Browsing by Author "Poulin, Marc"
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- ItemOpen AccessAssociation between glycemic load and cognitive function in community-dwelling older adults: results from the Brain in Motion study(2017) Garber, Anna; Poulin, Marc; Friedenreich, Christine; Csizmadi, Ilona; Longman, Richard S.; Sajobi, Tolulope; Shearer, JaneBackground: 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: The aim of this thesis was to assess the relation between GL and cognitive function by glucoregulation, and possible mediatory effects by CRF and PA, in older adults. 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 analysis was used to assess potential mediatory effects by CRF and PA. Results: GL was inversely associated with global cognition (β=-0.014; 95% CI -0.024, -0.0036) 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.
- ItemOpen AccessAssociation Between Lifetime Physical Activity and Cognitive Functioning in Middle-aged and Older Community Dwelling Adults: Results from the Brain in Motion Study(2015-09-30) Gill, Stephanie; Poulin, Marc; Friedenreich, Christine MartheObjective: Is total lifetime physical activity (PA) associated with better cognitive functioning with aging and does cerebrovascular function mediates this association? Methods: 226 community dwelling middle-aged and older adults completed the Lifetime Total PA Questionnaire, underwent neuropsychological and cerebrovascular blood flow testing. Multiple robust linear regressions were used to model the associations between lifetime PA and global cognition. Mediation analysis was used to assess the effect of cerebrovascular measures on the association between lifetime PA and global cognition. Results: Better cognitive performance was associated with higher lifetime PA (p=0.045), recreational PA (p=0.018), vigorous intensity PA (p=0.004), PA between the ages of 0-20 years (p=0.028), and the ages of 21-35 years (p<0.0001). Cerebrovascular measures partially mediated the relation between current fitness and cognition. Conclusion: This study revealed significant associations between higher levels of lifetime PA and better cognitive function. Cerebrovascular function partially mediated the relation between current fitness and global cognition.
- ItemOpen AccessCerebrovascular and Ventilatory Function in Chronic Obstructive Pulmonary Disease(2015-02-03) Hartmann, Sara E.; Poulin, MarcChronic Obstructive Pulmonary Disease (COPD) is a disease primarily affecting the pulmonary system, most commonly resulting from prolonged exposure to cigarette smoke. While systemic respiratory disturbances in COPD are apparent, the chemical regulation within the brainstem and at the carotid bodies is unclear. Furthermore, the role that cerebral blood flow contributes to respiratory disturbances is poorly understood. Recent studies have demonstrated peripheral vascular impairments in COPD, which may have further implications for exercise –hyperemia. Oxidative stress serves as a plausible mechanism leading to vascular impairments, and the overall increased risk of stroke and cardiovascular disease. This collection of studies set out to define the ventilatory and cerebrovascular responses to acute alterations in PCO2 and PO2 in COPD patients, and the relationship to oxidative stress. A secondary focus was to characterize both cerebral and peripheral blood flow during exercise. The thesis begins by investigating the cerebrovascular and ventilatory responses to acute euoxic-hypercapnia in mild-moderate COPD patients, and the relationship between these physiological parameters, and markers systemic of oxidative stress. Second, the cerebrovascular responses during moderate cycling exercise are defined. The final three studies collectively investigate the effect of the antioxidant, vitamin C, on the cerebrovascular and ventilatory responses to acute hyperoxic-hypercapnia, isocapnic-hypoxia, and on forearm blood flow during handgrip exercise, in COPD patients and healthy controls. This thesis demonstrates that the cerebrovascular and ventilatory responses to hypercapnia, but not hypoxia, are impaired in COPD. Vitamin C was found to augment the ventilatory response to hyperoxic-hypercapnia suggesting oxidative stress contributes to the overall ventilatory limitations in COPD. Dynamic cycling exercise (at a matched relative intensity), evoked a similar cerebrovascular response between COPD and controls, however, a modest increase in workload increased cerebral blood flow in COPD to levels greater than controls, reducing the cerebrovascular reserve capacity. Lastly, forearm blood flow in COPD patients during exercise was similar to controls, and was not affected by vitamin C. Overall, this series of experiments provides a better understanding of the complex systemic consequences of COPD in an integrated nature, thereby advancing knowledge in this important area of study.
