, and declined at higher exercise intensities. CO2 explained >25% of the variation in resting CBF (R 2 > 0.25; p < 0.01) in most (73% individuals). Within the concussion group, resting symptom severity and the heart rate at which FETCO2 reached a plateau explained ∼2/3s of variation in exercise-induced symptom exacerbation (R 2 = 0.65; FETCO2 ß = -1.210 ± 0.517 [SE], p < 0.05). There was a moderate, statistically significant relationship between cerebrovascular responses to CO2 at rest (cerebral vasoactivity) and cerebrovascular responses to exercise-induced changes in FETCO2 (R 2 = 0.13, p = 0.01). DISCUSSION: The arterial CO2 response and symptom exacerbation relationship during postconcussion aerobic exercise may be mediated by increased sensitivity of cerebral vasculature to exercise-related increase in CO2.

Executive dysfunction after multiple concussions is not related to cerebrovascular dysfunction.

Objective.We investigated the relation between prior concussion history and working memory (WM), self-reported cognitive symptom burden, and cerebrovascular function in adolescents and young adults (14-21 years old).Approach.We recruited 59 participants, 34 clinically diagnosed with a sports-related concussion and 25 controls. Concussed subjects were studied at baseline (within 28 days of their injury) and eight weeks after, while control subjects only had one assessment. We assessed WM (n-back task up to four-back), and neurovascular coupling (cerebrovascular responses at middle cerebral artery duringn-back tasks) using a transcranial Doppler ultrasonograph.Main results.There was no significant difference in WM between controls and concussed participants (p = 0.402). However, WM capacity was lower in those who had sustained ≥3 concussions (7.1% with WM capacity of four) compared to those with their first ever concussion (33.3%) and controls (28.0%, overallp = 0.025). At the sub-acute point (n = 24), self-reported cognitive symptom burden was mostly resolved in all but two participants. Despite the resolution of symptoms, WM performance was not different eight weeks post injury (p = 0.706). Neurovascular coupling was not different between controls and concussed participants regardless of prior concussion history.Significance. Up to 20% of concussed individuals experience covert sequelae lasting beyond the resolution of self-reported overt symptoms. How a prior history of concussion impacts the potential for sequelae is not well established, and the underlying mechanisms are unknown. Despite no alterations in neurovascular coupling, a history of prior concussion was associated with significant deficits in WM capacity, and lasted beyond self-reported cognitive symptom resolution.

Cerebrovascular Neuroprotection after Acute Concussion in Adolescents.

OBJECTIVE: To assess acute cerebrovascular function in concussed adolescents (14-21 years of age), whether it is related to resting cerebral hemodynamics, and whether it recovers chronically. METHODS: Cerebral vasoreactivity and autoregulation, based on middle cerebral artery blood flow velocity, was assessed in 28 concussed participants (≤14 days of injury) and 29 matched controls. The participants in the concussion group returned for an 8-week follow-up assessment. Over the course of those 8-weeks, participants recorded aerobic exercise frequency and duration. RESULTS: Between groups, demographic, clinical, and hemodynamic variables were not significantly different. Vasoreactivity was significantly higher in the concussed group (p = 0.02). Within the concussed group, 60% of the variability in resting cerebral blood flow velocity was explained by vasoreactivity and two components of autoregulation - falling slope and effectiveness of autoregulation (adjusted R2  = 0.60, p < 0.001). Moreover, lower mean arterial pressure, lower responses to increases in arterial pressure, and lower vasoreactivity were significantly associated with larger symptom burden (adjusted R2  = 0.72, p < 0.01). By the 8-week timepoint, symptom burden, but not vasoreactivity, improved in all but four concussed participants (p < 0.01). 8-week change in vasoreactivity was positively associated with aerobic exercise volume (adjusted R2  = 0.19, p = 0.02). INTERPRETATION: Concussion resulted in changes in cerebrovascular regulatory mechanisms, which in turn explained the variability in resting cerebral blood flow velocity and acute symptom burden. Furthermore, these alterations persisted chronically despite symptom resolution, but was positively modified by aerobic exercise volume. These findings provide a mechanistic framework for further investigation into underlying cerebrovascular related symptomatology. ANN NEUROL 2021;90:43-51.

