Feasibility and preliminary efficacy of a theory-informed resistance exercise training single-arm intervention for major depression.

Many adults with major depressive disorder (MDD) do not receive effective treatment. The potential benefits of resistance exercise training (RET) are understudied and may be mechanistically related to cerebral blood flow changes. PURPOSE: To assess feasibility, acceptability, and preliminary efficacy of a 16-week, theory-informed RET trial for the treatment of MDD and explore changes in cerebral blood flow. METHODS: Ten adults with DSM-5-diagnosed MDD were enrolled in a single-arm, 16-week, twice-weekly, whole-body RET intervention, consistent with US and WHO Physical Activity resistance exercise guidelines. To build intrinsic motivation and develop exercise-preparatory habits, motivators and commitment were discussed weekly. Screening, enrollment, and intervention attendance and compliance rates documented feasibility. At baseline and weeks 8, 16, and 26, current MDD diagnosis, clinician-rated, and self-reported symptom severity were evaluated along with cerebral blood flow which was assessed as middle cerebral artery (MCA) mean blood velocity, conductance, and pulsatility. RESULTS: Nine participants completed the intervention. Strong feasibility and acceptability (98 % adherence, 93 % compliance, and 90 % retention) were found. MDD remission was reached by 8/9 participants at week 16 and persisted through week 26. There were large decreases in clinician-rated and self-reported symptoms at each assessment (Hedges' g = 0.84-2.13). There were small-to-moderate increases in MCA velocity (g = 0.32-0.57) and conductance (g = 0.20-0.76) across time, with minimal changes in pulsatility (all g < 0.21). CONCLUSIONS: Preliminary results suggest RET for MDD treatment is feasible and plausibly efficacious, finding large antidepressant effects. A sufficiently powered randomized controlled trial to assess RET's efficacy for treating MDD via potential cerebrovascular mechanisms is warranted.

Effects of aerobic exercise training on cerebral pulsatile hemodynamics in middle-aged adults with elevated blood pressure/stage 1 hypertension.

Mechanisms behind the protective effects of aerobic exercise on brain health remain elusive but may be vascular in origin and relate to cerebral pulsatility. This pilot study investigated the effects of 12-wk aerobic exercise training on cerebral pulsatility and its vascular contributors (large artery stiffness, characteristic impedance) in at-risk middle-aged adults. Twenty-eight inactive middle-aged adults with elevated blood pressure or stage 1 hypertension were assigned to either moderate/vigorous aerobic exercise training (AET) for 3 days/wk or no-exercise control (CON) group. Middle cerebral artery (MCA) pulsatility index (PI), large artery (i.e., aorta, carotid) stiffness, and characteristic impedance were assessed via Doppler and tonometry at baseline, 6, and 12 wk, whereas cardiorespiratory fitness (V̇o2peak) was assessed via incremental exercise test and cognitive function via computerized battery at baseline and 12 wk. V̇o2peak increased 6% in AET and decreased 4% in CON (P < 0.05). Proximal aortic compliance increased (P = 0.04, partial η2 = 0.14) and aortic characteristic impedance decreased (P = 0.02, partial η2 = 0.17) with AET but not CON. Cerebral pulsatility showed a medium-to-large effect size increase with AET, although not statistically significant (P = 0.07, partial η2 = 0.11) compared with CON. Working memory reaction time improved with AET but not CON (P = 0.02, partial η2 = 0.20). Our data suggest 12-wk AET elicited improvements in central vascular hemodynamics (e.g., proximal aortic compliance and characteristic impedance) along with apparent, paradoxical increases in cerebral pulsatile hemodynamics.NEW & NOTEWORTHY We identify differential central versus cerebrovascular responses to 12 wk of aerobic exercise training in middle-aged adults. Although proximal aortic compliance and characteristic impedance improved after 12 wk of exercise, cerebral pulsatility tended to unexpectedly increase. These data suggest short-term aerobic exercise training may lead to more immediate benefits in the central vasculature, whereas longer duration exercise training may be required for beneficial changes in pulsatility within the cerebrovasculature.

