Publications by authors named "Marc J Poulin"

101 Publications

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

Front Integr Neurosci 2020 3;14:571683. Epub 2020 Nov 3.

Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

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 ( < 0.001, = 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.
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http://dx.doi.org/10.3389/fnint.2020.571683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669615PMC
November 2020

Higher Doses Improve Walking Recovery During Stroke Inpatient Rehabilitation.

Stroke 2020 09 19;51(9):2639-2648. Epub 2020 Aug 19.

Department of Physical Therapy (T.D.K., T.L.-A., A.S., J.J.E.), University of British Columbia, Vancouver, Canada.

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], =0.02) and DOSE2 (mean change 58 m, 6-110, =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.
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http://dx.doi.org/10.1161/STROKEAHA.120.029245DOI Listing
September 2020

Aerobic exercise improves cognition and cerebrovascular regulation in older adults.

Neurology 2020 05 13;94(21):e2245-e2257. Epub 2020 May 13.

From the Department of Physiology and Pharmacology (V.G., L.L.D., A.V.T., G.A.E., M.J.P.), Hotchkiss Brain Institute (V.G., L.L.D., A.V.T., R.S.L., M.D.H., D.B.H., M.J.P.), Division of Geriatric Medicine (D.B.H.), Department of Medicine, Department of Clinical Neurosciences (V.G., L.L.D., A.V.T., M.D.H., D.B.H., M.J.P.), Libin Cardiovascular Institute of Alberta (T.J.A., M.J.P.), O'Brien Institute for Public Health (V.G., D.B.H., M.J.P.), Department of Cardiac Sciences (T.J.A.), Libin Cardiovascular Institute of Alberta, and Department of Community Health Sciences (M.D.H.), Cumming School of Medicine, Faculty of Kinesiology (M.J.P.), and Department of Psychology (R.S.L.), University of Calgary; Psychology Service (R.S.L.), Alberta Health Service, Foothills Medical Centre, Calgary; Department of Psychiatry (G.A.E.), Faculty of Medicine, and Department of Psychology and Neuroscience (G.A.E.), Faculty of Science, Dalhousie University, Halifax, Nova Scotia; and Program for Pregnancy and Postpartum Health, Physical Activity and Diabetes Laboratory (M.H.D.), Faculty of Kinesiology, Sport, and Recreation, Women and Children's Health Research Institute, Alberta Diabetes Institute, University of Alberta, Edmonton, Canada.

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 (β = -0.205, = 0.013), while fluency improvements were positively associated with changes in CVRi during hypercapnia (β = 0.106, 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.
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http://dx.doi.org/10.1212/WNL.0000000000009478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357295PMC
May 2020

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

J Sleep Res 2020 Apr 12:e13037. Epub 2020 Apr 12.

Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

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: β = .363, p = .016; frontal: β = .408, p = .004). NREM Stage 2 fast spindle density was associated with executive functioning (central: β = .351, p = .022; frontal: β = .380, p = .009) and Montreal Cognitive Assessment score (MoCA, central: β = .285, p = .037; frontal: β = .279, p = .032). NREM Stage 2 spindle frequency was also associated with MoCA score (central: β = .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.
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http://dx.doi.org/10.1111/jsr.13037DOI Listing
April 2020

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

J Appl Physiol (1985) 2020 04 27;128(4):748-756. Epub 2020 Feb 27.

Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

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 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 ( = 0.003). This decrease was not modified by MetS status ( = 0.183). Subjects with MetS possessed significantly higher levels of AOPP ( < 0.001), MDA ( = 0.004), and FRAP ( = 0.049) across the intervention (). Men possessed significantly higher levels of FRAP ( < 0.001), catalase ( = 0.023), and UA ( = 0.037) across the intervention (). 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. 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.
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http://dx.doi.org/10.1152/japplphysiol.00667.2019DOI Listing
April 2020

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

High Alt Med Biol 2019 12 25;20(4):361-374. Epub 2019 Oct 25.

Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Canada.

We investigated altitude effects on different cognitive domains among perennial shift-workers at the Atacama Large Millimeter/submillimeter Array Observatory (5050 m), Chile. Twenty healthy male workers were recruited and assigned to either a moderate-altitude first ( group, : 2900 m and : 5050 m) or to a high-altitude first ( group, : 5050 m and : 2900 m). was conducted at the beginning and 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. Of the three cognitive domains assessed, only processing speed showed altitude-at-test group interaction (RTI median five choice reaction time:  = 6.980, [Formula: see text] = 0.291,  = 0.017). With acclimatization, there was a decrease in AST reaction latency mean ( = -2.155,  1.086,  = 0.046), an increase in RVP accuracy ( = 2.733,  1.398,  = 0.014), and a decrease in OTS mean latency first choice ( = -2.375,  1.211,  = 0.03). Decreased variability in cognitive function was observed in AST reaction latency standard deviation ( = -2.524,  1.282,  = 0.022) and in RVP response latency standard deviation ( = -2.35,  1.177,  = 0.03) with acclimatization. At 5050 m of elevation, SpO was positively correlated with executive function in the group (OTS problems solved on first choice:  = 0.839,  = 0.018) and negatively correlated with executive function latency standard deviations in the group (OTS latency to first choice standard deviation:  = -0.618,  = 0.032). 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.
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http://dx.doi.org/10.1089/ham.2019.0012DOI Listing
December 2019

Effect of aerobic exercise on white matter microstructure in the aging brain.

Behav Brain Res 2019 11 4;373:112042. Epub 2019 Jul 4.

Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; O'Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada. Electronic address:

Aging is associated with decline in white matter (WM) microstructure, decreased cognitive functioning, and increased risk of Alzheimer's disease and related dementias. Recent research has identified aerobic physical exercise as a promising intervention for increasing white matter microstructure in aging, with the aim of increasing cognitive abilities, and protecting against neurodegenerative processes. However, the degree to which white matter microstructure can be protected or improved with exercise remains incompletely understood. Here, a sub-group of 25 healthy, sedentary participants (aged 57 to 86 years; M = 67.1; SD = 7.9; 11 female, 14 male) from the larger Brain in Motion Study (Tyndall et al., 2013) underwent diffusion tensor imaging (DTI) before and after a six-month aerobic exercise intervention. DTI data were analysed with FSL's Tract-Based Spatial Statistics (TBSS) to determine whether WM microstructure improved, as defined by increased fractional anisotropy (FA) and/or decreased mean diffusivity (MD), after the aerobic exercise intervention. Neither FA nor MD of the cerebral WM were significantly correlated with either age or cardiovascular fitness at baseline. Whole-brain WM mean FA decreased over the intervention while mean MD showed no significant change. Longitudinal TBSS analyses revealed decreased FA in the left uncinate fasciculus, left anterior corona radiata, left inferior fronto-occipital fasciculus, and left anterior thalamic radiation. MD increased in the left forceps major, left inferior longitudinal fasciculus, and left superior longitudinal fasciculus. Results indicate that six months of aerobic exercise in healthy, sedentary older adults was not associated with improvements in FA or MD measures of cerebral WM microstructure.
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http://dx.doi.org/10.1016/j.bbr.2019.112042DOI Listing
November 2019

Aerobic exercise increases cortisol awakening response in older adults.

Psychoneuroendocrinology 2019 05 19;103:241-248. Epub 2019 Jan 19.

University of Calgary, Department of Physiology & Pharmacology, Canada; University of Calgary Hotchkiss Brain Institute, Canada; University of Calgary, Department of Clinical Neurosciences, Canada; University of Calgary Libin Cardiovascular Institute of Alberta, Canada; University of Calgary, Department of Faculty of Kinesiology, Canada. Electronic address:

Evidence from both preclinical and clinical studies suggests aerobic exercise may dampen age-related decline in cognitive performance. Alterations in hypothalamic-pituitary-adrenal (HPA) axis function and reactivity may be a mechanism by which aerobic exercise benefits cognitive performance, and reduces perceived stress. This investigation was completed as an ancillary investigation of the Brain in Motion (BIM) study, a 6-month supervised aerobic exercise intervention. Participants were generally healthy and screened for inclusion/exclusion criteria for the parent study. Thirty-eight participants were recruited (Mean age = 65.0 [SD = 5.1]; 60% female) and the final longitudinal sample was 32 participants. Participants provided a passive drool sample at: waking, 15, 30, and 45 min post-waking to assess the cortisol awakening response (CAR) and 3, 6, 9, and 12 h post-waking to assess daily area under the curve for cortisol. Salivary cortisol was quantified by liquid chromatography coupled to tandem mass spectrometry. The exercise intervention increased CAR but no differences were observed in daily AUC. In addition, larger increases in CAR were positively associated with greater decreases in subjective stress. Thus, aerobic exercise improved the CAR in otherwise healthy, but sedentary older adults and greater improvements in CAR were associated with greater reductions in perceived stress.
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http://dx.doi.org/10.1016/j.psyneuen.2019.01.012DOI Listing
May 2019

Vascular responses to hypoxia are not impaired in obstructive sleep apnoea patients free of overt cardiovascular disease.

Exp Physiol 2019 04 27;104(4):580-600. Epub 2019 Feb 27.

Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

New Findings: What is the central question of this study? Does treatment of obstructive sleep apnoea (OSA) with nocturnal oxygen or continuous positive airway pressure (CPAP) improve hypoxic vascular responses, which are reportedly impaired in OSA? What is the main finding and its importance? Cerebrovascular and cardiovascular hypoxic responses were not impaired in OSA patients free of overt cardiovascular disease and known risk factors, and were not altered by nocturnal oxygen or CPAP treatment. We conclude that this OSA patient phenotype has normal vascular responses to hypoxia and is unlikely to obtain long term cardiovascular benefits from nocturnal oxygen or CPAP therapy.

Abstract: Cerebral blood flow (CBF) and cardiovascular responses to hypoxia are reportedly impaired in obstructive sleep apnoea (OSA) patients and corrected by continuous positive airway pressure (CPAP), beneficial effects that are ascribed to correction of OSA-related intermittent hypoxia (IH). However, CPAP corrects both IH and ancillary OSA features (i.e. intermittent hypercapnia, sympathetic activation, blood pressure surges, negative intrathoracic pressure swings and sleep fragmentation). Whether correction of these ancillary OSA features contribute to CPAP's beneficial effects on vascular hypoxic responses is unknown. Nocturnal oxygen corrects OSA-induced IH, but apnoeas and ancillary features persist. Thus, we examined the effects of nocturnal oxygen and CPAP on cerebrovascular and cardiovascular hypoxic responses in untreated OSA patients. Responses were assessed in 52 OSA patients free of overt cardiovascular disease and known risk factors at baseline, after 2 weeks of nocturnal oxygen (n = 26) or no treatment (n = 26), and after ∼4 weeks of CPAP treatment (n = 40). Twenty-two age-matched controls were assessed at baseline and follow-up visits. Resting, isocapnic euoxia mean blood pressure was decreased following nocturnal oxygen (-3.6 ± 6.0 mmHg; P = 0.006) and CPAP (-4.5 ± 7.5 mmHg; P < 0.001) while cerebrovascular conductance was increased with CPAP (P = 0.001). However, these changes were not different from controls. Unexpectedly, OSA patients and controls had similar hypoxic vascular responses at baseline that were not changed by either nocturnal oxygen or CPAP. We conclude that OSA patients free of overt cardiovascular disease and known risk factors did not have impaired cerebrovascular or cardiovascular responses to hypoxia and are unlikely to obtain long term cardiovascular benefits from nocturnal oxygen or CPAP therapy.
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http://dx.doi.org/10.1113/EP086845DOI Listing
April 2019

Novel Approach to Characterize Heterogeneity in an Aerobic Exercise Intervention.

Med Sci Sports Exerc 2019 07;51(7):1506-1516

Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CANADA.

Purpose: Exercise intervention studies for brain health can be difficult to interpret due to heterogeneity in exercise intensity, exercise duration, and in adherence to the exercise intervention. This study aimed to characterize heterogeneity in these components in a cohort of healthy middle-age and older adults who participated in a prescribed 6-month supervised aerobic exercise intervention as part of the Brain in Motion study.