- ItemOpen AccessDifferential Effects of High-Altitude Exposure on Markers of Oxidative Stress, Antioxidant Capacity and Iron Profiles, Supplementary Figures S1-S3, Rytz et al(2022-07-07) Rytz, Chantal; Pun, Matiram; Mawhinney, Jamie; Mounsey, Craig; Mura, Mathilde; Martin, Agnes; Pialoux, Vincent; Hartmann, Sara; Furian, Michael; Lopez, Ivan; Rawling, Jean; Soza, Daniel; Moraga, Fernando; Lichtblau, Mona; Bader, Patrick; Ulrich, Silvia; Bloch, Konrad; Frise, Matthew; Poulin, MarcSupplementary tables S1-S3 for manuscript entitled "Differential Effects of High-Altitude Exposure on Markers of Oxidative Stress, Antioxidant Capacity and Iron Profiles"
- ItemOpen AccessImpact of Intermittent Nocturnal Hypoxia on Human Cerebral Autoregulation(2021-11-23) Prsa, Andrew James; Poulin, Marc; Hanly, Patrick; Wilson, Richard; Raj, SatishObstructive sleep apnea (OSA) is a common sleep disorder that has been identified as an independent risk factor for the development of cardiovascular and cerebrovascular disease. OSA-induced intermittent hypoxia (IH) has been shown to be the principal mediator of vascular disease, however the specific pathophysiological mechanisms through which IH impacts human physiology is not fully understood. Individuals with OSA have been shown to have impaired cerebral autoregulation (CA), which may be a possible mechanism leading to OSA being an independent risk factor for stroke, however no studies have directly investigated how IH impacts dynamic CA. In addition, the impact of IH on human physiology has been predominately investigated during wakefulness, while individuals with OSA are exposed to IH during sleep. Therefore, the focus of the thesis was to investigate the impact of nocturnal IH on CA in healthy humans, in an effort to further understand the mechanisms by which IH disrupts physiology. The pilot study conducted in this thesis was performed as a secondary data analysis to investigate the effectiveness of the dynamic CA in healthy humans, during the transition from wakefulness to sleep, during one night of nocturnal IH exposure and during acute IH vs prolonged IH exposure, using data previously published (1). The novel findings from this study demonstrated that the dynamic CA effectiveness was similar during non-rapid eye movement (NREM) stage 2/3 sleep as compared to wakefulness; however, the reported decrease in the variability of VP and MAP oscillations during NREM stage 2/3 may help explain why the prevalence of stroke is lower during the first half of sleep. In addition, one night of nocturnal IH exposure does not impair dynamic CA and prolonged nocturnal IH exposure may not impact dynamic CA differently than acute nocturnal IH exposure.
- ItemOpen AccessModifiable and Non-modifiable Risk Factors in Cognitive and Cerebrovascular Aging(2017) Tyndall, Amanda; Poulin, Marc; Gordon, Grant; Hogan, David; Longman, R. StewartFor the first time in Canadian history, the number of Canadians over the age of 65 has surpassed those 14 years and younger making Canada an aging society. This trend is the same in all countries in the Developed World. With this increase of older adults in the world population, the study of modifiable and non-modifiable risk factors for healthy brain aging has become increasingly important. Normal brain aging is associated with a loss of some cognitive functions such as executive control, processing speed, learning, and memory functions. The trajectories of cognitive decline in older adults are influenced by modifiable risk factors such as hypertension and obesity, as well as non-modifiable risk genes (i.e., Apolipoprotein E) that potentially increase the risk of Alzheimer disease or related dementia. Physical activity has repeatedly been demonstrated to be effective in lowing cardiovascular risk factors while also protecting cerebrovascular reserve and cognitive functions. However, the potential relationship between multiple factors such as modifiable and non-modifiable risk factors, biomarkers, and physiological and psychological health in cognitive and cerebrovascular aging remains poorly understood. The Brain in Motion study was a quasi-experimental prospective cohort designed study which examined the effects of a six-month aerobic exercise intervention on cerebrovascular and cognitive function in healthy older adults. The study aimed to recruit 250 healthy, inactive, adults over the age of 55 years, and without mild cognitive impairment or dementia. Using pre-intervention data, Study I examined the effects of modifiable risk factors associated with Metabolic Syndrome and apolipoprotein E genotype on cerebrovascular function. Study II examined the contribution of genetic risk, subjective cognitive complaints, and vascular function during submaximal exercise on pre-intervention objective cognitive performance. Study III examined the influence of a six-month aerobic exercise intervention and exercise dose on cardiorespiratory fitness, cerebrovascular, and cognitive function. These results add to the growing literature suggesting that engagement of regular aerobic exercise improves cerebrovascular and cognitive functioning. In addition, these results provide insights on the influence of cerebrovascular mechanisms that are involved in promoting healthy brain aging.