Influence of Aerobic Exercise Volume on Postconcussion Symptoms.

BACKGROUND: Aerobic exercise has emerged as a useful treatment to improve outcomes among individuals who experience a concussion. However, compliance with exercise recommendations and the effect of exercise volume on symptom recovery require further investigation. PURPOSE: To examine (1) if an 8-week aerobic exercise prescription, provided within 2 weeks of concussion, affects symptom severity or exercise volume; (2) whether prescription adherence, rather than randomized group assignment, reflects the actual effect of aerobic exercise in postconcussion recovery; and (3) the optimal volume of exercise associated with symptom resolution after 1 month of study. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Individuals randomized to an exercise intervention (n = 17; mean age, 17.2 ± 2.0 years; 41% female; initially tested a mean of 11.3 ± 2.8 days after injury) or standard of care (n = 20; mean age, 16.8 ± 2.2 years; 50% female; initially tested a mean of 10.7 ± 3.2 days after injury) completed an aerobic exercise test within 14 days of injury. They returned for assessments 1 month and 2 months after the initial visit. The aerobic exercise group was instructed to exercise 5 d/wk, 20 min/d (100 min/wk), at a target heart rate based on an exercise test at the initial visit. Participants reported their exercise volume each week over the 8-week study period and reported symptoms at each study visit (initial, 1 month, 2 months). Because of low compliance in both groups, there was no difference in the volume of exercise between the 2 groups. RESULTS: There were no significant symptom severity differences between the intervention and standard-of-care groups at the initial (median Post-Concussion Symptom Inventory, 15 [interquartile range = 10, 42] vs 20 [11, 35.5]; P = .26), 1-month (4 [0, 28] vs 5.5 [0.5, 21.5]; P = .96), or 2-month (6.5 [0, 27.5] vs 0 [0, 4]; P = .11) study visits. Exercise volume was similar between groups (median, 115 [54, 225] vs 88 [28, 230] min/wk for exercise intervention vs standard of care; P = .52). Regardless of group, those who exercised <100 min/wk reported significantly higher symptom severity at the 1-month evaluation compared with those who exercised ≥100 min/wk (median, 1.5 [0, 7.5] vs 12 [4, 28]; P = .03). Exercising ≥160 min/wk successfully discriminated between those with and those without symptoms 1 month after study commencement (classification accuracy, 81%; sensitivity, 90%; specificity, 78%). CONCLUSION: Greater exercise volume was associated with lower symptom burden after 1 month of study, and an exercise volume >160 min/wk in the first month of the study was the threshold associated with symptom resolution after the first month of the study. Because our observation on the association between exercise volume and symptom level is a retrospective and secondary outcome, it is possible that participants who were feeling better were more likely to exercise more, rather than the exercise itself driving the reduction in symptom severity.

Effects of age and sex on middle cerebral artery blood velocity and flow pulsatility index across the adult lifespan.

Reduced middle cerebral artery blood velocity (MCAv) and flow pulsatility are contributors to age-related cerebrovascular disease pathogenesis. It is unknown whether the rate of changes in MCAv and flow pulsatility support the hypothesis of sex-specific trajectories with aging. Therefore, we sought to characterize the rate of changes in MCAv and flow pulsatility across the adult lifespan in females and males as well as within specified age ranges. Participant characteristics, mean arterial pressure, end-tidal carbon dioxide, unilateral MCAv, and flow pulsatility index (PI) were determined from study records compiled from three institutional sites. A total of 524 participants [18-90 yr; females 57 (17) yr, n = 319; males 50 (21) yr, n = 205] were included in the analysis. MCAv was significantly higher in females within the second (P < 0.001), fifth (P = 0.01), and sixth (P < 0.01) decades of life. Flow PI was significantly lower in females within the second decade of life (P < 0.01). Rate of MCAv decline was significantly greater in females than males (-0.39 vs. -0.26 cm s-1·yr, P = 0.04). Rate of flow PI rise was significantly greater in females than males (0.006 vs. 0.003 flow PI, P = 0.01). Rate of MCAv change was significantly greater in females than males in the sixth decade of life (-1.44 vs. 0.13 cm s-1·yr, P = 0.04). These findings indicate that sex significantly contributes to age-related differences in both MCAv and flow PI. Therefore, further investigation into cerebrovascular function within and between sexes is warranted to improve our understanding of the reported sex differences in cerebrovascular disease prevalence.NEW & NOTEWORTHY We present the largest dataset (n = 524) pooled from three institutions to study how age and sex affect middle cerebral artery blood velocity (MCAv) and flow pulsatility index (PI) across the adult lifespan. We report the rate of MCAv decline and flow PI rise is significantly greater in females compared with in males. These data suggest that sex-specific trajectories with aging and therapeutic interventions to promote healthy brain aging should consider these findings.

