A prospective cohort study about the effect of repeated living high and working higher on cerebral autoregulation in unacclimatized lowlanders

Cerebral autoregulation (CA) is impaired during acute high-altitude (HA) exposure, however, effects of temporarily living high and working higher on CA require further investigation. In 18 healthy lowlanders (11 women), we hypothesized that the cerebral autoregulation index (ARI) assessed by the percentage change in middle cerebral artery peak blood velocity (Δ%MCAv)/percentage change in mean arterial blood pressure (Δ%MAP) induced by a sit-to-stand maneuver, is (i) reduced on Day1 at 5050 m compared to 520 m, (ii) is improved after 6 days at 5050 m, and (iii) is less impaired during re-exposure to 5050 m after 7 days at 520 m compared to Cycle1. Participants spent 4-8 h/day at 5050 m and slept at 2900 m similar to real-life working shifts. High/low ARI indicate impaired/intact CA, respectively. With the sit-to-stand at 520 m, mean (95% CI) in ΔMAP and ΔMCAv were − 26% (− 41 to − 10) and − 13% (− 19 to − 7), P < 0.001 both comparisons; mean ± SD in ARI was 0.58 ± 2.44Δ%/Δ%, respectively. On Day1 at 5050 m, ARI worsened compared to 520 m (3.29 ± 2.42Δ%/Δ%), P = 0.006 but improved with acclimatization (1.44 ± 2.43Δ%/Δ%, P = 0.039). ARI was less affected during re-exposure to 5050 m (1.22 ± 2.52Δ%/Δ%, P = 0.027 altitude-induced change between sojourns). This study showed that CA (i) is impaired during acute HA exposure, (ii) improves with living high, working higher and (iii) is ameliorated during re-exposure to HA

Extravascular lung water and cardiac function assessed by echocardiography in healthy lowlanders during repeated very high-altitude exposure

Background High-altitude pulmonary edema is associated with elevated systolic pulmonary artery pressure (sPAP) and increased extravascular lung water (EVLW). We investigated sPAP and EVLW during repeated exposures to high altitude (HA). Methods Healthy lowlanders underwent two identical 7-day HA-cycles, where subjects slept at 2900 m and spent 4–8 h daily at 5050 m, separated by a weeklong break at low altitude (LA). Echocardiography and EVLW by B-lines were measured at 520 m (baseline, LA1), on day one, two and six at 5050 m (HA1–3) and after descent (LA2). Results We included 21 subjects (median 25 years, body mass index 22 kg/m2, SpO2 98%). SPAP rose from 21 mmHg at LA1 to 38 mmHg at HA1, decreased to 30 mmHg at HA3 (both p < 0.05 vs LA1) and normalized at 20 mmHg at LA2 (p = ns vs LA1). B-lines increased from 0 at LA1 to 6 at HA2 and 7 at HA3 (both p < 0.05 vs LA1) and receded to 1 at LA2 (p = ns vs LA1). Overall, in cycle two, sPAP did not differ (mean difference (95% confidence interval) −0.2(−2.3 to 1.9) mmHg, p = 0.864) but B-lines were more prevalent (+2.3 (1.4–3.1), p < 0.001) compared to cycle 1. Right ventricular systolic function decreased significantly but minimally at 5050 m. Conclusions Exposure to 5050 m induced a rapid increase in sPAP. B-lines rose during prolonged exposures to 5050 m, despite gradual decrease in sPAP, indicating excessive hydrostatic pressure might not be solely responsible for EVLW-development. Repeated HA-exposure had no acclimatization effect on EVLW. This may affect workers needing repetitive ascents to altitude and could indicate greater B-line development upon repeated exposure

The Brain in Motion II Study: study protocol for a randomized controlled trial of an aerobic exercise intervention for older adults at increased risk of dementia