Law Enforcement Officers Have an Increased Prevalence of Subclinical Cardiovascular Disease That Is Not Explained by Traditional Risk Factors.

OBJECTIVES: The aim of the study is to determine if law enforcement officers develop subclinical atherosclerotic cardiovascular disease (ASCVD) earlier than nonofficers and, if so, the extent to which conventional risk factors explain this difference. Methods: Estimated pulse wave velocity (ePWV) was the marker of subclinical ASCVD. EPWV, ASCVD risk factors, metabolic syndrome (MetS), and 10-year risk for ASCVD were compared among 408 law enforcement officers and a civilian cohort. Results: EPWV, 10-year ASCVD risk, and MetS prevalence increased significantly with age. All but the officers age 55 and older had higher ePWV cohort than the civilian cohort ( P < 0.001). Ten-year ASCVD risk explained the most variability of ePWV ( R2 = 0.49, P < 0.001). Conclusions: Officers develop subclinical ASCVD earlier than nonofficers. Conventional ASCVD risk factors only explain about half of this increase. Occupational factors may play a role in contributing to this increased ASCVD risk.

Physical Activity Intensity and Risk of Dementia.

INTRODUCTION: Regular participation in aerobic physical activity is associated with a reduced risk of dementia. It is currently unclear whether this association is due to the total volume or intensity of physical activity. METHODS: This prospective cohort study analyzed 386,486 adults from the UK Biobank who were free of dementia and self-reported >0 minutes of moderate-to-vigorous intensity physical activity (MVPA) at baseline (2007-2010). Participants were categorized as performing 0%, >0%-30%, or >30% of their total MVPA in vigorous activity (VPA). Cox proportional hazards regression models were used to examine the associations between categories of VPA and incident dementia while adjusting for sociodemographic and lifestyle factors including total MVPA. Analyses were performed in 2022. RESULTS: Over an average follow-up of 12.0 (1.7) years, there were 5,177 (1.3%) cases of dementia. Compared to the group reporting 0% VPA, the hazard ratios (95% confidence intervals) of dementia for the groups reporting >0%-30% and >30% VPA were 0.73 (0.68-0.78) and 0.81 (0.75-0.87), respectively, in the fully adjusted model. In a joint analysis, reporting some VPA was associated with a reduced risk of dementia regardless of meeting the aerobic physical activity guidelines (HR=0.78 [0.72-0.85]) or not (HR=0.76 [0.60-0.98]), while meeting the aerobic physical activity guidelines alone without VPA was not associated with incident dementia (HR=0.98 [0.90-1.07]), compared to the group that did not meet the guidelines and reported no VPA. CONCLUSIONS: These results suggest that engaging in VPA as part of MVPA is associated with a lower risk of dementia.

Age-associated increases in middle cerebral artery pulsatility differ between men and women.

Mechanisms underlying sex differences in brain aging remain unclear but may relate to changes in cerebral pulsatile blood flow. Sex differences in the stiffening of the large arteries and expansion of pulse pressure with age may accelerate changes in pulsatile (i.e., discontinuous) blood flow in the brain that contribute to brain health. The purpose of this cross-sectional, secondary analysis was to examine sex differences in age-associated changes in large artery (aorta and carotid) stiffness, carotid pulse pressure, and cerebral pulsatility in 206 men and 217 women between 18 and 72 yr of age. Outcomes included aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)] and carotid pulse pressure via tonometry, carotid ß-stiffness via ultrasound, and middle cerebral artery (MCA) pulsatility index via transcranial Doppler. Regression analyses revealed a significant age-by-sex interaction, with women exhibiting a slower rate of change compared with men for cfPWV (ß = -0.21, P = 0.04), and greater rate of change for carotid stiffness (ß = 0.27, P = 0.02), carotid pulse pressure (ß = 0.98, P < 0.001), and MCA pulsatility index (ß = 0.49, P = 0.002) after adjustment for covariates. The significant age-by-sex interaction for MCA pulsatility was abolished after further adjustment for carotid pulse pressure. Women exhibit accelerated increases in cerebral pulsatility during midlife, likely driven by exaggerated increases in carotid stiffness and pulse pressure compared with men. These data suggest that there are disproportionate increases in cerebral pulsatility in women during midlife that could contribute to accelerated brain aging compared with men.NEW & NOTEWORTHY We identify sex-specific associations between increasing age and cerebral pulsatility and its vascular mechanisms. When compared with men, women in our cross-sectional analysis exhibited greater age-associated increases in carotid stiffness, carotid pulse pressure, and cerebral pulsatility particularly during midlife. These data suggest that the rapid expansion of pulse pressure during midlife contributes to an exaggerated increase in cerebral pulsatility among women and suggest a potential mechanism contributing to sex differences in brain aging.