Methods And Results: Group-based multitrajectory analysis (GBMTA) was used to characterize variation in the trajectory of exercise intensity and duration for male and female participants in the first 3 months of the exercise program. The GBMTA for males and females revealed two distinct trajectory subgroups, namely, "high-increasing" (HI) and "low-increasing" (LI). Logistic regression was used to assess the association between the identified latent subgroups and (i) demographic characteristics; (ii) physiological characteristics, including cardiovascular and cerebrovascular function; (iii) genetic characteristics; and (iv) adherence with American College of Sports Medicine guidelines on exercise for older adults. Of the 196 participants, 54.1% met the American College of Sports Medicine aerobic exercise targets for intensity and duration during the intervention. Aerobic fitness (maximal oxygen uptake; odds ratio, 1.27; P < 0.01) was significantly different between these trajectory subgroups in males, and cerebrovascular function (cerebrovascular resistance; odds ratio, 0.14; P < 0.01) was significantly different between these trajectory subgroups in females.

Conclusion: This novel approach to tracking a prespecified exercise program highlights that there are individual and group-specific variations within a prescribed exercise intervention. Characterizing exercise adherence in this way holds promise in developing optimized exercise prescriptions tailored to individual baseline characteristics, and additionally highlighting those participants at greatest risk of not meeting minimum dosage requirements for physiological and/or cognitive health.
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http://dx.doi.org/10.1249/MSS.0000000000001909DOI Listing
July 2019

Effects of Six-Month Aerobic Exercise Intervention on Sleep in Healthy Older Adults in the Study: A Pilot Study.

J Alzheimers Dis Rep 2018 Dec 24;2(1):229-238. Epub 2018 Dec 24.

Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Background: Sleep disturbances have been shown to be associated with the presence of the apolipoprotein () 4 allele, the well-known genetic risk factor for late-onset sporadic Alzheimer's disease (AD).

Objective: This study quantifies the effects of a six-month aerobic exercise intervention on objective and subjective sleep quality in middle-aged to older individuals including those at increased genetic risk for late-onset sporadic Alzheimer's disease (AD), who carry the apolipoprotein () 4 risk allele.

Methods: 199 sedentary men and women without significant cognitive impairments were enrolled in the study, a quasi-experimental single group pre-test/post-test study with no control group. Participants completed a six-month aerobic exercise intervention and consented to genetic testing. Genotyping of confirmed that 54 individuals were carriers of the 4 allele. Participants' subjective quality of sleep was assessed with the Pittsburgh Sleep Quality Index (PSQI) pre- and post-intervention. A convenience sample of participants ( = 29, 4+ = 7) consented to undergo two nights of in-home polysomnography (PSG) pre- and post intervention. Sleep architecture and respiratory variables were assessed.

Results: The six-month aerobic exercise intervention significantly improved participants' total PSQI score, sleep efficiency, and sleep latency in the full sample ( = 199). PSG results showed that total sleep time and sleep onset latency significantly improved over the course of the exercise intervention only in individuals who carried the 4 allele. These results are, however, exploratory and need to be carefully interpreted due to the rather small number of 4+ in the PSG subgroup.

Conclusions: The six-month aerobic exercise intervention significantly improved participants' sleep quality with beneficial effects on PSG shown in individuals at increased genetic risk for late-onset sporadic AD.
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http://dx.doi.org/10.3233/ADR-180079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311349PMC
December 2018

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

Front Physiol 2018 21;9:1131. Epub 2018 Aug 21.

Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

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.
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http://dx.doi.org/10.3389/fphys.2018.01131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111975PMC
August 2018

CPAP Therapy Delays Cardiovagal Reactivation and Decreases Arterial Renin-Angiotensin System Activity in Humans With Obstructive Sleep Apnea.

J Clin Sleep Med 2018 09 15;14(9):1509-1520. Epub 2018 Sep 15.

Department of Medicine, University of Calgary, Calgary, Alberta, Canada.

Study Objectives: Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk. The effect of OSA treatment with continuous positive airway pressure (CPAP) on the cardiovascular response to a stressor is unknown. We sought to determine the effect of CPAP therapy on heart rate variability (HRV) and arterial stiffness, at baseline, in response to, and recovery from a physiological stressor, Angiotensin II (AngII), in humans with OSA.

Methods: Twenty-five incident healthy subjects (32% female; 49 ± 2 years) with moderate-severe OSA and nocturnal hypoxia were studied in high-salt balance, a state of maximal renin-angiotensin system (RAS) suppression, before CPAP, and after 4 weeks of effective CPAP therapy (usage > 4 h/night) in a second identical study day. HRV was calculated by spectral power and time domain analysis. Aortic augmentation index (AIx) and carotid-femoral pulse-wave velocity (PWV) were measured by applanation tonometry. HRV and arterial stiffness were measured at baseline and in response to AngII challenge (3 ng/ kg/min·30 minutes, 6 ng/kg/min·30 minutes, recovery·30 minutes). The primary outcome was the association between CPAP treatment and HRV and arterial stiffness responses to, and recovery from, AngII challenge. In an exploratory analysis subjects were stratified by sex.

Results: CPAP corrected OSA and nocturnal hypoxemia. CPAP treatment was associated with increased sensitivity and delayed recovery from AngII (Δln HF [high frequency; recovery: -0.09 ± 0.19 versus -0.59 ± 0.17 ms, = .042; ΔrMSSD [root mean successive differences; recovery: -0.4 ± 2.0 versus -7.2 ± 1.9 ms, = .001], ΔpNN50 [percentage of normal waves differing ≥ 50 ms compared to the preceding wave; AngII: 1.3 ± 2.3 versus -3.0 ± 2.4%, = .043; recovery: -0.4 ± 1.4 versus -6.0 ± 1.9%, = .001], all values pre-CPAP versus post-CPAP treatment). No differences were observed by sex. There was increased AIx sensitivity to AngII after CPAP among men (8.2 ± 1.7 versus 11.9 ± 2.2%, = .046), but not women (11.4 ± 1.5 versus 11.6 ± 2.1%, = .4). No change in PWV sensitivity was observed in either sex.

Conclusions: CPAP therapy was associated with delayed cardiovagal reactivation after a stressor and down-regulation of the arterial RAS. These findings may have important implications in mitigating cardiovascular risk in both men and women with OSA.
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http://dx.doi.org/10.5664/jcsm.7326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134233PMC
September 2018

Determining optimal poststroke exercise: Study protocol for a randomized controlled trial investigating therapeutic intensity and dose on functional recovery during stroke inpatient rehabilitation.

