Biology subjects

Tremblay, S. A.

Publications and source records attributed to Tremblay, S. A..

10 recordsLinked to original sources

bioRxiv2026

Regional distribution of white matter hyperintensity burden in coronary artery disease and links with coronary revascularization procedure

IntroductionCoronary artery disease (CAD) increases the risk of cerebrovascular events, yet early brain injury in this population remains poorly characterized. White matter hyperintensities (WMHs), a biomarker of cerebrovascular lesions, are prevalent in CAD and are linked to risk of stroke. Beyond total burden, spatial distribution of WMHs carries pathological significance and is critical for understanding CAD-related injury. While clinical outcomes including coronary revascularization procedure and myocardial infarction influence CAD prognosis, their impact on WMH burden remains unclear. MethodsThis study investigated regional WMH burden in CAD and its relationship with clinical characteristics. 82 adults over 50 years participated, including 44 individuals with CAD and 38 controls. WMHs were segmented from fluid attenuated inversion recovery and T1-weighted MRI and categorized as total, periventricular, deep, and superficial regions. History of myocardial infarction and coronary revascularization (coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI)), was obtained from medical files. ResultsIndividuals with CAD exhibited higher total, periventricular, and deep WMH volumes than controls. Participants who underwent CABG had higher superficial WMH volumes than those with PCI, suggesting greater disease severity influences WMH burden. ConclusionCAD is characterized by a distinct pattern of cerebrovascular vulnerability, with revascularization procedures influencing WMH burden

neuroscience↗

bioRxiv2026

Coronary artery disease is linked with demyelination and iron deposition in white matter watershed areas

Coronary artery disease increases risk of cognitive decline and stroke and is associated with white matter alterations. However, the biological basis of these changes remains unclear. Myelin content and iron deposition are crucial measures of white matter health and can be measured with quantitative MRI. This study investigated whether myelin and iron alterations occur in coronary artery disease, and their relationship with cognition. In this cross-sectional study, 46 individuals with coronary artery disease and 40 healthy controls aged > 50 years, with normal cognition underwent 3T MRI and cognitive assessments. Quantitative MRI metrics (susceptibility, magnetization transfer saturation, R2* and R1 relaxation rates) were calculated in the border zones between adjacent arterial territories (watershed regions) and in the areas outside these borders (non-watershed regions). Relative to controls, the coronary artery disease group showed lower myelin and higher iron content, as measured by lower magnetization transfer saturation and R1, and higher susceptibility specifically in watershed regions. Importantly, these microstructural alterations were associated with poorer cognitive performance in the coronary artery disease group with lower magnetization transfer and R1related to poorer global cognition and with higher magnetic susceptibility with poorer verbal memory. These findings suggest that coronary artery disease is associated with demyelination and iron deposition in white matter, most prominently in watershed regions, which are known for their susceptibility to stroke. The association of these microstructural alterations with cognition highlights the role of white matter as a key vulnerable region and a promising focus for future mechanistic and therapeutic studies.

neuroscience↗

bioRxiv2025

Greater cardiorespiratory fitness is associated with higher cerebral blood flow and lower oxygen extraction fraction in healthy older adults

Aerobic exercise training promotes cardiovascular, brain and cognitive health. Regular exercise is associated with higher cardiorespiratory fitness, commonly assessed by peak oxygen uptake (VO2peak) during maximal effort testing. Higher cardiorespiratory fitness has been linked to preserved brain health, particularly higher grey matter volume and perfusion. The brain relies heavily on oxidative metabolism, yet the relationship between cardiorespiratory fitness and brain oxidative metabolism remains underexplored. This study investigated the association between VO2peak and two key cerebral metabolic parameters: the cerebral metabolic rate of oxygen consumption (CMRO2) and oxygen extraction fraction (OEF), which represents the balance between cerebral blood flow (CBF) and CMRO2. Thirty-seven healthy adults aged [≥]50 underwent maximal cardiopulmonary exercise testing for VO2peak assessment. Neuroimaging included dual calibrated functional MRI (dc-fMRI) and quantitative susceptibility mapping (QSM). Higher VO2peak correlated positively with higher CBF across whole-brain grey matter but showed no relationship with CMRO2. Conversely, higher VO2peak negatively correlated with lower OEF from both dc-fMRI and QSM. These findings suggest that greater cardiorespiratory fitness enhances cerebral perfusion without changing resting metabolic rate in healthy older adults, resulting in a reduced oxygen extraction. These results are consistent with exercise yielding improved vascular- metabolic coupling, which would reduce the likelihood of transient hypoxic episodes.