Social isolation and subclinical vascular pathways to cerebrovascular disease.

Social isolation and lack of social support are risk factors for cardiovascular and cerebrovascular disease (CVD). This study explored the relationship between measures of social support and subclinical measures of CVD risk. 58 healthy adults ages 18 to 85 years participated in this study. The Berkman-Syme Social Network Inventory (SNI) was used to assess social isolation, with higher scores signifying less isolation. Social support was defined using the 12-Item Interpersonal Support Evaluation List (ISEL-12) with a higher score signifying higher social support. Subclinical CVD measures included carotid-femoral pulse wave velocity (cfPWV), carotid beta-stiffness index, and middle cerebral artery (MCA) pulsatility index. Path analysis models for both the SNI and ISEL appraisal domain predicting cfPWV and cerebrovascular pulsatility fit the data well. Path analyses showed significant direct paths from the SNI (ß = -.363, t = -2.91) and ISEL appraisal domain (ß = -.264, t = -2.05) to cfPWV. From cfPWV, both models revealed significant direct paths to carotid stiffness (ß = .488, t = 4.18) to carotid pulse pressure (ß = .311, t = 2.45) to MCA pulsatility (ß = .527, t = 4.64). Social isolation and appraisal of social support are related to unfavorably higher aortic stiffness, with subsequent detrimental effects on cerebrovascular hemodynamic pulsatility.

Point/counterpoint: Arterial blood pressure response to exercise does not relate to exercise-induced improvement in cognitive function.

Acute exercise has been shown to transiently improve specific aspects of cognitive function, however the mechanism governing these effects remain unclear. Blood pressure responses during exercise have been hypothesized to be a primary contributing factor, in part through its influence on cerebral blood flow. In this counterpoint, we highlight the inconsistent and weak associations between changes in blood pressure, cerebral blood flow and cognitive responses during and following acute exercise. Despite sound theoretical foundation, cognitive responses to exercise do not appear strongly related to blood pressure and more likely stem from a complex integration of multiple mechanisms.

Estimated pulse wave velocity as a measure of vascular aging.

BACKGROUND: Carotid-femoral pulse wave velocity (cfPWV), the referent measure of aortic stiffness, is an established measure of vascular aging. In studies where cfPWV cannot be measured, alternative methods are needed to help promote research on vascular aging. This study examines the construct validity of a measure of PWV estimated from age and blood pressure (ePWV). The specific aims of the study are to: 1) explore the strength of association between ePWV, cfPWV, and other established measures of vascular aging; 2) examine the sensitivity and specificity of elevated ePWV (≥10m/s) in relation to elevated cfPWV (≥10m/s). METHODS: We measured cfPWV in two-hundred and fifty-two adults (mean age 57±12 years, 48% female) and calculated each participant's ePWV from their age and brachial blood pressure. Additional measures of vascular aging included: carotid intima-media thickness (cIMT); carotid stiffness measured as elastic modulus (cEp); and carotid augmentation index (cAIx). RESULTS: The correlations between cfPWV and measures of vascular aging were: cEp (r = 0.36), cIMT (r = 0.49), and cAIx (r = 0.04). The correlations between ePWV and measures of vascular aging were: cEp (r = 0.45), cIMT (r = 0.60), and cAIx (r = 0.24). The correlation between ePWV and cfPWV was (r = 0.67). The sensitivity and specificity of elevated ePWV (≥ 10 m/s) for concomitantly identifying high cfPWV (≥ 10 m/s) were 85.4% and 73.0% respectively. CONCLUSION: ePWV is associated with established measures of vascular aging, such as carotid thickness, carotid stiffness and carotid augmentation index. ePWV may be a useful tool to help promote research on vascular aging.

