Performance Evaluation of a New Sport Watch in Sleep Tracking: A Comparison against Overnight Polysomnography in Young Adults.

Introduction: This study aimed to validate the ability of a prototype sport watch (Polar Electro Oy, FI) to recognize wake and sleep states in two trials with and without an interval training session (IT) 6 h prior to bedtime. Methods: Thirty-six participants completed this study. Participants performed a maximal aerobic test and three polysomnography (PSG) assessments. The first night served as a device familiarization night and to screen for sleep apnea. The second and third in-home PSG assessments were counterbalanced with/without IT. Accuracy and agreement in detecting sleep stages were calculated between PSG and the prototype. Results: Accuracy for the different sleep stages (REM, N1 and N2, N3, and awake) as a true positive for the nights without exercise was 84 ± 5%, 64 ± 6%, 81 ± 6%, and 91 ± 6%, respectively, and for the nights with exercise was 83 ± 7%, 63 ± 8%, 80 ± 7%, and 92 ± 6%, respectively. The agreement for the sleep night without exercise was 60.1 ± 8.1%, k = 0.39 ± 0.1, and with exercise was 59.2 ± 9.8%, k = 0.36 ± 0.1. No significant differences were observed between nights or between the sexes. Conclusion: The prototype showed better or similar accuracy and agreement to wrist-worn consumer products on the market for the detection of sleep stages with healthy adults. However, further investigations will need to be conducted with other populations.

Internal consistency and reliability of the lifetime and modified current cognitive activity questionnaires and their association with cognitive performance: a six-year follow up of the Brain in Motion study.

INTRODUCTION: Cognitive activity questionnaires could provide insight into neurocognitive reserve. The Lifetime Cognitive Activities Questionnaire (LCAQ) assesses cognitive activities at four stages of life. The Modified Current Cognitive Activities Questionnaire (CCAQ) assesses current cognitive activities. We examined the construct validity, internal consistency, test-retest reliability, and stability of these questionnaires throughout the Brain in Motion (BIM) study and their relationship with cognitive performance. METHODS: The LCAQ, Montreal Cognitive Assessment (MoCA), and neuropsychological battery were administered at the initial pre-intervention and six-year follow-up. The CCAQ was administered at five timepoints. Construct validity of the CCAQ/LCAQ was assessed using proxies of cognitive engagement (educational attainment and the North American Adult Reading Test [NAART]). Cronbach alpha analysis determined internal consistency. LCAQ reliability was established by comparing the pre-intervention and six-year follow-up. CCAQ reliability was determined by comparing both pre-intervention assessments, correlations throughout BIM determined stability. A multiple linear regression investigated the associations between cognitive engagement and cognitive domains derived from a principal component analysis. RESULTS: MoCA scores at the initial pre-intervention (27.49 ± 1.46) and six-year follow up (26.53 ± 2.08). The LCAQ and CCAQ correlated with educational attainment and the NAART. The LCAQ (n = 266) produced an alpha of 0.90 (20 items). The CCAQ (n = 261) resulted in an alpha of 0.71 (25 items). LCAQ scores (n = 94) at the initial pre-intervention and six-year follow-up were correlated. CCAQ (n = 94) scores at the initial pre-intervention correlated with scores at all five other timepoints. The multiple linear regression revealed associations between the CCAQ and verbal memory/attention. The NAART was associated with processing speed, concept formation, and verbal memory/attention. CONCLUSIONS: In the absence of cognitive decline, these questionnaires exhibit significant construct validity, internal consistency, test-retest reliability, and the CCAQ displayed stability. The NAART and CCAQ were associated with neuropsychological performance. Our findings support future use of these questionnaires and exemplify the neuroprotective role of cognitive engagement.

Blood pressure trajectory of inpatient stroke rehabilitation patients from the Determining Optimal Post-Stroke Exercise (DOSE) trial over the first 12 months post-stroke.