Feasibility of single session high-intensity interval training utilizing speed and active recovery to push beyond standard practice post-stroke.

BACKGROUND: Improvement in overground walking speed reduces dependency and is a central focus in post-stroke rehabilitation. Previous studies have shown that high-intensity interval training (HIT) can significantly improve functional and health-related outcomes in neurologically health individuals more so than traditional approaches. Emerging evidence suggests the same may be true post-stroke. OBJECTIVE: The purpose of this study was to assess the feasibility of a single session, novel HIT design. METHODS: Participants walked on a treadmill, alternating between one minute at high-intensity and one minute at low-intensity for 20 minutes, adjusting the speed of the treadmill to dictate intensity. Treadmill speeds were determined from overground self-selected walking speed (SSWS). RESULTS: No adverse events occurred during the training sessions. High-intensity treadmill speeds were significantly faster than treadmill SSWS (standard practice; +227%; p < 0.0001) and overground SSWS (+142%; p = 0.003). 15 of the 21 subjects were able to walk on the treadmill at 150% of overground SSWS; with the remaining individuals (n = 6) walking at 123% of overground SSWS. Average peak heart rate during HIT was 90% of age-predicted max. CONCLUSIONS: These results demonstrate the feasibility of this single session HIT design and suggest that individuals following stroke are capable of prolonged training at speeds significantly faster than standard practice. Additionally, this training intensity elicited heart rate responses in the upper range of vigorous exercise. Future studies are needed to investigate a progressive HIT intervention applying this design and its effects on functional outcomes as well as cardiovascular fitness.

FES-assisted Cycling Improves Aerobic Capacity and Locomotor Function Postcerebrovascular Accident.

PURPOSE: After a cerebrovascular accident (CVA) aerobic deconditioning contributes to diminished physical function. Functional electrical stimulation (FES)-assisted cycling is a promising exercise paradigm designed to target both aerobic capacity and locomotor function. This pilot study aimed to evaluate the effects of an FES-assisted cycling intervention on aerobic capacity and locomotor function in individuals post-CVA. METHODS: Eleven individuals with chronic (>6 months) post-CVA hemiparesis completed an 8-wk (three times per week; 24 sessions) progressive FES-assisted cycling intervention. V˙O2peak, self-selected, and fastest comfortable walking speeds, gait, and pedaling symmetry, 6-min walk test (6MWT), balance, dynamic gait movements, and health status were measured at baseline and posttraining. RESULTS: Functional electrical stimulation-assisted cycling significantly improved V˙O2peak (12%, P = 0.006), self-selected walking speed (SSWS, 0.05 ± 0.1 m·s, P = 0.04), Activities-specific Balance Confidence scale score (12.75 ± 17.4, P = 0.04), Berg Balance Scale score (3.91 ± 4.2, P = 0.016), Dynamic Gait Index score (1.64 ± 1.4, P = 0.016), and Stroke Impact Scale participation/role domain score (12.74 ± 16.7, P = 0.027). Additionally, pedal symmetry, represented by the paretic limb contribution to pedaling (paretic pedaling ratio [PPR]) significantly improved (10.09% ± 9.0%, P = 0.016). Although step length symmetry (paretic step ratio [PSR]) did improve, these changes were not statistically significant (-0.05% ± 0.1%, P = 0.09). Exploratory correlations showed moderate association between change in SSWS and 6-min walk test (r = 0.74), and moderate/strong negative association between change in PPR and PSR. CONCLUSIONS: These results support FES-assisted cycling as a means to improve both aerobic capacity and locomotor function. Improvements in SSWS, balance, dynamic walking movements, and participation in familial and societal roles are important targets for rehabilitation of individuals after CVA. Interestingly, the correlation between PSR and PPR suggests that improvements in pedaling symmetry may translate to a more symmetric gait pattern.