Int J Stroke 2019 01 16;14(1):80-86. Epub 2018 Jul 16.

2 Rehabilitation Research Program, Vancouver Coastal Health Research Institute, Vancouver, Canada.

Rationale: A top priority in stroke rehabilitation research is determining the appropriate exercise dose to optimize recovery. Although more intensive rehabilitation very early after stroke may be deleterious to recovery, inpatient rehabilitation, occurring after acute care, may be a more appropriate setting to assess therapeutic dose on neurological recovery.

Hypothesis: Individuals receiving higher intensity and dose exercise programs will yield greater improvements in walking ability over usual inpatient physical therapy care.

Methods And Design: Seventy-five individuals across seven inpatient rehabilitation sites in Canada will be randomized into one of three treatment programs, each 5 days/week, for four weeks and monitored for exertion (heart rate) and repetitions (step count).

Study Outcomes: The primary outcome measure is the 6 min walk and secondary outcomes include functional independence, cognitive, and quality-of-life measures. Outcome data will be assessed at four time points.

Summary: This trial will contribute to our knowledge of the therapeutic intensity and dose necessary to maximize functional recovery at a very important stage of rehabilitation and neural recovery poststroke.
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http://dx.doi.org/10.1177/1747493018785064DOI Listing
January 2019

Protective Effects of Exercise on Cognition and Brain Health in Older Adults.

Exerc Sport Sci Rev 2018 10;46(4):215-223

Department of Physiology & Pharmacology.

Accelerated trajectories of cognitive decline in older adults may increase the risk of developing Alzheimer disease and related dementias (ADRD). Physical activity has potential modifying effects on these changes that could prevent or delay ADRD. This review explores the hypothesis that multiple, mutually complimentary, and interacting factors explain the positive association between exercise and the optimization of cognition in older adults.
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http://dx.doi.org/10.1249/JES.0000000000000161DOI Listing
October 2018

Cognition and mobility show a global association in middle- and late-adulthood: Analyses from the Canadian Longitudinal Study on Aging.

Gait Posture 2018 07 19;64:238-243. Epub 2018 Jun 19.

Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Human Brain Activity, Department of Psychiatry, University of Oxford, Oxford, United Kingdom; Global Brain Health Institute, Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA. Electronic address:

Background: Given our aging population, there's great interest in identifying modifiable risk factors for cognitive decline. Studies have highlighted the relationship between aspects of mobility and cognitive processes. However, cognition and mobility are both multifaceted concepts and their interrelationships remain to be well defined.

Research Question: Here, we firstly aimed to replicate cross-sectional associations between objective measures of mobility and cognition. Second, we tested whether these associations remained after the consideration of multiple age-related confounders. Finally, to test the hypothesis that the association between mobility and cognition is stronger in older adults, we examined the moderating effect of age in the association between mobility and cognition.

Methods: In the Canadian Longitudinal Study on Aging, 28,808 community-dwelling adults (aged 45-87; 51% female) completed mobility (gait, balance and chair stands) and cognitive (memory, executive function and processing speed) assessments. General linear models were used to examine mobility-cognition relationships and the moderating effect of age.

Results: Cognitive measures were significantly associated with mobility measures (all p < 0.001). Further, age significantly moderated the mobility-cognition relationship, with the strength of the associations generally increasing with age.

Significance: All cognitive measures were related to indices of mobility, suggesting a global association. In our moderation analyses, the mobility-cognition relationship often increased with age. However, the small effect sizes observed suggest that mobility is, in isolation, not a strong correlate of cognitive performance in middle and late-adulthood.
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http://dx.doi.org/10.1016/j.gaitpost.2018.06.116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052573PMC
July 2018

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

Front Physiol 2018 4;9:677. Epub 2018 Jun 4.

Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

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. 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. In , PVT-RS was slower at HA1 compared to LA (4.1 ± 0.8 vs. 4.5 ± 0.6 s, respectively, = 0.029), but not at HA6 (4.6 ± 0.7; > 0.05). In , PVT-RS at HA1 (4.6 ± 0.7) and HA6 (4.8 ± 0.6) were not different from LA (4.8 ± 0.6, > 0.05) and significantly greater than corresponding values in . In both cycles, AMS scores were higher at HA1 than at LA and HA6 ( < 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 and they were significantly reduced during acclimatization exposures (LA vs. 1st night, > 0.05; LA vs. 5th night, = 0.012; and 1st vs. 5th night, = 0.054). LA, 1st and 5th nights TST in were 477.5 ± 96.9, 430.9 ± 34, and 341.4 ± 32.2, respectively, and we observed similar deteriorations in TST as in (LA vs. 1st night, > 0.05; LA vs. 5th night, = 0.001; and 1st vs. 5th night, < 0.0001). At HA1, subjects who reported higher AMS-C scores exhibited slower PVT-RS ( = -0.56; < 0.01). Subjects with higher AMS-C scores took longer time to react to the stimuli during acute exposure ( = 0.62, < 0.01) during HA1 of . 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.
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http://dx.doi.org/10.3389/fphys.2018.00677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994420PMC
June 2018

Exercise Performance of Lowlanders with COPD at 2,590 m: Data from a Randomized Trial.

Respiration 2018;95(6):422-432. Epub 2018 Mar 2.

Department of Respiratory Medicine, University Hospital Zurich, Zurich, Switzerland.

Background: Effects of hypobaric hypoxia at altitude on exercise performance of lowlanders with chronic obstructive pulmonary disease (COPD) have not been studied in detail.

Objectives: To quantify changes in exercise performance and associated physiologic responses in lowlanders with COPD travelling to moderate altitude.

Methods: A total of 31 COPD patients with a median age (quartiles) of 66 years (59; 69) and FEV1 of 56% predicted (49; 69) living below 800 m performed a constant-load bicycle exercise to exhaustion at 60% of the maximal work rate at 490 m (Zurich) and at an identical work rate at 2,590 m (Davos) in randomized order. Pulmonary gas exchange, pulse oximetry (SpO2), cerebral tissue oxygenation (CTO; near-infrared spectroscopy), and middle cerebral artery peak blood flow velocity (MCAv) by Doppler ultrasound during 30 s at end exercise were compared between altitudes.