Background: High blood pressure (BP) is the primary risk factor for recurrent strokes. Despite established clinical guidelines, some stroke survivors exhibit uncontrolled BP over the first 12 months post-stroke. Furthermore, research on BP trajectories in stroke survivors admitted to inpatient rehabilitation hospitals is limited. Exercise is recommended to reduce BP after stroke. However, the effect of high repetition gait training at aerobic intensities (>40% heart rate reserve; HRR) during inpatient rehabilitation on BP is unclear. We aimed to determine the effect of an aerobic gait training intervention on BP trajectory over the first 12 months post-stroke. Methods: This is a secondary analysis of the Determining Optimal Post-Stroke Exercise (DOSE) trial. Participants with stroke admitted to inpatient rehabilitation hospitals were recruited and randomized to usual care (n = 24), DOSE1 (n = 25; >2,000 steps, 40-60% HRR for >30 min/session, 20 sessions over 4 weeks), or DOSE2 (n = 25; additional DOSE1 session/day) groups. Resting BP [systolic (SBP) and diastolic (DBP)] was measured at baseline (inpatient rehabilitation admission), post-intervention (near inpatient discharge), 6- and 12-month post-stroke. Linear mixed-effects models were used to examine the effects of group and time (weeks post-stroke) on SBP, DBP and hypertension (≥140/90 mmHg; ≥130/80 mmHg, if diabetic), controlling for age, stroke type, and baseline history of hypertension. Results: No effect of intervention group on SBP, DBP, or hypertension was observed. BP increased from baseline to 12-month post-stroke for SBP (from [mean ± standard deviation] 121.8 ± 15.0 to 131.8 ± 17.8 mmHg) and for DBP (74.4 ± 9.8 to 78.5 ± 10.1 mmHg). The proportion of hypertensive participants increased from 20.8% (n = 15/72) to 32.8% (n = 19/58). These increases in BP were statistically significant: an effect [estimation (95%CI), value of p] of time was observed on SBP [0.19 (0.12-0.26) mmHg/week, p < 0.001], DBP [0.09 (0.05-0.14) mmHg/week, p < 0.001], and hypertension [OR (95%CI): 1.03 (1.01-1.05), p = 0.010]. A baseline history of hypertension was associated with higher SBP by 13.45 (8.73-18.17) mmHg, higher DBP by 5.57 (2.02-9.12) mmHg, and 42.22 (6.60-270.08) times the odds of being hypertensive at each timepoint, compared to those without. Conclusion: Blood pressure increased after inpatient rehabilitation over the first 12 months post-stroke, especially among those with a history of hypertension. The 4-week aerobic gait training intervention did not influence this trajectory.

Acute high altitude exposure, acclimatization and re-exposure on nocturnal breathing.

Background: Effects of prolonged and repeated high-altitude exposure on oxygenation and control of breathing remain uncertain. We hypothesized that prolonged and repeated high-altitude exposure will improve altitude-induced deoxygenation and breathing instability. Methods: 21 healthy lowlanders, aged 18-30y, underwent two 7-day sojourns at a high-altitude station in Chile (4-8 hrs/day at 5,050 m, nights at 2,900 m), separated by a 1-week recovery period at 520 m. Respiratory sleep studies recording mean nocturnal pulse oximetry (SpO2), oxygen desaturation index (ODI, >3% dips in SpO2), breathing patterns and subjective sleep quality by visual analog scale (SQ-VAS, 0-100% with increasing quality), were evaluated at 520 m and during nights 1 and 6 at 2,900 m in the 1st and 2nd altitude sojourn. Results: At 520 m, mean ± SD nocturnal SpO2 was 94 ± 1%, ODI 2.2 ± 1.2/h, SQ-VAS 59 ± 20%. Corresponding values at 2,900 m, 1st sojourn, night 1 were: SpO2 86 ± 2%, ODI 23.4 ± 22.8/h, SQ-VAS 39 ± 23%; 1st sojourn, night 6: SpO2 90 ± 1%, ODI 7.3 ± 4.4/h, SQ-VAS 55 ± 20% (p < 0.05, all differences within corresponding variables). Mean differences (Δ, 95%CI) in acute effects (2,900 m, night 1, vs 520 m) between 2nd vs 1st altitude sojourn were: ΔSpO2 0% (-1 to 1), ΔODI -9.2/h (-18.0 to -0.5), ΔSQ-VAS 10% (-6 to 27); differences in acclimatization (changes night 6 vs 1), between 2nd vs 1st sojourn at 2,900 m were: ΔSpO2 -1% (-2 to 0), ΔODI 11.1/h (2.5 to 19.7), ΔSQ-VAS -15% (-31 to 1). Conclusion: Acute high-altitude exposure induced nocturnal hypoxemia, cyclic deoxygenations and impaired sleep quality. Acclimatization mitigated these effects. After recovery at 520 m, repeated exposure diminished high-altitude-induced deoxygenation and breathing instability, suggesting some retention of adaptation induced by the first altitude sojourn while subjective sleep quality remained similarly impaired.