biophysics↗

bioRxiv2025

Preservation of cerebral vascular and metabolic health with greater cardiorespiratory fitness in coronary artery disease

BackgroundCoronary artery disease (CAD) is the leading cause of cardiovascular-related death globally. Beyond its cardiac consequences, CAD significantly impacts brain health, causing grey matter atrophy, reduced cerebral blood flow (CBF), impaired cerebrovascular reactivity (CVR), and cognitive decline. Recent evidence also highlights altered cerebral metabolism in CAD, characterized by reduced cerebral metabolic rate of oxygen consumption (CMRO2) and increased oxygen extraction fraction (OEF). Notably, impaired cardiorespiratory fitness, as measured by reduced peak oxygen uptake (VO2peak), is a hallmark of CAD progression and a strong prognostic marker of cardiovascular and neurological outcomes. Although VO2peak is associated with brain structural integrity and cognitive function, its relationship to cerebral vascular and metabolic function in CAD patients remains poorly understood. MethodsThirty-seven healthy individuals (age=65.35 {+/-} 8.31) and thirty-five patients with CAD (age=66.42 {+/-} 9.29) participated in this study. The objective was to determine whether higher cardiorespiratory fitness is associated with markers of cerebral health known to be impaired in CAD, in order to assess the potential of exercise as a strategy to mitigate CAD-related brain alterations. Cerebral vascular and metabolic biomarkers, including CBF, CVR, CMRO2, and OEF, were quantified using calibrated functional magnetic resonance imaging (MRI). Participants also completed a maximal cardiopulmonary exercise test on a bicycle ergometer to determine peak oxygen uptake (VO2peak). ResultsAcross all participants, VO2peak was positively associated with CBF ({beta}=0.32, p=0.02), and CVR ({beta}=0.002, p=0.04), in grey matter, confirming a link between aerobic fitness and vascular health across the cardiovascular health spectrum. However, metabolic markers exhibited group-specific patterns. Specifically, in CAD patients, VO2peak was positively associated with CMRO2 ({beta} = 0.08, p = 0.02), suggesting that reduced CMRO2 in CAD may be partially preserved by greater cardiorespiratory fitness. In contrast, a negative association between VO2peak and OEF was observed exclusively in healthy controls ({beta} = -3.6, p = 0.02), consistent with adaptations in healthy aging being primarily driven by improved CBF without changes in CMRO2. ConclusionThis study shows that higher cardiorespiratory fitness is associated with improved cerebral vascular and metabolic function, with distinct patterns observed between healthy individuals and those with CAD. In patients with CAD, greater fitness appears to preserve cerebral oxygen metabolism, while in healthy individuals, fitness is primarily linked to enhanced perfusion. These findings support the role of aerobic exercise as a promising strategy to counteract CAD-related brain alterations, emphasizing the importance of targeting cardiorespiratory fitness in both prevention and rehabilitation settings.

biophysics↗

bioRxiv2025

The Impact of Coronary Artery Disease on Brain Vascular and Metabolic Health: Links to Cognitive Function

BackgroundCoronary artery disease (CAD) is the leading cause of mortality worldwide and is associated with an increased incidence of cognitive decline, however the pathological mechanisms linking CAD to brain and cognitive health remain unclear. Prior research has identified regional deficits in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), a measure of vascular reserve, in patients with CAD. However, the impact of these cerebrovascular deficits on cognition has not been explored, nor has the effect of CAD on cerebral metabolic health. This study aims to fill these gaps by investigating how CAD influences cerebral vascular and metabolic health, and how these alterations relate to cognitive function across multiple domains. MethodsQuantitative magnetic resonance imaging (MRI) was employed to measure a comprehensive profile of cerebral vascular and metabolic health, including CBF, CVR, cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF). Cognition was assessed using a validated neuropsychological battery from which composite scores were extracted, reflecting executive functions, working memory, processing speed, and verbal episodic memory. ResultsA total of 35 patients with CAD and 37 healthy controls were included in the final analysis. Patients with CAD demonstrated widespread impairments in both cerebral vascular and metabolic health, characterized by lower CBF, CVR, and CMRO2, and increased OEF, indicative of insufficient oxygen delivery. Notably, lower CVR was associated with poorer executive function, suggesting a specific role of vascular reserve for preserving executive functions. Furthermore, higher OEF was associated with poorer working memory, showing the importance of preserved oxygen consumption for maintaining cognitive function. ConclusionThis study reveals that CAD is associated with impaired cerebral vascular and metabolic health, providing a pathological basis for cognitive decline. Specifically, reduced CVR and elevated OEF emerged as sensitive biomarkers linking impaired brain health and cognition. These markers hold promise for guiding future interventions aimed at preserving cognitive health in patients with CAD. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LICoronary artery disease is associated with an increased incidence of cognitive decline but the biological mechanisms underlying these changes in cognition are unclear. C_LIO_LIThis is the first study to comprehensively demonstrate profound and widespread deficits in both cerebral vascular and oxidative metabolic health in patients with coronary artery disease. C_LIO_LICerebrovascular reactivity and oxygen extraction fraction may be sensitive biomarkers of early cognitive decline in coronary artery disease. C_LI What Are the Clinical Implications?O_LIThe widespread impairments in cerebral vascular and metabolic health suggest that coronary artery disease has profound consequences on the brain. C_LIO_LIPoor vascular reserve and an imbalance between oxygen delivery and usage may be crucial determinants of cognitive health. These results highlight the limitations of traditional biomarkers in understanding the brains vulnerability and the need for these novel and quantitative biomarkers of cerebral physiological health. C_LIO_LIThese findings suggest that cerebral vascular and metabolic deficits exist even in the absence of overt cognitive decline in coronary artery disease, emphasizing the need for early detection and preventative strategies. C_LI