Results: With ascent from 490 to 2,590 m, the median endurance time (quartiles) was reduced from 500 s (256; 795) to 205 s (139; 297) by a median (95% CI) of 303 s (150-420) (p < 0.001). End exercise SpO2 decreased from 92% (89; 94) to 81% (77; 84) and CTO from 62% (56; 66) to 55% (50; 60); end exercise minute ventilation increased from 40.6 L/min (35.5; 47.8) to 47.2 L/min (39.6; 58.7) (p < 0.05; all comparisons 2,590 vs. 490 m). MCAv increased similarly from rest to end exercise at 490 m (+25% [17; 36]) and at 2,590 m (+21% [14; 30]). However, the ratio of MCAv increase to SpO2 drop during exercise decreased from +6%/% (3; 12) at 490 m to +3%/% (2; 5) at 2,590 m (p < 0.05).

Conclusions: In lowlanders with COPD travelling to 2,590 m, exercise endurance is reduced by more than half compared to 490 m in association with reductions in systemic and cerebral oxygen availability.
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http://dx.doi.org/10.1159/000486450DOI Listing
November 2018

Plasma Exosomes and Improvements in Endothelial Function by Angiotensin 2 Type 1 Receptor or Cyclooxygenase 2 Blockade following Intermittent Hypoxia.

Front Neurol 2017 22;8:709. Epub 2017 Dec 22.

Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, University of Chicago, Chicago, IL, United States.

Intermittent hypoxia (IH) is associated with increased endothelial dysfunction and cardiovascular disorders. Exosomes released in biological fluids may act as vehicles for propagating such damage, modifying the functional phenotype of endothelial cells. Drug interventions, however, may provide protection for the endothelium, in spite of exosomal activity. Using an experimental human model of IH, we investigated whether the beneficial effects of two drugs, celecoxib (CEL) and losartan (LOS), on IH-induced vascular dysfunction was mediated exosomes or independent of IH-induced exosomal cargo alterations. We hypothesized that the beneficial effects of CEL and LOS on IH-induced vascular dysfunction would be mediated modifications of exosomal properties by the drugs, rather than by direct effects of the drugs on the endothelium. Ten male volunteers were exposed to IH (single exposure of 6 h) while receiving LOS, CEL, or placebo (P) for 4 days before IH exposures, and plasma samples were obtained from which exosomes were isolated, and incubated with naïve human endothelial cell cultures either not treated or pretreated with LOS, CEL, or P. Functional reporter assays (monolayer impedance, monocyte adhesion, and eNOS phosphorylation) revealed that the degree of exosome-induced endothelial dysfunction was similar among IH-exposed subjects independent of drug treatment. However, pretreatment of naïve endothelial cells with LOS or CEL before addition of exosomes from IH-exposed subjects afforded significant protection. Thus, the cardiovascular protective impact of LOS and CEL appears to be mediated by their direct effects on endothelial cells, rather than modulation of exosomal cargo.
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http://dx.doi.org/10.3389/fneur.2017.00709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743928PMC
December 2017

Human cerebral blood flow control during hypoxia: focus on chronic pulmonary obstructive disease and obstructive sleep apnea.

J Appl Physiol (1985) 2017 Nov 10;123(5):1350-1361. Epub 2017 Aug 10.

Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada;

The brain is a vital organ that relies on a constant and adequate blood flow to match oxygen and glucose delivery with the local metabolic demands of active neurons. Thus exquisite regulation of cerebral blood flow (CBF) is particularly important under hypoxic conditions to prevent a detrimental decrease in the partial pressure of oxygen within the brain tissues. Cerebrovascular sensitivity to hypoxia, assessed as the change in CBF during a hypoxic challenge, represents the capacity of cerebral vessels to respond to, and compensate for, a reduced oxygen supply, and has been shown to be impaired or blunted in a number of conditions. For instance, this is observed with aging, and in clinical conditions such as untreated obstructive sleep apnea (OSA) and in healthy humans exposed to intermittent hypoxia. This review will ) provide a brief overview of cerebral blood flow regulation and results of pharmacological intervention studies which we have performed to better elucidate the basic mechanisms of cerebrovascular regulation in humans; and ) present data from studies in clinical and healthy populations, using a translational physiology approach, to investigate human CBF control during hypoxia. Results from studies in patients with chronic obstructive pulmonary disease and OSA will be presented to identify the effects of the disease processes on cerebrovascular sensitivity to hypoxia. Data emerging from experimental human models of intermittent hypoxia during wakefulness will also be reviewed to highlight the effects of intermittent hypoxia on the brain.
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http://dx.doi.org/10.1152/japplphysiol.00352.2017DOI Listing
November 2017

Association between glycemic load and cognitive function in community-dwelling older adults: Results from the Brain in Motion study.

Clin Nutr 2018 10 17;37(5):1690-1699. Epub 2017 Jul 17.

Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada. Electronic address:

Background: Impaired glucose tolerance is a risk factor for non-age-related cognitive decline and is also associated with measures of physical activity (PA) and cardiorespiratory fitness (CRF). A low glycemic load (GL) diet can aid in the management of blood glucose levels, but little is known about its effect on cognition with poor glucoregulation.

Objective: We assessed the relation between GL and cognitive function by glucoregulation and possible mediatory effects by CRF and PA in older adults from the Brain in Motion Study.

Design: A cross-sectional analysis of 194 cognitively healthy adults aged ≥55 years (mean = 65.7, SD = 6.1) was conducted. GL was assessed using a quantitative food frequency questionnaire, and glucoregulation was characterized on the HOMA-IR index. Subjects also completed a cognitive assessment, CRF testing, a validated self-reported PA questionnaire, and a blood draw. Multiple linear regression models adjusted for significant covariates were used to evaluate the relation between GL and cognition, and mediation by CRF and PA was also assessed.

Results: GL was inversely associated with global cognition (β = -0.014; 95% CI -0.024, -0.004) and figural memory (β = -0.035; 95% CI -0.052, -0.018) in subjects with poor glucoregulation. Neither CRF nor PA mediated these relations. In subjects with good glucoregulation, no association was found between GL and cognitive function (p > 0.05).