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.

Aerobic exercise training in older men and women-Cerebrovascular responses to submaximal exercise: Results from the Brain in Motion study.

Physical inactivity is a leading modifiable risk factor for cardiovascular and cerebrovascular disease, cognitive dysfunction, and global mortality. Regular exercise might mitigate age-related declines in cardiovascular and cerebrovascular function. In this study, we hypothesize that a 6-month aerobic exercise intervention will lead to a decrease in cerebrovascular resistance index (CVRi) and to an increase in cerebral blood flow (CBF) and cerebrovascular conductance index (CVCi) during two submaximal exercise workloads (40% VO2 max and 65 W), intensities that have been shown to be comparable to activities of daily life. Two hundred three low-active healthy men and women enrolled in the Brain in Motion study, completed a 6-month exercise intervention and underwent submaximal and maximal tests pre-/post-intervention. The intervention improved the gas exchange threshold and maximal oxygen consumption (VO2 max), with no change in heart rate at VO2 max, during the treadmill VO2 max test. Heart rate and CVRi decreased from pre-intervention values during both relative (40% VO2 max) and absolute (65 W) submaximal exercise tests. Blood flow velocity in the middle cerebral artery and CVCi increased post-intervention during 40% VO2 max and 65 W. Changes in mean arterial pressure were found only during the absolute component (65 W). Our study demonstrates that aerobic exercise improves not only cardiorespiratory indices but also cerebrovascular function at submaximal workloads which may help to mitigate age-related declines in everyday life. Investigation of the mechanisms underlying the decline in cardiovascular and cerebrovascular capacity with aging has important implications for the maintenance of health and continued independence of older adults.

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.

Impact of intermittent hypoxia on human vascular responses during sleep.

Exposure to intermittent hypoxia (IH) ≥15 times per hour is believed to be the primary mechanism for the increased risk of cerebrovascular and cardiovascular disease in patients with moderate to severe sleep apnea. Human experimental models of IH used to investigate this link have been predominantly employed during wakefulness, which limits extrapolation of findings to sleep apnea where IH occurs during sleep. Moreover, how IH impacts vascular regulation during sleep has not been measured quantitatively. Therefore, the objective of this study was to assess the impact sleep accompanied by IH on vascular responses to hypoxia and hypercapnia during sleep. Ten males performed two randomly scheduled 6-h overnight sleep studies. One sleep study was performed in room air (normoxia) and the other sleep study was performed during isocapnic IH (60 s hypoxia-60 s normoxia). On each night, cerebrovascular (peak blood velocity through the middle cerebral artery (V¯P); transcranial Doppler ultrasound) and cardiovascular (blood pressure, heart rate) responses to hypoxia and hypercapnia were measured before sleep onset (PM-Awake), within the first 2 h of sleep (PM-Asleep), in the 5th (out of 6) hours of sleep (AM-Asleep) and after being awoken in the morning (AM-Awake). Sleep accompanied by IH had no impact on the V¯P and blood pressure responses to hypoxia and hypercapnic at any timepoint (p ≥ 0.103 for all responses). However, the AM-Awake heart rate response to hypoxia was greater following sleep in IH compared to sleep in normoxia. Independent of the sleep environment, the V¯P response to hypoxia and hypercapnia were reduced during sleep. In conclusion, cerebral blood flow responses are reduced during sleep compared to wakefulness, but 6 h of sleep accompanied by IH does not alter cerebrovascular and cardiovascular response to hypoxia and hypercapnia during wakefulness or sleep in healthy young humans. However, it is likely that longer exposure to IH during sleep (i.e., days-to-weeks) is required to better elucidate IH's impact on vascular regulation in humans.

Diagnosing Alzheimer's Disease from Circulating Blood Leukocytes Using a Fluorescent Amyloid Probe.

