Cj Marley

Elevated Aerobic Fitness Sustained Throughout the Adult Lifespan Is Associated With Improved Cerebral Hemodynamics

Background and Purpose— Age-related impairments in cerebral blood flow and cerebrovascular reactivity to carbon dioxide (CVRCO2) are established risk factors for stroke that respond favorably to aerobic training. The present study examined to what extent cerebral hemodynamics are improved when training is sustained throughout the adult lifespan. Methods— Eighty-one healthy males were prospectively assigned to 1 of 4 groups based on their age (young, ⩽30 years versus old, ≥60 years) and lifetime physical activity levels (trained, ≥150 minutes recreational aerobic activity/week versus sedentary, no activity). Middle cerebral artery blood velocity (MCAv, transcranial Doppler ultrasound), mean arterial pressure (MAP, finger photoplethysmography), and end-tidal partial pressure of carbon dioxide (PETCO2, capnography) were recorded during normocapnia and 3 mins of iso-oxic hypercapnea (5% CO2). Cerebrovascular resistance/conductance indices (CVRi/CVCi) were calculated as MAP/MCAv and MCAv/MAP, respectively, and CVRCO2 as the percentage increase in MCAv from baseline per millimeter of mercury (mm Hg) increase in PETCO2. Maximal oxygen consumption ( O2MAX, online respiratory gas analysis) was determined during cycling ergometry. Results— By design, older participants were active for longer (49±5 versus 6±4 years, P<0.05). Physical activity attenuated the age-related declines in O2MAX, MCAv, CVCi, and CVRCO2 and increase in CVRi (P<0.05 versus sedentary). Linear relationships were observed between O2MAX and both MCAv and CVRCO2 (r=0.58–0.77, P<0.05). Conclusions— These findings highlight the importance of maintaining aerobic fitness throughout the lifespan given its capacity to improve cerebral hemodynamics in later-life.

Impaired cerebral haemodynamic function associated with chronic traumatic brain injury in professional boxers

The present study examined to what extent professional boxing compromises cerebral haemodynamic function and its association with CTBI (chronic traumatic brain injury). A total of 12 male professional boxers were compared with 12 age-, gender- and physical fitness-matched non-boxing controls. We assessed dCA (dynamic cerebral autoregulation; thigh-cuff technique and transfer function analysis), CVRCO₂ (cerebrovascular reactivity to changes in CO₂: 5% CO₂ and controlled hyperventilation), orthostatic tolerance (supine to standing) and neurocognitive function (psychometric tests). Blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasound), mean arterial blood pressure (finger photoplethysmography), end-tidal CO₂ (capnography) and cortical oxyhaemoglobin concentration (near-IR spectroscopy) were continuously measured. Boxers were characterized by fronto-temporal neurocognitive dysfunction and impaired dCA as indicated by a lower rate of regulation and autoregulatory index (P<0.05 compared with controls). Likewise, CVRCO₂ was also reduced resulting in a lower CVRCO₂ range (P<0.05 compared with controls). The latter was most marked in boxers with the highest CTBI scores and correlated against the volume and intensity of sparring during training (r=-0.84, P<0.05). These impairments coincided with more marked orthostatic hypotension, cerebral hypoperfusion and corresponding cortical de-oxygenation during orthostatic stress (P<0.05 compared with controls). In conclusion, these findings provide the first comprehensive evidence for chronically impaired cerebral haemodynamic function in active boxers due to the mechanical trauma incurred by repetitive, sub-concussive head impact incurred during sparring training. This may help explain why CTBI is a progressive disease that manifests beyond the active boxing career.

Acute exercise stress reveals cerebrovascular benefits associated with moderate gains in cardiorespiratory fitness

Elevated cardiorespiratory fitness improves resting cerebral perfusion, although to what extent this is further amplified during acute exposure to exercise stress and the corresponding implications for cerebral oxygenation remain unknown. To examine this, we recruited 12 moderately active and 12 sedentary healthy males. Middle cerebral artery blood velocity (MCAv) and prefrontal cortical oxyhemoglobin (cO2Hb) concentration were monitored continuously at rest and throughout an incremental cycling test to exhaustion. Despite a subtle elevation in the maximal oxygen uptake (active: 52 ± 9 ml/kg per minute versus sedentary: 33 ± 5 ml/kg per minute, P < 0.05), resting MCAv was not different between groups. However, more marked increases in both MCAv (+28 ± 13% versus +18 ± 6%, P < 0.05) and cO2Hb (+5 ±4% versus −2 ± 3%, P < 0.05) were observed in the active group during the transition from low- to moderate-intensity exercise. Collectively, these findings indicate that the long-term benefits associated with moderate increase in physical activity are not observed in the resting state and only become apparent when the cerebrovasculature is challenged by acute exertional stress. This has important clinical implications when assessing the true extent of cerebrovascular adaptation.