Conclusions: A low GL diet is associated with better cognitive function in older adults with poor glucoregulation. This study provides supportive evidence for the role of GL in maintaining better cognitive function during the aging process.
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http://dx.doi.org/10.1016/j.clnu.2017.07.011DOI Listing
October 2018

Impact of obstructive sleep apnoea and intermittent hypoxia on cardiovascular and cerebrovascular regulation.

Exp Physiol 2017 07 27;102(7):743-763. Epub 2017 Jun 27.

Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

New Findings: What is the topic of this review? This review examines the notion that obstructive sleep apnoea (OSA) and intermittent hypoxia (IH) have hormetic effects on vascular health. What advances does it highlight? Clinical (OSA patient) and experimental animal and human models report that IH is detrimental to vascular regulation. However, mild IH and, by extension, mild OSA also have physiological and clinical benefits. This review highlights clinical and experimental animal and human data linking OSA and IH to vascular disease and discusses how hormetic effects of OSA and IH relate to OSA severity, IH intensity and duration, and patient/subject age. Obstructive sleep apnoea (OSA) is associated with increased risk of cardiovascular and cerebrovascular disease, a consequence attributed in part to chronic intermittent hypoxia (IH) resulting from repetitive apnoeas during sleep. Although findings from experimental animal, and human, models have shown that IH is detrimental to vascular regulation, the severity of IH used in many of these animal studies [e.g. inspired fraction of oxygen (FI,O2) = 2-3%; oxygen desaturation index = 120 events h ] is considerably greater than that observed in the majority of patients with OSA. This may also explain disparities between animal and recently developed human models of IH, where IH severity is, by necessity, less severe (e.g. FI,O2 = 10-12%; oxygen desaturation index = 15-30 events h ). In this review, we highlight the current knowledge regarding the impact of OSA and IH on cardiovascular and cerebrovascular regulation. In addition, we critically discuss the recent notion that OSA and IH may have hormetic effects on vascular health depending on conditions such as OSA severity, IH intensity and duration, and age. In general, data support an independent causal link between OSA and vascular disease, particularly for patients with severe OSA. However, the data are equivocal for older OSA patients and patients with mild OSA, because advanced age and short-duration, low-intensity IH have been reported to provide a degree of protection against IH and ischaemic events such as myocardial infarction and stroke, respectively. Overall, additional studies are needed to investigate the beneficial/detrimental effects of mild OSA on the various vascular beds.
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http://dx.doi.org/10.1113/EP086051DOI Listing
July 2017

Cyclooxygenase-2 Inhibition Limits Angiotensin II-Induced DNA Oxidation and Protein Nitration in Humans.

Front Physiol 2017 10;8:138. Epub 2017 Mar 10.

Faculty of Medicine, Libin Cardiovascular Institute of Alberta, University of CalgaryCalgary, AB, Canada; Department of Medicine, Faculty of Medicine, University of CalgaryCalgary, AB, Canada.

Compared to other cyclooxygenase-2 inhibitors, celecoxib is associated with a lower cardiovascular risk, though the mechanism remains unclear. Angiotensin II is an important mediator of oxidative stress in the pathophysiology of vascular disease. Cyclooxygenase-2 may modify the effects of angiotensin II though this has never been studied in humans. The purpose of the study was to test the effects of selective cyclooxygenase-2 inhibition on plasma measures of oxidative stress, the vasoconstrictor endothelin-1, and nitric oxide metabolites, both at baseline and in respose to Angiotensin II challenge in healthy humans. Measures of 8-hydroxydeoxyguanosine, advanced oxidation protein products, nitrotyrosine, endothelin-1, and nitric oxide metabolites were assessed from plasma samples drawn at baseline and in response to graded angiotensin II infusion (3 ng/kg/min × 30 min, 6 ng/kg/min × 30 min) before and after 14 days of cyclooxygenase-2 inhibition in 14 healthy subjects (eight male, six female) in high salt balance, a state of maximal renin angiotensin system suppression. Angiotensin II infusion significantly increased plasma oxidative stress compared to baseline (8-hydroxydeoxyguanosine; +17%; advanced oxidation protein products; +16%), nitrotyrosine (+76%). Furthermore, levels of endothelin-1 levels were significantly increased (+115%) and nitric oxide metabolites were significantly decreased (-20%). Cycloxygenase-2 inhibition significantly limited the increase in 8-hydroxydeoxyguanosine, nitrotyrosine and the decrease in nitric oxide metabolites induced by angiotensin II infusion, though no changes in advanced oxidation protein products and endothelin-1 concentrations were observed. Cyclooxygenase-2 inhibition with celecoxib partially limited the angiotensin II-mediated increases in markers of oxidative stress in humans, offering a potential physiological pathway for the improved cardiovascular risk profile of this drug.
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http://dx.doi.org/10.3389/fphys.2017.00138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344903PMC
March 2017

Medication use by middle-aged and older participants of an exercise study: results from the Brain in Motion study.

BMC Complement Altern Med 2017 Feb 10;17(1):105. Epub 2017 Feb 10.

Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, HMRB-210, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada.

Background: Over the past 50 years, there has been an increase in the utilization of prescribed, over-the-counter (OTC) medications, and natural health products. Although it is known that medication use is common among older persons, accurate data on the patterns of use, including the quantity and type of medications consumed in a generally healthy older population from a Canadian perspective are lacking. In this study, we study the pattern of medication use in a sedentary but otherwise healthy older persons use and determined if there was an association between medication use and aerobic fitness level.

Methods: All participants enrolled in the Brain in Motion study provided the name, formulation, dosage and frequency of any medications they were consuming at the time of their baseline assessment. Maximal aerobic capacity (VOmax) was determined on each participant.

Results: Two hundred seventy one participants (mean age 65.9 ± 6.5 years; range 55-92; 54.6% females) were enrolled. Most were taking one or more (1+) prescribed medication (n = 204, 75.3%), 1+ natural health product (n = 221, 81.5%) and/or 1+ over-the-counter (OTC) drug (n = 174, 64.2%). The most commonly used prescribed medications were HMG-CoA reductase inhibitors (statins) (n = 52, 19.2%). The most common natural health product was vitamin D (n = 201, 74.2%). For OTC drugs, non-steroidal anti-inflammatories (n = 82, 30.3%) were the most common. Females were more likely than males to take 1+ OTC medications, as well as supplements. Those over 65 years of age were more likely to consume prescription drugs than their counterparts (p ≤ 0.05). Subjects taking more than two prescribed or OTC medications were less physically fit as determined by their VOmax. The average daily Vitamin D intake was 1896.3 IU per participant.