Influence of sex and presence of cardiovascular risk factors on relations between cardiorespiratory fitness and cerebrovascular hemodynamics.

Cerebral hemodynamics and pulsatility are important mechanisms of cerebrovascular and brain health. Cardiorespiratory fitness may improve cerebrovascular pulsatility in healthy females, but not in males. Whether cardiovascular disease (CVD) risk factors modify sex-specific associations of fitness with cerebral hemodynamics and vascular contributors to cerebral hemodynamics is unknown. We assessed V̇o2peak and cerebrovascular hemodynamics in 157 adults without (42 ± 13 yr, BMI 24.5 ± 2.7 kg/m2), and 66 adults with modifiable CVD risk factors (54 ± 8 yr, BMI 29.9 ± 4.0 kg/m2). Intracranial [middle cerebral artery (MCA) pulsatility index (PI), mean velocity, conductance, and pulsatile damping] and extracranial hemodynamics [carotid artery wave transmission/reflection, PI, pulse wave velocity (PWV)-ß, and carotid-femoral PWV] were assessed via transcranial Doppler/ultrasound and tonometry. Cardiorespiratory fitness was assessed via V̇o2peak during an incremental exercise test. Multiple regression was used to assess contributions of V̇o2peak to cerebrovascular outcomes after adjustment for relevant covariates. V̇o2peak was inversely associated with MCA PI among females (ß = -0.39, P = 0.01) but not males (ß = -0.16, P = 0.25) without CVD risk factors. V̇o2peak was positively associated with MCA PI among females (ß = 0.44, P = 0.01) and not associated in males with CVD risk factors (ß = -0.06, P = 0.079). V̇o2peak was beneficially associated with vascular contributors to cerebral hemodynamics but had sex-specific associations with carotid stiffness and pulse pressure in females without CVD risk factors only. These results suggest that sex-specific associations between fitness and cerebral pulsatility among females without CVD risk factors may relate to the differential effects of fitness on carotid stiffness and pulse pressure. In addition, the presence of modifiable CVD risk factors may influence the protective relations of fitness on cerebrovascular hemodynamics.NEW & NOTEWORTHY We identify beneficial associations between cardiorespiratory fitness and lower carotid stiffness and pulse pressure as potential mechanisms underlying sex-specific associations of fitness and cerebral pulsatility in females without modifiable risk factors. Greater fitness is beneficially associated with conductance, pulsatile damping, and forward wave energy among adults without risk factors; however, associations are attenuated among adults with modifiable risk factors. These data suggest sex and risk factors may alter cerebrovascular sensitivity to cardiorespiratory fitness.

Exercise as an Aging Mimetic: A New Perspective on the Mechanisms Behind Exercise as Preventive Medicine Against Age-Related Chronic Disease.

Age-related chronic diseases are among the most common causes of mortality and account for a majority of global disease burden. Preventative lifestyle behaviors, such as regular exercise, play a critical role in attenuating chronic disease burden. However, the exact mechanism behind exercise as a form of preventative medicine remains poorly defined. Interestingly, many of the physiological responses to exercise are comparable to aging. This paper explores an overarching hypothesis that exercise protects against aging/age-related chronic disease because the physiological stress of exercise mimics aging. Acute exercise transiently disrupts cardiovascular, musculoskeletal, and brain function and triggers a substantial inflammatory response in a manner that mimics aging/age-related chronic disease. Data indicate that select acute exercise responses may be similar in magnitude to changes seen with +10-50 years of aging. The initial insult of the age-mimicking effects of exercise induces beneficial adaptations that serve to attenuate disruption to successive "aging" stimuli (i.e., exercise). Ultimately, these exercise-induced adaptations reduce the subsequent physiological stress incurred from aging and protect against age-related chronic disease. To further examine this hypothesis, future work should more intricately describe the physiological signature of different types/intensities of acute exercise in order to better predict the subsequent adaptation and chronic disease prevention with exercise training in healthy and at-risk populations.