Combining therapeutic approaches: rTMS and aerobic exercise in post-stroke depression: a case series.

Objective and importance Residual effects of stroke include well-documented functional limitations and high prevalence of depression. Repetitive transcranial magnetic stimulation (rTMS) and aerobic exercise (AEx) are established techniques that improve depressive symptoms, but a combination of the two has yet to be reported. The purpose of this case series is to examine the safety, feasibility, and impact of combined rTMS and AEx on post-stroke depression and functional mobility. Clinical presentation Three participants with a history of stroke and at least mild depressive symptoms (Patient Health Questionare-9 ≥5). Intervention Both rTMS and AEx were completed 3 times/week for 8-weeks. rTMS was applied to the left dorsolateral prefrontal cortex, 5000 pulses/session at 10 Hz, at an intensity of 120% of resting motor threshold. AEx consisted of 40 min of treadmill walking at 50-70% of heart rate reserve. Results Depressive symptoms improved in all three participants, with all demonstrating response (≥50% improvement in symptoms) and likely remission. All participants improved their Six Minute Walk Test distance and Participants 1 and 2 also improved Berg Balance Scale scores. Participants 1 and 3 improved overground walking speeds. No serious adverse events occurred with the application of rTMS or AEx and the participants' subjective reports indicated positive responses. Adherence rate for both rTMS and AEx was 98%. Conclusion Combined treatment of rTMS and AEx appears safe, feasible, and tolerable in individuals with a history of stroke and at least mild depressive symptoms. All participants had good compliance and demonstrated improvements in both depressive symptoms and walking capacity.

POWER training in chronic stroke individuals: differences between responders and nonresponders.

BACKGROUND: Lower extremity muscle weakness is a primary contributor to post-stroke dysfunction. Resistance training is an effective treatment for hemiparetic weakness and improves walking performance. Post-stroke subject characteristics that do or do not improve walking speed following resistance training are unknown. OBJECTIVE: The purpose of this paper was to describe baseline characteristics, as well as responses to training, associated with achieving a minimal clinically important difference (MCID) in walking speed (≥0.16 m/s) following Post-stroke Optimization of Walking Using Explosive Resistance (POWER) training. METHODS: Seventeen participants completed 24 sessions of POWER training, which included intensive progressive leg presses, jump training, calf raises, sit-to-stands, step-ups, and over ground fast walking. Outcomes included SSWS, FCWS, DGI, FMA-LE, 6-MWT, paretic knee power, non-paretic knee power, and paretic step ratio. RESULTS: Specific to those who reached MCID in SSWS (e.g. "responders"), significant improvements in SSWS, FCWS, 6-MWT, paretic knee power, and non-paretic knee power was realized. Paretic knee power and non-paretic knee power significantly improved in those who did not achieve MCID for gait speed (e.g. "non-responders"). CONCLUSION: The potential for POWER training to enhance general locomotor function was confirmed. Baseline paretic knee strength/power may be an important factor in how an individual responds to this style of training. The lack of change within the non-responders emphasizes the contribution of factors other than lower extremity muscle power improvement to locomotor dysfunction.

Continuous Ultrasound Decreases Pain Perception and Increases Pain Threshold in Damaged Skeletal Muscle.