Conclusions: Medication use was common in otherwise healthy older individuals. Consumption was higher among females and those older than 65 years. Vitamin D intake was over two-fold higher than the recommended 800 IU/day for older persons, but within the tolerable upper intake of 4,000 IU/day. The appropriateness of the high rate of medication use in this generally healthy population deserves further investigation.
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http://dx.doi.org/10.1186/s12906-017-1595-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303244PMC
February 2017

Effects of exercise on markers of oxidative stress: an Ancillary analysis of the Alberta Physical Activity and Breast Cancer Prevention Trial.

BMJ Open Sport Exerc Med 2016 24;2(1):e000171. Epub 2016 Oct 24.

Faculty of Physical Education and Recreation , University of Alberta , Edmonton, Alberta , Canada.

Background: Oxidative stress may contribute to cancer aetiology through several mechanisms involving damage to DNA, proteins and lipids leading to genetic mutations and genomic instability. The objective of this study was to determine the effects of aerobic exercise on markers of oxidative damage and antioxidant enzymes in postmenopausal women.

Methods: The Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA) was a two-centre, two-armed randomised trial of 320 inactive, healthy, postmenopausal women aged 50-74 years. Participants were randomly assigned to a year-long exercise intervention (225 min/week) or a control group while being asked to maintain a normal diet. Fasting blood samples were obtained and plasma concentrations of two oxidative damage markers (8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostaglandin F2α (8-Iso-PGF2α)) and two antioxidant enzymes (superoxide dismutase and catalase) were measured at baseline, 6 months and 12 months. Intention-to-treat (ITT) and per-protocol analyses were performed using linear mixed models adjusted for baseline biomarker concentrations. A further exercise adherence analysis, based on mean minutes of exercise per week, was also performed.

Results: In the ITT and per-protocol analyses, the exercise intervention did not have any statistically significant effect on either oxidative damage biomarkers or antioxidant enzyme activity.

Conclusions: A year-long aerobic exercise intervention did not have a significant impact on oxidative stress in healthy, postmenopausal women.

Trial Registration Number: NCT00522262.
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http://dx.doi.org/10.1136/bmjsem-2016-000171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125419PMC
October 2016

Evidence of association between sleep quality and APOE ε4 in healthy older adults: A pilot study.

Neurology 2016 Oct;87(17):1836-1842

From the Department of Physiology & Pharmacology (L.L.D., A.V.T., A.N., K.D.G., G.E., M.J.P.), Hotchkiss Brain Institute (L.L.D., S.J.G., A.V.T., A.N., K.D.G., P.J.H., M.J.P.), Department of Medical Sciences (S.J.G.), Department of Medicine (J.K.R., P.J.H.), Department of Medical Genetics (J.S.P.), Department of Clinical Neurosciences (M.J.P.), and Libin Cardiovascular Institute of Alberta (M.J.P.), Cumming School of Medicine, and Alberta Children's Hospital Research Institute for Child and Maternal Health (J.S.P.), Faculty of Kinesiology (M.J.P.), and Sleep Centre, Foothills Medical Centre (J.K.R., P.J.H.), University of Calgary; and Department of Psychiatry, Faculty of Medicine (G.E.), and Department of Psychology and Neuroscience, Faculty of Science (G.E.), Dalhousie University, Halifax, Canada.

Background: It has been estimated that the prevalence of Alzheimer disease (AD) and related dementias will triple by 2035, unless effective interventions or treatments are found for the neurodegenerative disease. Understanding sleep changes as a marker for both AD risk and progression is a burgeoning area of investigation. Specifically, there is emerging evidence that both sleep disturbances and the APOE ε4 allele are associated with increased dementia risk. Previous research has suggested that in AD, individuals carrying the APOE ε4 allele have decreased sleep quality compared to individuals without the APOE ε4 allele. This observational trial aimed to determine if healthy older adults with the risk allele (APOE ε4+) have more sleep complaints or evidence of objective sleep disruption compared to healthy older adults without the risk allele (APOE ε4-).

Methods: Within the larger Brain in Motion study, a subset of participants completed at-home polysomnography (PSG) and actigraphy sleep assessment. Subjective sleep complaints were determined using the Pittsburgh Sleep Quality Index.

Results: This investigation found a significant relationship between presence of APOE ε4 allele and objective sleep disturbances measured by both actigraphy and PSG, but not subjective sleep complaints in a healthy population screened for dementia.

Conclusions: These data suggest that the influence of APOE ε4 allele on objective sleep quality may precede subjective sleep complaints in individuals at increased risk for dementia.
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http://dx.doi.org/10.1212/WNL.0000000000003255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5089524PMC
October 2016

Increased ventilatory response to carbon dioxide in COPD patients following vitamin C administration.

ERJ Open Res 2015 May 15;1(1). Epub 2015 Sep 15.

Dept of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada; Dept of Clinical Neuroscience, University of Calgary, Calgary, AB, Canada; Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.

Patients with chronic obstructive pulmonary disease (COPD) have decreased ventilatory and cerebrovascular responses to hypercapnia. Antioxidants increase the ventilatory response to hypercapnia in healthy humans. Cerebral blood flow is an important determinant of carbon dioxide/hydrogen ion concentration at the central chemoreceptors and may be affected by antioxidants. It is unknown whether antioxidants can improve the ventilatory and cerebral blood flow response in individuals in whom these are diminished. Thus, we aimed to determine the effect of vitamin C administration on the ventilatory and cerebrovascular responses to hypercapnia during healthy ageing and in COPD. Using transcranial Doppler ultrasound, we measured the ventilatory and cerebral blood flow responses to hyperoxic hypercapnia before and after an intravenous vitamin C infusion in healthy young () and older () subjects and in moderate COPD. Vitamin C increased the ventilatory response in COPD patients (mean (95% CI) 1.1 (0.9-1.1) 1.5 (1.1-2.0) L·min·mmHg, p<0.05) but not in (2.5 (1.9-3.1) 2.4 (1.9-2.9) L·min·mmHg, p>0.05) or (1.3 (1.0-1.7) 1.3 (1.0-1.7) L·min·mmHg, p>0.05) healthy subjects. Vitamin C did not affect the cerebral blood flow response in the young or older healthy subjects or COPD subjects (p>0.05). Vitamin C increases the ventilatory but not cerebrovascular response to hyperoxic hypercapnia in patients with moderate COPD.
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http://dx.doi.org/10.1183/23120541.00017-2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005137PMC
May 2015

Effects of continuous positive airway pressure and isocapnic-hypoxia on cerebral autoregulation in patients with obstructive sleep apnoea.