Exploration of cerebral hemodynamic pathways through which large artery function affects neurovascular coupling in young women.

Background: The interactions between large artery function and neurovascular coupling (NVC) are emerging as important contributors to cognitive health. Women are disproportionally affected by Alzheimer's disease and related dementia later in life. Understanding large artery correlates of NVC in young women may help with preservation of cognitive health with advancing age. Purpose: To explore the association between large artery function, NVC and cognitive performance in young women. Methods: Vascular measurements were made in 61 women (21 ± 4 yrs) at rest and during a cognitive challenge (Stroop task). Transcranial Doppler was used to measure left middle cerebral artery (MCA) maximum velocity (Vmax), mean velocity (Vmean), and pulsatility index (PI). NVC was determined as MCA blood velocity reactivity to the Stroop task. Large artery function was determined using carotid-femoral pulse wave velocity (cfPWV) as a proxy measure of aortic stiffness and carotid ultrasound-derived measures of compliance and reactivity (diameter change to the Stroop task). Cognitive function was assessed separately using a computerized neurocognitive battery that included appraisal of response speed, executive function, information processing efficiency, memory, attention/concentration, and impulsivity. Results: MCA Vmax reactivity was positively associated with executive function (ß = 0.26, 95% CI 0.01-0.10); MCA Vmean reactivity was negatively associated with response speed (ß = -0.33, 95% CI -0.19 to -0.02) and positively with memory score (ß = 0.28, 95% CI 0.01-0.19). MCA PI reactivity was negatively associated with attention performance (ß = -0.29, 95% CI -14.9 to -1.0). Path analyses identified significant paths (p < 0.05) between carotid compliance and carotid diameter reactivity to select domains of cognitive function through MCA reactivity. Conclusions: NVC was associated with cognitive function in young women. Carotid artery function assessed as carotid compliance and carotid reactivity may contribute to optimal NVC in young women through increased blood flow delivery and reduced blood flow pulsatility.

The effect of aging on carotid artery wall mechanics during maximal resistance exercise.

INTRODUCTION: Age-related stiffening of the large elastic arteries (e.g., common carotid artery [CCA]) may impair wall dynamics (i.e., strain) and amplify transmission of pulsatile blood flow into the brain with large increases in pressure that occur during maximal resistance exercise (RE). The purpose of this study was to compare CCA arterial wall dynamics, central hemodynamics, and cerebral blood velocity responses during maximal RE between young and older adults. METHODS: Thirty-one young (YA; 26 ± 5 yrs; 23.8 ± 3.3 kg/m2) and 25 older adults (OA; 60 ± 6 yrs; 30.0 ± 5.5 kg/m2) performed a unilateral maximal isokinetic knee flexion/extension exercise protocol (i.e., maximal RE). All measures were recorded at baseline and during the last 10 s of maximal RE. Common carotid artery strain, CCA strain time to peak, and CCA strain rate (i.e., variables of arterial wall dynamics) were analyzed using 2D speckle tracking software from circumferential ultrasound images. Transcranial Doppler was used to measure right middle cerebral artery (MCA) blood velocity. Non-invasive arterial blood pressure measurements were obtained using finger photoplethysmography. RESULTS: Older adults had greater reductions in CCA strain time to peak from baseline to maximal RE (345 ± 39 to 242 ± 52 ms) than YA (308 ± 35 to 247 ± 42 ms; interaction effect, p < 0.01). MCA velocity was similar between YA and OA during maximal RE (p = 0.48), despite a greater arterial pressor response in OA (p < 0.01). CONCLUSION: These data suggest cerebral blood velocity responds similarly during maximal RE among OA compared to YA, despite subtle age-related differences in the pressor and extracranial vascular response during maximal RE.