Brain train to combat brain drain; focus on exercise strategies that optimise neuroprotection

What is the topic of this review? The topic of this review is to consider innovative exercise strategies that optimize neuroprotection in order to combat cognitive decline and neurodegenerative disease in older age. What advances does it highlight? The review summarizes current understanding around exercise mode, duration, frequency and intensity, and then highlights adaptive roles of select stressors that have equal if not indeed greater capacity than exercise per se to induce health‐related adaptation in the brain. These stressors include, but are not exclusively limited to, hydrostatic and thermal stress, hypoxia, nutritional supplementation and cognitive loading, and are effective by targeting specific pathways that collectively contribute towards improved brain structure and function.

Effects of exercise intensity on clot microstructure and mechanical properties in healthy individuals

BACKGROUND Exercise is well established to lead to exercise-induced hypercoagulability, as demonstrated by kinetic coagulation markers. It remains unclear as to whether exercise-induces changes lead in clot development and increased polymerisation. Fractal dimension (df) has been shown to act as a marker of clot microstructure and mechanical properties, and may provide a more meaningful method of determining the relationship between exercise-induced hypercoagulability and potential clot development. METHODS df was measured in 24 healthy individuals prior to, after 5min of submaximal exercise, following maximal exercise, 45min of passive recovery and following 60min of recovery. Results were compared with conventional markers of coagulation, fibrinolysis and SEM images. RESULTS Significantly increased df was observed following exercise, returning to resting values following 60min of recovery. The relationship between df and mature clot microstructure was confirmed by SEM: higher df was associated with dense clots formed of smaller fibrin fibres immediately following exercise compared to at rest. Conventional markers of coagulation confirmed findings of previous studies. CONCLUSION This study demonstrates that df is a sensitive technique which quantifies the structure and properties of blood clots following exercise. In healthy individuals, the haemostatic balance between coagulation and fibrinolysis is maintained in equilibrium following exercise. In individuals with underlying vascular damage who participate in exercise, this equilibrium may be displaced and lead to enhanced clot formation and a prothrombotic state. df may therefore have the potential to not only quantify hypercoagulability, but may also be useful in screening these individuals.

Redox‐regulation of haemostasis in hypoxic exercising humans: a randomised double‐blind placebo‐controlled antioxidant study

In vitro evidence has identified that coagulation is activated by increased oxidative stress, though the link and underlying mechanism in humans have yet to be established. We conducted the first randomised controlled trial in healthy participants to examine if oral antioxidant prophylaxis alters the haemostatic responses to hypoxia and exercise given their synergistic capacity to promote free radical formation. Systemic free radical formation was shown to increase during hypoxia and was further compounded by exercise, responses that were attenuated by antioxidant prophylaxis. In contrast, antioxidant prophylaxis increased thrombin generation at rest in normoxia, and this was normalised only in the face of prevailing oxidation. Collectively, these findings suggest that human free radical formation is an adaptive phenomenon that serves to maintain vascular haemostasis.

Post-prandial hyperlipidaemia results in systemic nitrosative stress and impaired cerebrovascular function in the aged

Post-prandial hyperlipidaemia (PPH) acutely impairs systemic vascular endothelial function, potentially attributable to a free radical-mediated reduction in vascular nitric oxide (NO) bioavailability (oxidative-nitrosative stress). However, it remains to be determined whether this extends to the cerebrovasculature. To examine this, 38 (19 young (≤35 years) and 19 aged (≥60 years)) healthy males were recruited. Cerebrovascular function (middle cerebral artery velocity, MCAv) and cerebrovascular reactivity to hypercapnea (CVRCO2Hyper) and hypocapnea (CVRCO2Hypo) were determined via trans-cranial Doppler ultrasound and capnography. Venous blood samples were obtained for the assessment of triglycerides (photometry), glucose (photometry), insulin (radioimmunoassay), ascorbate free radical (A•-, electron paramagnetic resonance spectroscopy) and nitrite (NO2-, ozone-based chemiluminescence) in the fasted state prior to and 4 h following consumption of a standardized high-fat meal (1362 kcal; 130 g of fat). Circulating triglycerides, glucose and insulin increased in both groups following the high-fat meal (P<0.05), with triglycerides increasing by 1.37 ± 1.09 mmol/l in the young and 1.54 ± 1.00 mmol/l in the aged (P<0.05). This resulted in an increased systemic formation of free radicals in the young (P<0.05) but not the aged (P>0.05) and corresponding reduction in NO2- in both groups (P<0.05). While the meal had no effect on MCAv in either age group, CVRCO2Hyper was selectively impaired in the aged (P<0.05). These findings indicate that PPH causes acute cerebrovascular dysfunction in the aged subsequent to systemic nitrosative stress.