J Physiol 2016 12;594(23):7089-7104

Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Key Points: Altered cerebral autoregulation (CA) in obstructive sleep apnoea (OSA) patients may contribute to increased stroke risk in this population; the gold standard treatment for OSA is continuous positive airway pressure, which improves cerebrovascular regulation and may decrease the risk of stroke. Isocapnic-hypoxia impairs CA in healthy subjects, but it remains unknown in OSA whether impaired CA is further exacerbated by isocapnic-hypoxia and whether it is improved by treatment with continuous positive airway pressure. During normoxia, CA was altered in the more severe but not in the less severe OSA patients, while, in contrast, during isocapnic-hypoxia, CA was similar between groups and tended to improve in patients with more severe OSA compared to normoxia. From a clinical perspective, one month of continuous positive airway pressure treatment does not improve CA. From a physiological perspective, this study suggests that sympathetic overactivity may be responsible for altered CA in the more severe OSA patients.

Abstract: Cerebral autoregulation (CA) impairment may contribute to the increased risk of stroke associated with obstructive sleep apnoea (OSA). It is unknown if impaired CA is further exacerbated by isocapnic-hypoxia and whether it is improved by treatment of OSA with continuous positive airway pressure (CPAP). CA was assessed during wakefulness in 53 OSA patients (50.3 ± 9.3 years) and 21 controls (49.8 ± 8.6 years) at baseline and following a minimum of 1 month of effective CPAP therapy (OSA patients, n = 40). Control participants (n = 21) performed a follow-up visit to control for time effects within OSA patients between baseline and the post-CPAP visit. Beat-by-beat middle cerebral artery blood flow velocity and mean arterial blood pressure (MBP), and breath-by-breath end-tidal partial pressure of CO (P ET ,CO2) were monitored. CA was determined during normoxia and isocapnic-hypoxia using transfer function (phase and gain) and coherence analysis (including multiple and partial coherence (using MBP and P ET ,CO2 as inputs)) in the very low frequency range (0.03-0.07 Hz). OSA patients were divided into two subgroups (less severe and more severe) based upon the median respiratory disturbance index (RDI). During normoxia, the more severe OSA patients (RDI 45.9 ± 10.3) exhibited altered CA compared to controls and the less severe OSA patients (RDI 24.5 ± 5.9). In contrast, during isocapnic-hypoxia, CA was similar between groups. CPAP had no effect on CA. In conclusion, CA is altered in the more severe OSA patients during normoxia but not during isocapnic-hypoxia and CPAP treatment does not impact CA.
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http://dx.doi.org/10.1113/JP272967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5134415PMC
December 2016

Effect on Intermittent Hypoxia on Plasma Exosomal Micro RNA Signature and Endothelial Function in Healthy Adults.

Sleep 2016 Dec 1;39(12):2077-2090. Epub 2016 Dec 1.

Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Science Division, University of Chicago, Chicago, IL.

Study Objective: Intermittent hypoxia (IH) is associated with increased risk of cardiovascular disease. Exosomes are secreted by most cell types and released in biological fluids, including plasma, and play a role in modifying the functional phenotype of target cells. Using an experimental human model of IH, we investigated potential exosome-derived biomarkers of IH-induced vascular dysfunction.

Methods: Ten male volunteers were exposed to room air (D0), IH (6 h/day) for 4 days (D4) and allowed to recover for 4 days (D8). Circulating plasma exosomes were isolated and incubated with human endothelial monolayer cultures for impedance measurements and RNA extracted and processed with messenger RNA (mRNA) arrays to identify gene targets. In addition, immunofluorescent assessments of endothelial nitric oxide synthase () mRNA expression, ICAM-1 cellular distribution were conducted.

Results: Plasma exosomal micro RNAs (miRNAs) were profiled. D4 exosomes, primarily from endothelial sources, disrupted impedance levels compared to D0 and D8. ICAM-1 expression was markedly upregulated in endothelial cells exposed to D4 exosomes along with significant reductions in expression. Microarray approaches identified a restricted and further validated signature of exosomal miRNAs in D4 exosomes, and mRNA arrays revealed putative endothelial gene target pathways.

Conclusions: In humans, intermittent hypoxia alters exosome cargo in the circulation which promotes increased permeability and dysfunction of endothelial cells . A select number of circulating exosomal miRNAs may play important roles in the cardiovascular dysfunction associated with OSA by targeting specific effector pathways.
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http://dx.doi.org/10.5665/sleep.6302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103796PMC
December 2016

Promoting brain health through exercise and diet in older adults: a physiological perspective.

J Physiol 2016 08 6;594(16):4485-98. Epub 2016 Jan 6.

Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

The rise in incidence of age-related cognitive impairment is a global health concern. Ageing is associated with a number of changes in the brain that, collectively, contribute to the declines in cognitive function observed in older adults. Structurally, the ageing brain atrophies as white and grey matter volumes decrease. Oxidative stress and inflammation promote endothelial dysfunction thereby hampering cerebral perfusion and thus delivery of energy substrates and nutrients. Further, the development of amyloid plaques and neurofibrillary tangles contributes to neuronal loss. Of interest, there are substantial inter-individual differences in the degree to which these physical and functional changes impact upon cognitive function as we grow older. This review describes how engaging in physical activity and cognitive activities and adhering to a Mediterranean style diet promote 'brain health'. From a physiological perspective, we discuss the effects of these modifiable lifestyle behaviours on the brain, and how some recent human trials are beginning to show some promise as to the effectiveness of lifestyle behaviours in combating cognitive impairment. Moreover, we propose that these lifestyle behaviours, through numerous mechanisms, serve to increase brain, cerebrovascular and cognitive reserve, thereby preserving and enhancing cognitive function for longer.
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http://dx.doi.org/10.1113/JP271270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983622PMC
August 2016