BACKGROUND: Toxic amyloid-ß (Aß) peptides aggregate into higher molecular weight assemblies and accumulate not only in the extracellular space, but also in the walls of blood vessels in the brain, increasing their permeability, and promoting immune cell migration and activation. Given the prominent role of the immune system, phagocytic blood cells may contact pathological brain materials. OBJECTIVE: To develop a novel method for early Alzheimer's disease (AD) detection, we used blood leukocytes, that could act as "sentinels" after trafficking through the brain microvasculature, to detect pathological amyloid by labelling with a conformationally-sensitive fluorescent amyloid probe and imaging with confocal spectral microscopy. METHODS: Formalin-fixed peripheral blood mononuclear cells (PBMCs) from cognitively healthy control (HC) subjects, mild cognitive impairment (MCI) and AD patients were stained with the fluorescent amyloid probe K114, and imaged. Results were validated against cerebrospinal fluid (CSF) biomarkers and clinical diagnosis. RESULTS: K114-labeled leukocytes exhibited distinctive fluorescent spectral signatures in MCI/AD subjects. Comparing subjects with single CSF biomarker-positive AD/MCI to negative controls, our technique yielded modest AUCs, which improved to the 0.90 range when only MCI subjects were included in order to measure performance in an early disease state. Combining CSF Aß42 and t-Tau metrics further improved the AUC to 0.93. CONCLUSION: Our method holds promise for sensitive detection of AD-related protein misfolding in circulating leukocytes, particularly in the early stages of disease.

Effects of changes in end-tidal PO2 and PCO2 on neural responses during rest and sustained attention.

Impairments of cognitive function during alterations in arterial blood gases (e.g., high-altitude hypoxia) may result from the disruption of neurovascular coupling; however, the link between changes in arterial blood gases, cognition, and cerebral blood flow (CBF) is poorly understood. To interrogate this link, we developed a multimodal empirical strategy capable of monitoring neural correlates of cognition and CBF simultaneously. Human participants performed a sustained attention task during hypoxia, hypercapnia, hypocapnia, and normoxia while electroencephalographic (EEG) activity and CBF (middle and posterior cerebral arteries; transcranial Doppler ultrasound) were simultaneously measured. The protocol alternated between rest and engaging in a visual target detection task that required participants to monitor a sequence of brief-duration colored circles and detect infrequent, longer duration circles (targets). The target detection task was overlaid on a large, circular checkerboard that provided robust visual stimulation. Spectral decomposition and event-related potential (ERP) analyses were applied to the EEG data to investigate spontaneous and task-specific fluctuations in neural activity. There were three main sets of findings: (1) spontaneous alpha oscillatory activity was modulated as a function of arterial CO2 (hypocapnia and hypercapnia), (2) task-related neurovascular coupling was disrupted by all arterial blood gas manipulations, and (3) changes in task-related alpha and theta band activity and attenuation of the P3 ERP component amplitude were observed during hypocapnia. Since alpha and theta are linked with suppression of visual processing and executive control and P3 amplitude with task difficulty, these data suggest that transient arterial blood gas changes can modulate multiple stages of cognitive information processing.

Impact of nocturnal oxygen and CPAP on the ventilatory response to hypoxia in OSA patients free of overt cardiovascular disease.

A primary characteristic of obstructive sleep apnea (OSA) is chronic exposure to intermittent hypoxia (IH) due to repeated upper airway obstruction. Chronic IH exposure is believed to increase OSA severity over time by enhancing the acute ventilatory response to hypoxia (AHVR), thus promoting ventilatory overshoot when apnea ends and perpetuation of apnea during sleep. Continuous positive airway pressure (CPAP), the gold-standard treatment of OSA, reduces the AHVR, believed to result from correction of IH. However, CPAP also corrects ancillary features of OSA such as intermittent hypercapnia, negative intrathoracic pressure and surges in sympathetic activity, which may also contribute to the reduction in AHVR. Therefore, the objective of this study was to investigate the impact of nocturnal oxygen therapy (to remove IH only) and CPAP (to correct IH and ancillary features of OSA) on AHVR in newly diagnosed OSA patients. Fifty-two OSA patients and twenty-two controls were recruited. The AHVR was assessed using a 5 min iscopanic-hypoxic challenge before, and after, treatment of OSA by nocturnal oxygen therapy and CPAP. Following baseline measurements, OSA patients were randomly assigned to nocturnal oxygen therapy (Oxygen, n = 26) or no treatment (Air; n = 26). The AHVR was re-assessed following two weeks of oxygen therapy or no treatment, after which all patients were treated with CPAP. The AHVR was quantified following ~4 weeks of adherent CPAP therapy (n = 40). Both nocturnal oxygen and CPAP treatments improved hypoxemia (p < 0.05), and, as expected, nocturnal oxygen therapy did not completely abolish respiratory events (i.e., apneas/hypopneas). Averaged across all OSA patients, nocturnal oxygen therapy did not change AHVR from baseline to post-oxygen therapy. Similarly, the AHVR was not altered pre- and post-CPAP (p > 0.05). However, there was a significant decrease in AHVR with both nocturnal oxygen therapy and CPAP in patients in the highest OSA severity quartile (p < 0.05). Nocturnal oxygen therapy and CPAP both reduce the AHVR in patients with the most severe OSA. Therefore, IH appears to be the primary mechanism producing ventilatory instability in patients with severe OSA via enhancement of the AHVR.