Abstract Background There remains no effective intervention capable of reversing most cases of dementia. Current research is focused on prevention by addressing risk factors that are shared between cardiovascular disease and dementia (e.g., hypertension) before the cognitive, functional, and behavioural symptoms of dementia manifest. A promising preventive treatment is exercise. This study describes the methods of a randomized controlled trial (RCT) that assesses the effects of aerobic exercise and behavioural support interventions in older adults at increased risk of dementia due to genetic and/or cardiovascular risk factors. The specific aims are to determine the effect of aerobic exercise on cognitive performance, explore the biological mechanisms that influence cognitive performance after exercise training, and determine if changes in cerebrovascular physiology and function persist 1 year after a 6-month aerobic exercise intervention followed by a 1-year behavioural support programme (at 18 months). Methods We will recruit 264 participants (aged 50–80 years) at elevated risk of dementia. Participants will be randomly allocated into one of four treatment arms: (1) aerobic exercise and health behaviour support, (2) aerobic exercise and no health behaviour support, (3) stretching-toning and health behaviour support, and (4) stretching-toning and no health behaviour support. The aerobic exercise intervention will consist of three supervised walking/jogging sessions per week for 6 months, whereas the stretching-toning control intervention will consist of three supervised stretching-toning sessions per week also for 6 months. Following the exercise interventions, participants will receive either 1 year of ongoing telephone behavioural support or no telephone support. The primary aim is to determine the independent effect of aerobic exercise on a cognitive composite score in participants allocated to this intervention compared to participants allocated to the stretching-toning group. The secondary aims are to examine the effects of aerobic exercise on a number of secondary outcomes and determine whether aerobic exercise-related changes persist after a 1-year behavioural support programme (at 18 months). Discussion This study will address knowledge gaps regarding the underlying mechanisms of the pro-cognitive effects of exercise by examining the potential mediating factors, including cerebrovascular/physiological, neuroimaging, sleep, and genetic factors that will provide novel biologic evidence on how aerobic exercise can prevent declines in cognition with ageing. Trial registration ClinicalTrials.gov NCT03035851 . Registered on 30 January 201

Effects on Cognitive Functioning of Acute, Subacute and Repeated Exposures to High Altitude

Neurocognitive functions are affected by high altitude, however the altitude effects of acclimatization and repeated exposures are unclear. We investigated the effects of acute, subacute and repeated exposure to 5,050 m on cognition among altitude-naïve participants compared to control subjects tested at low altitude. Twenty-one altitude-naïve individuals (25.3 ± 3.8 years, 13 females) were exposed to 5,050 m for 1 week ( and re-exposed after a week of rest at sea-level (). Baseline (BL, 520 m), acute (Day 1, HA1) and acclimatization (Day 6, HA6, 5,050 m) measurements were taken in both cycles. Seventeen control subjects (24.9 ± 2.6 years, 12 females) were tested over a similar period in Calgary, Canada (1,103 m). The Reaction Time (RTI), Attention Switching Task (AST), Rapid Visual Processing (RVP) and One Touch Stockings of Cambridge (OTS) tasks were administered and outcomes were expressed in milliseconds/frequencies. Lake Louise Score (LLS) and blood oxygen saturation (SpO) were recorded. In both cycles, no significant changes were found with acute exposure on the AST total score, mean latency and SD. Significant changes were found upon acclimatization solely in the altitude group, with improved AST Mean Latency [HA1 (588 ± 92) vs. HA6 (526 ± 91), < 0.001] and Latency SD [HA1 (189 ± 86) vs. HA6 (135 ± 65), < 0.001] compared to acute exposure, in . No significant differences were present in the control group. When entering Acute SpO (HA1-BL), Acclimatization SpO (HA6-BL) and LLS score as covariates for both cycles, the effects of acclimatization on AST outcomes disappeared indicating that the changes were partially explained by SpO and LLS. The changes in AST Mean Latency [ΔBL (-61.2 ± 70.2) vs. ΔHA6 (-28.0 ± 58), = 0.005] and the changes in Latency SD [ΔBL (-28.4 ± 41.2) vs. ΔHA6 (-0.2235 ± 34.8), = 0.007] across the two cycles were smaller with acclimatization. However, the percent changes did not differ between cycles. These results indicate independent effects of altitude across repeated exposures. Selective and sustained attention are impaired at altitude and improves with acclimatization.The observed changes are associated, in part, with AMS score and SpO. The gains in cognition with acclimatization during a first exposure are not carried over to repeated exposures

Effect of Acute, Subacute, and Repeated Exposure to High Altitude (5050 m) on Psychomotor Vigilance