OBJECTIVE: Determine whether therapeutic ultrasound (TUS) delivered in a continuous mode reduces pain perception after muscle injury. DESIGN: Randomized, double-blind trial. SETTING: Institutional laboratory. PARTICIPANTS: Twenty young healthy participants (11 females; 9 males; mean age ± SD, 24.1 ± 3.7 years). INTERVENTION: All subjects performed 50 maximal eccentric contractions of the biceps brachii on a Biodex dynamometer. Criterion measures of isometric force production and serum creatine kinase (CK) activity confirmed tissue damage. Both groups received either TUS or sham treatment everyday starting 24 hours after muscle damage. Muscle soreness and pain were assessed at baseline, 48 hours postdamage, and every other day for 8 days. MAIN OUTCOME MEASURES: Muscle pain was assessed with a battery of tests: visual analog scale (VAS), Short-form McGill Pain Questionnaire-2, joint angle changes, and mechanical pressure threshold. RESULTS: Confirmation of damage occurred with baseline compared to 48 hours after damage of isometric peak torque (N·m; P < 0.01) and CK activity (IU/I; P = 0.03). Our results showed significant treatment group differences in VAS (P = 0.01) and mechanical pressure threshold (P = 0.02) after the third TUS treatment in the distal bicep brachii region. CONCLUSIONS: Continuous TUS reduced pain perception and increased mechanical pressure threshold in the biceps brachii after muscle damage, specifically near the distal musculotendinous junction.

Physical Activity and the Risk of Depression in Community-Dwelling Korean Adults With a History of Stroke.

Background: Physical activity (PA) is believed to improve mental health, including depression. However, whether recommended PA levels have a similar impact in individuals with poststroke depression is unclear. Objective: The aim of this study was to apply a quasi-experimental propensity score (PS) matching control for covariate differences and compare the effects of PA on reducing depression risk among people with stroke. Design: A cross-sectional design was used for this study. Methods: Health-related information for community-dwelling adults (N=4,555) who reported having had a stroke was extracted from the 2013 Korean Community Health Survey data set. The survey participants were asked a series of questions about depression, recommended PA levels (moderate and vigorous intensity), and chronic conditions. A multivariable regression model, inverse probability weighting adjustment, and Greedy algorithms with 1:1 matching and covariate adjustment were used to estimate the effects of PA on risk of depression. The dependent variable was diagnosis of depression, and the primary independent variable was PA. Baseline covariates were 10 demographic and 9 chronic condition variables. Results: Without PS methods, there were significant differences in baseline covariates (16 out of 19) between people who performed PA and those who did not perform PA. After applying 1:1 matching, the number of patients in each group comparing the effect of PA numbered 1,970, and 13 covariates did not differ significantly between the 2 groups. Physical activity reduced the risk of poststroke depression by 36.1% to 42.4% (odds ratio=0.639-0.376) across the 3 methods. Limitations: Unaccounted-for covariates, including stroke severity, predepression status, and history of depression treatments, may have biased the results. Conclusions: The findings suggest that recommended PA levels have protective relationships with the risk of poststroke depression.

The Effects of POWER Training in Young and Older Adults after Stroke.

Background. Approximately 35,000 strokes occur annually in adults below the age of 40, and there is disappointingly little data describing their responses to rehabilitation. The purpose of this analysis was to determine the effects of Poststroke Optimization of Walking using Explosive Resistance (POWER) training in young (<40 years) and older (>60 years) adults and to describe relationships between training-induced improvements in muscular and locomotor function. Methods. Data was analyzed from 16 individuals with chronic stroke who participated in 24 sessions of POWER training. Outcomes included muscle power generation, self-selected walking speed (SSWS), 6-minute walk test, Fugl-Meyer motor assessment, Berg Balance Scale, and Dynamic Gait Index. Results. There were no significant differences between groups at baseline. Within-group comparisons revealed significant improvements in paretic and nonparetic knee extensor muscle power generation in both groups. Additionally, young participants significantly improved SSWS. Improvements in SSWS were more strongly associated with improvements in power generation on both sides in young versus older participants. Conclusions. Younger adults after stroke seem to preferentially benefit from POWER training, particularly when increasing gait speed is a rehabilitation goal. Future research should aim to further understand age-related differences in response to training to provide optimal treatments for all individuals following stroke.