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.

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 2017.

Impact of obstructive sleep apnoea and intermittent hypoxia on blood rheology: a translational study.

BACKGROUND: Haemorheological alterations are reported in obstructive sleep apnoea (OSA) and reversed with continuous positive airway pressure (CPAP), observations potentially explained by intermittent hypoxia (IH)-induced oxidative stress. Our objective was to investigate whether IH causes haemorheological alterations via oxidative stress. METHODS: Wistar rats were exposed to normoxia (n=7) or IH (n=8) for 14 days. 23 moderate-to-severe OSA patients were assessed at three time-points: baseline, after randomisation to either 2 weeks of nocturnal oxygen (n=13) or no treatment (n=10) and after 1 month of CPAP treatment (n=17). Furthermore, an OSA-free control group (n=13) was assessed at baseline and after time-matched follow-up. We measured haemorheological parameters (haematocrit, blood viscosity, plasma viscosity (rats only), erythrocyte aggregation and deformability (humans only)) and redox balance (superoxide dismutase (SOD), glutathione peroxidase, protein oxidation (advanced oxidation protein products (AOPPs)) and lipid peroxidation (malondialdehyde)). We also tested the haemorheological sensitivity of erythrocytes to reactive oxygen species (ROS) in our human participants using the oxidant t-butyl hydroperoxide (TBHP). RESULTS: In rats, IH increased blood viscosity by increasing haematocrit without altering the haemorheological properties of erythrocytes. IH also reduced SOD activity and increased AOPPs. In humans, baseline haemorheological properties were similar between patients and control participants, and properties were unaltered following oxygen and CPAP, except erythrocyte deformability was reduced following oxygen therapy. Redox balance was comparable between patients and control participants. At baseline, TBHP induced a greater reduction of erythrocyte deformability in patients while CPAP reduced TBHP-induced increase in aggregation strength. CONCLUSIONS: IH and OSA per se do not cause haemorheological alterations despite the presence of oxidative stress or higher sensitivity to ROS, respectively.

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.

Association of sleep spindle characteristics with executive functioning in healthy sedentary middle-aged and older adults.

To determine the relationship between sleep spindle characteristics (density, power and frequency), executive functioning and cognitive decline in older adults, we studied a convenience subsample of healthy middle-aged and older participants of the Brain in Motion study. Participants underwent a single night of unattended in-home polysomnography with neurocognitive testing carried out shortly afterwards. Spectral analysis of the EEG was performed to derive spindle characteristics in both central and frontal derivations during non-rapid eye movement (NREM) Stage 2 and 3. Multiple linear regressions were used to examine associations between spindle characteristics and cognitive outcomes, with age, body mass index (BMI), periodic limb movements index (PLMI) and apnea hypopnea index (AHI) as covariates. NREM Stage 2 total spindle density was significantly associated with executive functioning (central: ß = .363, p = .016; frontal: ß = .408, p = .004). NREM Stage 2 fast spindle density was associated with executive functioning (central: ß = .351, p = .022; frontal: ß = .380, p = .009) and Montreal Cognitive Assessment score (MoCA, central: ß = .285, p = .037; frontal: ß = .279, p = .032). NREM Stage 2 spindle frequency was also associated with MoCA score (central: ß = .337, p = .013). Greater spindle density and fast spindle density were associated with better executive functioning and less cognitive decline in our study population. Our cross-sectional design cannot infer causality. Longitudinal studies will be required to assess the ability of spindle characteristics to predict future cognitive status.

Genetic Risk, Vascular Function, and Subjective Cognitive Complaints Predict Objective Cognitive Function in Healthy Older Adults: Results From the Brain in Motion Study.