Physical activity is associated with lower pulsatile stress but not carotid stiffness in children.

The cardiovascular disease (CVD) process may begin early in life when accompanied by atherosclerotic risk factors. CVD risk factors in children are associated with stiffening of the large elastic arteries, a reflection of subclinical atherosclerosis. Physical activity is a preventative lifestyle strategy that may benefit arterial stiffness by attenuating the hemodynamic stress on the artery wall. This study examined the relations between physical activity, carotid pulsatile stress, and carotid stiffness in children. One hundred and forty children (9-11 yrs; 50.0% male, 57.9% African-American, 42.10% Caucasian, body mass index (BMI) 20.1 ± 4.7 kg/m2) participated in this study. Physical activity counts were measured using a wrist-worn accelerometer and averaged over 7 days. Carotid artery ß-stiffness and pulse pressure (calibrated to brachial mean and diastolic pressure) were assessed as via ultrasound and tonometry, respectively. Pulsatile stress was calculated as the product of carotid pulse pressure and heart rate. Physical activity counts were correlated with pulsatile stress (r = -0.27), and BMI (r = -0.23), but were unrelated to carotid stiffness. In multivariate models, associations between physical activity counts and pulsatile stress remained (B = -1.3 [95%CI, -2.4, -0.2], ß = -0.20, p < 0.05) after covariate adjustment for age, race, sex, pubertal stage, and BMI. Carotid pulsatile stress was related to regional carotid stiffness (r = 0.45, p < 0.05). These data suggest that higher levels of physical activity at young age are associated with lower hemodynamic stress in the carotid artery. Findings are discussed in the context of an inverse relationship between hemodynamic pulsatile stress and carotid stiffness in children.

Oral vitamin C restores endothelial function during acute inflammation in young and older adults.

Oxidative stress has been linked to reductions in vascular function during acute inflammation in young adults; however, the effect of acute inflammation on vascular function with aging is inconclusive. The aim of this study was to determine if oral antioxidant administration eliminates vascular dysfunction during acute inflammation in young and older adults. Brachial flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (PWV) were measured in nine young (3 male, 24 ± 4 yrs, 26.2 ± 4.9 kg/m2 ) and 16 older (13 male, 64 ± 5 yrs, 25.8 ± 3.2 kg/m2 ) adults before and 2-h after oral consumption of 2 g of vitamin C. The vitamin C protocol was completed at rest and 24 h after acute inflammation was induced via the typhoid vaccine. Venous blood samples were taken to measure markers of inflammation and vitamin C. Both interleukin-6 (Δ+0.7 ± 1.8 pg/ml) and C-reactive protein (Δ+1.9 ± 3.1 mg/L) were increased at 24 h following the vaccine (p < 0.01). There was no change in FMD or PWV following vitamin C administration at rest (p > 0.05). FMD was lower in all groups during acute inflammation (Δ-1.4 ± 1.9%, p < 0.01), with no changes in PWV (Δ-0.0 ± 0.9 m/s, p > 0.05). Vitamin C restored FMD back to initial values in young and older adults during acute inflammation (Δ+1.0 ± 1.8%, p < 0.01) with no change in inflammatory markers or PWV (p > 0.05). In conclusion, oral vitamin C restored endothelial function during acute inflammation in young and older adults, with no effect on aortic stiffness. The effect of vitamin C on endothelial function did not appear to be due to reductions in inflammatory markers. The exact mechanisms should be further investigated.

Assessment of Cerebrovascular Dynamics and Cognitive Function with Acute Aerobic Exercise in Persons with Multiple Sclerosis.