- ItemOpen AccessRole of the Alzheimer's predisposition factor CD2AP in brain endothelial cells(2017) Gunn, Colin; Nguyen, Minh Dang; Gordon, Grant; Sanati Nezhad, Amir; Poulin, MarcAlzheimer disease (AD) is the most prevalent form of dementia in the elderly. Vascular degeneration plays a critical role in AD pathogenesis. For instance, APOE4 allele, the main genetic risk factor for AD, is linked to reduced cerebral blood flow and increased blood brain barrier (BBB) leakiness. CD2-associated protein (CD2AP) is an adaptor protein that regulates receptor endocytosis and recycling. Two single nucleotide polymorphisms in CD2AP are associated with higher risk for AD and levels of CD2AP are decreased in lymphocytes of sporadic AD patients. Recent human studies also show that CD2AP is linked to the burden of Aβ plaques, memory deficits and modulates AD symptoms in APOE4 patients. Interestingly, CD2AP is enriched in the brain microvascular endothelial cells (BMECs), a key component of the brain microvasculature. However, the basic functions of CD2AP in BMECs and its contribution to brain vasculature dysfunction in AD remain totally unknown. Here we show that siRNA-mediated depletion of CD2AP in both human brain endothelial cell line and mouse primary BMECs leads to the deregulation of proteins involved in AD pathogenesis. Of particular interest, we found that CD2AP interacts with one of these proteins, ApoER2, the receptor for ApoE that is targeted to degradation upon ligation by AD allele ApoE4. Similar to ApoE4, CD2AP loss reduced the levels of ApoER2. Finally, we discovered that downregulation of ApoER2 in CD2AP-depleted cells is modulated by Rab5 GTPase activity.
- ItemOpen AccessStudying cerebral hemodynamics and metabolism using simultaneous near-infrared spectroscopy and transcranial Doppler ultrasound: a hyperventilation and caffeine study(Wiley-Blackwell on behalf of The Physiological Society and the American Physiological Society, 2015-03-25) Yang, Runze; Brugniaux, Julien; Dhaliwal, Harinder; Beaudin, Andrew; Eliasziw, Misha; Poulin, Marc; Dunn, Jeff F.Caffeine is one of the most widely consumed psycho-stimulants in the world, yet little is known about its effects on brain oxygenation and metabolism. Using a double-blind, placebo-controlled, randomized cross-over study design, we combined transcranial Doppler ultrasound (TCD) and near-infrared spectroscopy (NIRS) to study caffeine's effect on middle cerebral artery peak blood flow velocity (Vp), brain tissue oxygenation (StO2), total hemoglobin (tHb), and cerebral oxygen metabolism (CMRO2) in five subjects. Hyperventilation-induced hypocapnia served as a control to verify the sensitivity of our measurements. During hypocapnia (~16 mmHg below resting values), Vp decreased by 40.0 ± 2.4% (95% CI, P < 0.001), while StO2 and tHb decreased by 2.9 ± 0.3% and 2.6 ± 0.4%, respectively (P = 0.003 and P = 0.002, respectively). CMRO2, calculated using the Fick equation, was reduced by 29.3 ± 9% compared to the isocapnic-euoxia baseline (P < 0.001). In the pharmacological experiments, there was a significant decrease in Vp, StO2, and tHb after ingestion of 200 mg of caffeine compared with placebo. There was no significant difference in CMRO2 between caffeine and placebo. Both showed a CMRO2 decline compared to baseline showing the importance of a placebo control. In conclusion, this study showed that profound hypocapnia impairs cerebral oxidative metabolism. We provide new insight into the effects of caffeine on cerebral hemodynamics. Moreover, this study showed that multimodal NIRS/TCD is an excellent tool for studying brain hemodynamic responses to pharmacological interventions and physiological challenges.
- ItemOpen AccessSustained Hypoxia and the Renin Angiotensin System(2014) Zalucky, Ann; Ahmed, Sofia; Hanly, Patrick; Poulin, MarcRationale: Chronic tissue hypoxia is considered to be the unifying pathway in chronic kidney disease (CKD) progression, yet the effect of systemic hypoxia as manifested in obstructive sleep apnea (OSA) is not well understood. Limited studies suggest OSA is associated with upregulation of the renin angiotensins system (RAS) a well described pathogenic factor renal dysfuction. We sought to determine the effect of nocturnal hypoxia on the hemodynamic and circulating response to angiotensin II (AngII) infusion. Methods: Thirty-one OSA patients (14 newly diagnosed; 17 from a historic cohort) and twelve obese controls were studied. Effective renal plasma flow (ERPF), determined by para-aminohippurate clearance technique, blood pressure (BP) and circulating components of the RAS (plasma renin activity (PRA) and aldosterone) were measured at baseline and in response to angiotensin-II (AngII) infusion. Patients were stratified according to hypoxia severity, into those with IH (mean nocturnal SaO2≥90%) and sustained hypoxia (SH, mean nocturnal SaO2<90%). Results: Patients with SH (P=0.015) and IH (P=0.01) had higher baseline filtration fractions (FF) than obese controls but circulating RAS components and BP were similar. The fall in ERPF in response to AngII, was less in patients with SH than IH and obese controls after both 3ng/kg/min (P=0.004) and 6ng/kg/min (P=0.001) reflecting greater renal RAS activity. There were no differences in the BP or PRA responses, but SH patients had a more robust aldosterone response to 6ng/kg/min AngII (p=0.023) than patients with IH. Conclusion: In patients with OSA, SH is associated with greater renal RAS activity than IH. OSA patients with this hypoxia profile may be more likely to experience the vascular consequences of elevated RAS activity such as hypertension and CKD.