Aging is associated with subjective memory complaints. Approximately half of those with subjective memory complaints have objective cognitive impairment. Previous studies have provided evidence of an association between genetic risk for Alzheimer's disease (AD) and dementia progression. Also, aging is a significant risk factor for vascular pathology that may underlie at least some of the cognitive changes. This study investigates the relative contribution of subjective cognitive complaints (SCC), vascular function, and genetic risk for dementia in predicting objective cognitive performance. Multiple regression and relative importance analysis were used to investigate the relative contribution of vascular function, self-reported SCC, and dementia genetic risk, in predicting objective cognition in a sample of 238 healthy community-dwelling older adults. Age, sex, premorbid cognitive abilities, subjective verbal memory complaints, higher cerebrovascular blood flow during submaximal exercise, and certain dementia risk alleles were significant predictors of worse objective verbal memory performance (p < 0.001, R 2 = 35.2-36.4%). Using relative importance analysis, subjective verbal memory complaints, and certain dementia risk alleles contributed more variance than cerebrovascular measures. These results suggest that age-related changes in memory in healthy older adults can be predicted by subjective memory complaints, genetic risk, and to a lesser extent, cerebrovascular function.

Higher Doses Improve Walking Recovery During Stroke Inpatient Rehabilitation.

BACKGROUND AND PURPOSE: We investigated the effect of higher therapeutic exercise doses on walking during inpatient rehabilitation, typically commencing 1 to 4 weeks poststroke. METHODS: This phase II, blinded-assessor, randomized controlled trial recruited from 6 Canadian inpatient rehabilitation units, between 2014 and 2018. Subjects (n=75; 25/group) were randomized into: control (usual care) physical therapy: typically, 1 hour, 5 days/week; Determining Optimal Post-Stroke Exercise (DOSE1): 1 hour, 5 days/week, more than double the intensity of Control (based on aerobic minutes and walking steps); and DOSE2: 2 hours, 5 days/week, more than quadruple the intensity of Control, each for 4 weeks duration. The primary outcome, walking endurance at completion of the 4-week intervention (post-evaluation), was compared across these groups using linear regression. Secondary outcomes at post-evaluation, and longitudinal outcomes at 6 and 12-month evaluations, were also analyzed. RESULTS: Both DOSE1 (mean change 61 m [95% CI, 9-113], P=0.02) and DOSE2 (mean change 58 m, 6-110, P=0.03) demonstrated greater walking endurance compared with Control at the post-evaluation. Significant improvements were also observed with DOSE2 in gait speed (5-m walk), and both DOSE groups in quality of life (EQ-5D-5 L) compared with Control. Longitudinal analyses revealed that improvements in walking endurance from the DOSE intervention were retained during the 1-year follow-up period over usual care. CONCLUSIONS: This study provides the first preliminary evidence that patients with stroke can improve their walking recovery and quality of life with higher doses of aerobic and stepping activity within a critical time period for neurological recovery. Furthermore, walking endurance benefits achieved from a 4-week intervention are retained over the first-year poststroke. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01915368.

Aerobic exercise improves cognition and cerebrovascular regulation in older adults.

OBJECTIVE: To test the hypothesis that aerobic exercise is associated with improvements in cognition and cerebrovascular regulation, we enrolled 206 healthy low-active middle-aged and older adults (mean ± SD age 65.9 ± 6.4 years) in a supervised 6-month aerobic exercise intervention and assessed them before and after the intervention. METHODS: The study is a quasi-experimental single group pre/postintervention study. Neuropsychological tests were used to assess cognition before and after the intervention. Transcranial Doppler ultrasound was used to measure cerebral blood flow velocity. Cerebrovascular regulation was assessed at rest, during euoxic hypercapnia, and in response to submaximal exercise. Multiple linear regression was used to examine the association between changes in cognition and changes in cerebrovascular function. RESULTS: The intervention was associated with improvements in some cognitive domains, cardiorespiratory fitness, and cerebrovascular regulation. Changes in executive functions were negatively associated with changes in cerebrovascular resistance index (CVRi) during submaximal exercise (ß = -0.205, p = 0.013), while fluency improvements were positively associated with changes in CVRi during hypercapnia (ß = 0.106, p = 0.03). CONCLUSION: The 6-month aerobic exercise intervention was associated with improvements in some cognitive domains and cerebrovascular regulation. Secondary analyses showed a novel association between changes in cognition and changes in cerebrovascular regulation during euoxic hypercapnia and in response to submaximal exercise.