Antioxidant intake among maladapted highlanders: link to vascular function

Exposure to high altitude leads to an increased formation of free radicals. This, in Chronic Mountain Sickness sufferers (CMS+), may contribute to systemic vascular dysfunction in comparison to the well-adapted controls (CMS-). The protective role of dietary antioxidants in minimising oxidative stress has been well documented. Furthermore, the nutritional shift from locally sourced foods to westernised, nutrients depleted diet in Latin American urban areas, is also reported. The aim of the study was to investigate vascular function and intake of dietary antioxidants in healthy, well-adapted and diseased maladapted highlanders born and bred in La Paz, Bolivia. We hypothesised that CMS sufferers will show impaired vascular function and low intake of dietary antioxidants compared to well-adapted highlander residents. To address the aims, 2 studies were completed. Study 1: twenty-five male highlanders participated in the study; 13 of which were CMS+ [mean age 57 (SD 7) years] and 12 were CMS[mean age 52 (SD 9) years]. Vascular function was assessed using pulse wave analysis and flow-mediated dilation (FMD). Pulse wave analysis was used to derive a normalized augmentation index (AIx) from the radial artery using the SphygmoCor system (AtCor Medical Pty Ltd), while FMD was assessed according to international guidelines using a high-resolution ultrasound machine (Acuson P50, Siemens) and expressed as a percentage change of the brachial artery from baseline (Studio; Computer Vision Group). Study 2: thirty-six male highlanders; 22 of which were CMS+ [mean age 52 (SD 9) years] and 14 were CMS[mean age 52 (SD 12) years] were interviewed to collect a 24-hour structured dietary recall using a portion size photo atlas. The stages followed in the UK Low Income Diet and Nutrition survey were used. Dietary data were analysed using NetWISP dietary analysis software (Version 4.0, Tinuviel Software; Anglesey, UK). Distribution of normality was determined using Shapiro-W-Wilks tests. Vascular data were analysed using independent samples t-tests and dietary data were analysed using Kruskal-Wallis and Mann-Whitney tests. Significance level was established at P < 0·05 and data are expressed as mean and standard deviation (SD). Study 1: FMD was lower and AIx was higher in CMS+ compared to CMS(P< 0·05; table). Study 2: Consumption of vitamin C and carotene were lower in the CMS+ in comparison to CMSshowing borderline significant

Failure to account for practice effects leads to clinical misinterpretation of cognitive outcome following carotid endarterectomy

Carotid endarterectomy (CEA) is a surgical procedure to remove stenotic atherosclerotic plaque from the origin of the carotid artery to reduce the risk of major stroke. Its impact on postoperative cognitive function (POCF) remains controversial; complicated, in part, by a traditional failure to account for practice effects incurred during consecutive psychometric testing. To address this for the first time, we performed psychometric testing (learning and memory, working memory, attention and information processing, and visuomotor coordination) in 15 male patients aged 68 ± 8 years with symptomatic carotid stenosis the day before and 24 h following elective CEA (two consecutive tests, 48 h apart). Multiple baselining was also performed in a separate cohort of 13 educationally, anthropometrically and age‐matched controls (63 ± 9 years) not undergoing revascularization at identical time points with additional measures performed over a further 96 h (four consecutive tests, each 48 h apart). A single consecutive test in the control group resulted in progressive improvements in learning and memory, working memory, and attention and information (P < 0.05 vs. Test 1), with three tests required before cognitive performance stabilized. Following correction for practice effects in the patient group, CEA was associated with a deterioration rather than an improvement in learning and memory as originally observed (P < 0.05). These findings highlight the potential for the clinical misinterpretation of POCF unless practice effects are taken into account and provide practical recommendations for implementation within the clinical setting.