Aim: High altitude (HA) hypoxia may affect cognitive performance and sleep quality. Further, vigilance is reduced following sleep deprivation. We investigated the effect on vigilance, actigraphic sleep indices, and their relationships with acute mountain sickness (AMS) during very HA exposure, acclimatization, and re-exposure.Methods: A total of 21 healthy altitude-naive individuals (25 ± 4 years; 13 females) completed 2 cycles of altitude exposure separated by 7 days at low altitude (LA, 520 m). Participants slept at 2900 m and spent the day at HA, (5050 m). We report acute altitude exposure on Day 1 (LA vs. HA1) and after 6 days of acclimatization (HA1 vs. HA6). Vigilance was quantified by reaction speed in the 10-min psychomotor vigilance test reaction speed (PVT-RS). AMS was evaluated using the Environmental Symptoms Questionnaire Cerebral Score (AMS-C score). Nocturnal rest/activity was recorded to estimate sleep duration using actigraphy.Results: In Cycle 1, PVT-RS was slower at HA1 compared to LA (4.1 ± 0.8 vs. 4.5 ± 0.6 s-1, respectively, p = 0.029), but not at HA6 (4.6 ± 0.7; p &gt; 0.05). In Cycle 2, PVT-RS at HA1 (4.6 ± 0.7) and HA6 (4.8 ± 0.6) were not different from LA (4.8 ± 0.6, p &gt; 0.05) and significantly greater than corresponding values in Cycle 1. In both cycles, AMS scores were higher at HA1 than at LA and HA6 (p &lt; 0.05). Estimated sleep durations (TST) at LA, 1st and 5th nights were 431.3 ± 28.7, 418.1 ± 48.6, and 379.7 ± 51.4 min, respectively, in Cycle 1 and they were significantly reduced during acclimatization exposures (LA vs. 1st night, p &gt; 0.05; LA vs. 5th night, p = 0.012; and 1st vs. 5th night, p = 0.054). LA, 1st and 5th nights TST in Cycle 2 were 477.5 ± 96.9, 430.9 ± 34, and 341.4 ± 32.2, respectively, and we observed similar deteriorations in TST as in Cycle 1 (LA vs. 1st night, p &gt; 0.05; LA vs. 5th night, p = 0.001; and 1st vs. 5th night, p &lt; 0.0001). At HA1, subjects who reported higher AMS-C scores exhibited slower PVT-RS (r = -0.56; p &lt; 0.01). Subjects with higher AMS-C scores took longer time to react to the stimuli during acute exposure (r = 0.62, p &lt; 0.01) during HA1 of Cycle 1.Conclusion: Acute exposure to HA reduces the PVT-RS. Altitude acclimatization over 6 days recovers the reaction speed and prevents impairments during subsequent altitude re-exposure after 1 week spent near sea level. However, acclimatization does not lead to improvement in total sleep time during acute and subacute exposures

Differential effects of high-altitude exposure on markers of oxidative stress, antioxidant capacity, and iron profiles

High-altitude (HA) exposure may stimulate significant physiological and molecular changes, resulting in HA-related illnesses. HA may impact oxidative stress, antioxidant capacity, and iron homeostasis, yet it is unclear how both repeated exposure and HA acclimatization may modulate such effects. Therefore, we assessed the effects of weeklong repeated daily HA exposure (2,900–5,050 m) in altitude-naïve individuals ( n = 21 individuals, 13 females, mean ± SD, 25.3 ± 3.7 yr) to mirror the working schedule of HA workers ( n = 19 individuals, all males, 41.1 ± 9.4 yr) at the Atacama Large Millimeter Array (ALMA) Observatory (San Pedro de Atacama, Chile). Markers of oxidative stress, antioxidant capacity, and iron homeostasis were measured in blood plasma. Levels of protein oxidation ( P < 0.001) and catalase activity ( P = 0.023) increased and serum iron ( P < 0.001), serum ferritin ( P < 0.001), and transferrin saturation ( P < 0.001) levels decreased with HA exposure in both groups. HA workers had lower levels of oxidative stress, and higher levels of antioxidant capacity, iron supply, and hemoglobin concentration as compared with altitude-naïve individuals. On a second week of daily HA exposure, changes in levels of protein oxidation, glutathione peroxidase, and nitric oxide metabolites were lower as compared with the first week in altitude-naïve individuals. These results indicate that repeated exposure to HA may significantly alter oxidative stress and iron homeostasis, and the degree of such changes may be dependent on if HA is visited naïvely or routinely. Further studies are required to fully elucidate differences in HA-induced changes in oxidative stress and iron homeostasis profiles among visitors of HA