BACKGROUND: Cognitive dysfunction in multiple sclerosis (MS) may partially stem from inadequate cerebral blood flow. Cerebral blood flow and cognitive function improve with aerobic exercise in healthy adults. The effect of aerobic exercise on cerebrovascular hemodynamics and cognitive performance in persons with MS is unclear. The acute effect of aerobic exercise versus quiet rest on cerebrovascular hemodynamics and cognitive performance in relapsing-remitting MS was examined. METHODS: Sixteen adults with relapsing-remitting MS underwent cerebrovascular hemodynamics and cognitive performance testing before, 2 minutes after, and 30 minutes after aerobic exercise (20-minute treadmill walking, 60% peak oxygen consumption) and a time-matched seated control. Brachial blood pressure was obtained via an oscillometric cuff. Right middle cerebral artery (MCA) blood velocity was measured via transcranial Doppler and used to calculate mean velocity, pulsatility index (PI), and conductance. Carotid artery stiffness was measured via ultrasonography and tonometry. Cognitive performance (accuracy, reaction time) was assessed using a modified flanker task. RESULTS: Exercise elicited significant increases in mean pressure and carotid artery stiffness and decreases in MCA conductance at 2 minutes after exercise, which subsided by 30 minutes (P < .05). Exercise did not significantly alter MCA PI. Flanker reaction time decreased during posttesting in both conditions (P < .05). There were no condition × time interactions for cognitive performance. CONCLUSIONS: Persons with MS seem resilient to exercise-induced acute changes in MCA PI despite transient carotid stiffening, potentially via reductions in MCA conductance. These data suggest that changes in cognitive performance after acute aerobic exercise are not directly related to transient cerebrovascular responses in persons with MS.

Problem-solving therapy-induced amygdala engagement mediates lifestyle behavior change in obesity with comorbid depression: a randomized proof-of-mechanism trial.

BACKGROUND: Depression hinders obesity treatment; elucidating mechanisms may enable treatment enhancements. OBJECTIVES: The aim was to investigate whether changes in neural targets in the negative affect circuit following psychotherapy mediate subsequent changes in weight and behaviors. METHODS: Adults (n = 108) with obesity and depression were randomly assigned to usual care or an intervention that delivered problem-solving therapy (PST) for depression over 2 mo. fMRI for brain imaging was performed at baseline and 2 mo. BMI, physical activity, and diet were measured at baseline and 12 mo. Mediation analysis assessed between-group differences in neural target changes using t test and correlations between neural target changes and outcome changes (simple and interaction effect) using ordinary least-squares regression. RESULTS: Compared with usual care, PST led to reductions in left amygdala activation (-0.75; 95% CI: -1.49, -0.01) and global scores of the negative affect circuit (-0.43; -0.81, -0.06), engaged by threat stimuli. Increases in amygdala activation and global circuit scores at 2 mo correlated with decreases in physical activity outcomes at 12 mo in the usual-care group; these relations were altered by PST. In relation to change in leisure-time physical activity, standardized ß-coefficients were -0.67 in usual care and -0.01 in the intervention (between-group difference: 0.66; 0.02, 1.30) for change in left amygdala activation and -2.02 in usual care and -0.11 in the intervention (difference: 1.92; 0.64, 3.20) for change in global circuit scores. In relation to change in total energy expenditure, standardized ß-coefficients were -0.65 in usual care and 0.08 in the intervention (difference: 0.73; 0.29, 1.16) for change in left amygdala activation and -1.65 in usual care and 0.08 in the intervention (difference: 1.74; 0.85, 2.63) for change in global circuit scores. Results were null for BMI and diet. CONCLUSIONS: Short-term changes in the negative affect circuit engaged by threat stimuli following PST for depression mediated longer-term changes in physical activity. This trial was registered at www.clinicaltrials.gov as NCT02246413 (https://clinicaltrials.gov/ct2/show/NCT02246413).

Sex differences in cardiovascular adaptations in recreational marathon runners.