Impact of aerobic exercise, sex, and metabolic syndrome on markers of oxidative stress: results from the Brain in Motion study.

Oxidative stress may be involved in disease pathology and dependent on both modifiable and nonmodifiable factors. This study aimed to assess exercise-induced changes in markers of oxidative stress among older, sedentary adults and to determine the effects of metabolic syndrome (MetS) status, aerobic capacity, age, sex, and weight on these biomarkers. Two hundred and six participants (means ± SE; 66.8 ± 6.4 yr, 104 women) of the Brain in Motion study underwent a 6-mo aerobic exercise intervention. At three time points, venous blood samples were collected and analyzed for markers of oxidative stress [advanced oxidation protein products (AOPP), malondialdehyde (MDA), 3-nitrotyrosine (3-NT) and antioxidant status: catalase, uric acid (UA), superoxide dismutase (SOD), and ferric-reducing ability of plasma (FRAP)]. AOPP levels significantly decreased after 6 mo of aerobic exercise (P = 0.003). This decrease was not modified by MetS status (P = 0.183). Subjects with MetS possessed significantly higher levels of AOPP (P < 0.001), MDA (P = 0.004), and FRAP (P = 0.049) across the intervention (months 0-6). Men possessed significantly higher levels of FRAP (P < 0.001), catalase (P = 0.023), and UA (P = 0.037) across the intervention (months 0-6). Sex-MetS status interaction analyses revealed that the effect of MetS is highly sex dependent. These findings are multifaceted because the effect of MetS status seems distinctly different between sexes, pointing to the importance of acknowledging modifiable and nonmodifiable factor differences in individuals who possess conditions where oxidative stress may be part of the etiology.NEW & NOTEWORTHY Oxidative stress is implicated in a myriad of conditions, namely cardiovascular disease risk factors. This article details the effect of aerobic exercise, sex, and metabolic syndrome on markers of oxidative stress. We conclude that 6 mo of aerobic exercise significantly decreased oxidative stress, and further, that there is an effect of metabolic syndrome status on oxidative stress and antioxidant status levels, which are highly dependent on the sex of the individual.

Cognitive Effects of Repeated Acute Exposure to Very High Altitude Among Altitude-Experienced Workers at 5050 m.

Background: We investigated altitude effects on different cognitive domains among perennial shift-workers at the Atacama Large Millimeter/submillimeter Array Observatory (5050 m), Chile. Materials and Methods: Twenty healthy male workers were recruited and assigned to either a moderate-altitude first (MAF group, Test 1: 2900 m and Test 2: 5050 m) or to a high-altitude first (HAF group, Test 1: 5050 m and Test 2: 2900 m). Test 1 was conducted at the beginning and Test 2 at the end of the shift-work week. Processing speed (RTI, reaction time), attention (AST, attention-switching task, and RVP, rapid visual processing), and executive function (OTS, One Touch Stockings of Cambridge) were assessed. Results: Of the three cognitive domains assessed, only processing speed showed altitude-at-test group interaction (RTI median five choice reaction time: F1, 17 = 6.980, [Formula: see text] = 0.291, p = 0.017). With acclimatization, there was a decrease in AST reaction latency mean (t17 = -2.155, dz = 1.086, p = 0.046), an increase in RVP accuracy (t17 = 2.733, dz = 1.398, p = 0.014), and a decrease in OTS mean latency first choice (t17 = -2.375, dz = 1.211, p = 0.03). Decreased variability in cognitive function was observed in AST reaction latency standard deviation (t17 = -2.524, dz = 1.282, p = 0.022) and in RVP response latency standard deviation (t17 = -2.35, dz = 1.177, p = 0.03) with acclimatization. At 5050 m of elevation, SpO2 was positively correlated with executive function in the MAF group (OTS problems solved on first choice: r(5) = 0.839, p = 0.018) and negatively correlated with executive function latency standard deviations in the HAF group (OTS latency to first choice standard deviation: r(10) = -0.618, p = 0.032). Conclusions: Our findings highlight the importance of acclimatization and improvement of blood oxygen level, even among high altitude-experienced workers, to optimize performance of cognitively demanding work and reduce high altitude-associated health risks.