INTRODUCTION: There are well-established sex differences in central hemodynamic and cardiac adaptations to endurance exercise; however, controversial evidence suggests that excessive endurance exercise may be related to detrimental cardiovascular adaptations in marathoners. PURPOSE: To examine left ventricle (LV) structure, LV function, 24-h central hemodynamics and ventricular-vascular coupling in male and female marathoners and recreationally active adults. METHODS: 52 marathoners (41 ± 5 years, n = 28 female, completed 6 ± 1 marathons/3 years) and 49 recreationally active controls (42 ± 5 years, n = 25 female) participated in the study. Three-Dimensional Echocardiography (3DE) was used to measure LV mass index and LV longitudinal (LS) circumferential (CS), area (AS), and radial strain (RS). An ambulatory blood pressure (BP) cuff was used to measure 24-h central hemodynamics (BP, pulse wave velocity, PWV, wave reflection index, RIx). Hemodynamic and 3DE measures were combined to derive the ratio of arterial elastance (Ea) to ventricular elastance (Elv) as a global measure of ventricular-vascular coupling. RESULTS: There were no sex or group differences in LS, CS, AS, and RS (p > 0.05). Females marathoners had similar aortic BP (116 ± 9 vs. 113 ± 1 mmHg), and PWV (5.9 ± 0.5 vs. 5.9 ± 1.1 m/s) compared to female controls but lower aSBP (116 ± 9 vs. 131 ± 10 mmHg) and PWV (5.9 ± 0.5 vs. 6.2 ± 0.5 m/s) compared to male marathoners (p < 0.05). Female marathoners had lower Ea/Elv than female controls (0.67 ± 0.20 vs. 0.93 ± 0.36) and male marathoners (0.67 ± 0.20 vs. 0.85 ± 0.42, p < 0.05). CONCLUSIONS: Women that have completed multiple marathons do not have reduced LV function or increased aortic stiffness and may have better ventricular-vascular coupling compared to male marathoners and their female untrained counterparts.

Impact of acute changes in blood pressure and arterial stiffness on cerebral pulsatile haemodynamics in young and middle-aged adults.

NEW FINDINGS: What is the central question of this study? Does cerebrovascular pulsatility respond differently to acute increases in arterial stiffness in middle-aged compared with young adults? What is the main finding and its importance? Compared with young adults, middle-aged adults exhibited similar changes in cerebral pulsatile damping despite attenuated changes in carotid diameter and cerebrovascular pulsatility during blood pressure-dependent, but not blood pressure-independent, increases in large artery stiffness. ABSTRACT: Acute manipulation of arterial stiffness through interventions that increase sympathetic activity might provoke cerebral pulsatility and damping and reveal whether cerebrovascular haemodynamics respond differently to transient elevations in arterial stiffness in middle-aged compared with young adults. We compared cerebral pulsatility and damping in middle-aged versus young adults during two different sympathetic interventions [cold pressor test (CP) and lower-body negative pressure (LBNP)] that increase arterial stiffness acutely. Cerebrovascular haemodynamics were assessed in 15 middle-aged (54 ± 7 years old; 11 female) and 15 sex-matched young adults (25 ± 4 years old) at rest and during the CP test (4 min, 6.4 ± 0.8°C) and LBNP (6 min, -20 mmHg). Mean blood pressure was measured continuously via finger photoplethysmography. Carotid-femoral pulse wave velocity (cfPWV) and carotid stiffness were measured via tonometry and ultrasound. Blood velocity pulsatility index (PI) was measured at the middle cerebral (MCA) and common carotid artery (CCA) using Doppler, with pulsatile damping calculated as CCA PI divided by MCA PI. Increases in cfPWV were driven by changes in mean pressure during CP but not during LBNP in both groups (P < 0.05). Pulsatile damping decreased in both groups (P < 0.05) despite reductions in MCA PI and greater carotid dilatation during CP in young compared with middle-aged adults (P < 0.05). Pressure-independent increases in cfPWV during LBNP did not alter pulsatile damping but decreased MCA PI in both young and middle-aged adults (P < 0.05). These data suggest that changes in carotid diameter and cerebrovascular pulsatility differ between young and middle-aged adults despite similar changes in cerebral pulsatile damping during blood pressure-dependent, but not blood pressure-independent, increases in large artery stiffness.