biophysics↗

bioRxiv2025

Multivariate white matter microstructure alterations in older adults with coronary artery disease

Patients with coronary artery disease (CAD) face an increased risk of cognitive impairment, dementia, and stroke. While white matter (WM) lesions are frequently reported in patients with CAD, the effects on WM microstructure alterations remain largely unknown. We aimed to identify WM microstructural alterations in individuals with CAD compared to healthy controls (HC), and to examine their relationships with cognitive performance. Forty-three (43) patients with CAD and 36 HC aged 50 and older underwent comprehensive neuropsychological testing and multi-modal 3T MRI. A novel multivariate approach - the Mahalanobis distance (D2) - was used to quantify WM abnormalities as the amount of deviation from the HC reference group. D2 integrates multiple MRI-derived diffusion-weighted imaging, R1 relaxometry, and magnetization transfer imaging metrics, while accounting for covariance between metrics. Relationships between WM D2 and cognition (executive function and processing speed) were also assessed. Compared to HCs, patients with CAD had higher D2 values in the whole WM (p=0.009) and in the territories right anterior, bilateral middle, and right posterior cerebral artery territories (p<0.05). Myelin-sensitive metrics, particularly R1 relaxation rate and MT saturation (MTsat), were the most important contributors to D2. Processing speed was positively associated with greater R1 in both the whole WM and left middle cerebral artery territory. These findings suggest that greater WM microstructural alterations observed in patients with CAD were mainly driven by differences in myelin content, as R1 and MTsat were the most important contributors. These alterations may contribute to a heightened risk of cognitive impairment.

neuroscience↗

bioRxiv2024

Sex and APOE4-specific links between cardiometabolic risk factors and white matter alterations in individuals with a family history of Alzheimer's disease

INTRODUCTIONWhite matter (WM) alterations are among the earliest changes in Alzheimers disease (AD), yet limited work has comprehensively characterized the effects of AD risk factors on WM. METHODSIn older adults with a family history of AD, we investigated the sex-specific and APOE genotype-related relationships between WM microstructure and risk factors. Multiple MRI-derived metrics were integrated using a multivariate approach based on the Mahalanobis distance (D2). The links between WM D2 and cognition were also explored. RESULTSWM D2 in several regions was associated with high systolic blood pressure, BMI, and glycated hemoglobin, and low cholesterol, in both males and females. APOE4+ displayed a distinct risk pattern, with LDL-cholesterol having a detrimental effect only in carriers, and this pattern was linked to immediate memory performance. Myelination was the main mechanism underlying WM alterations. DISCUSSIONOur findings reveal that combined exposure to multiple cardiometabolic risk factors negatively impacts microstructural health, which may subsequently affect cognition. Notably, APOE4 carriers exhibited a different risk pattern, especially in the role of LDL, suggesting distinct underlying mechanisms in this group.

neuroscience↗

bioRxiv2024

MVComp toolbox: MultiVariate Comparisons of brain MRI features accounting for common information across metrics

Multivariate approaches have recently gained in popularity to address the physiological unspecificity of neuroimaging metrics and to better characterize the complexity of biological processes underlying behavior. However, commonly used approaches are biased by the intrinsic associations between variables, or they are computationally expensive and may be more complicated to implement than standard univariate approaches. Here, we propose using the Mahalanobis distance (D2), an individual-level measure of deviation relative to a reference distribution that accounts for covariance between metrics. To facilitate its use, we introduce an open-source python-based tool for computing D2 relative to a reference group or within a single individual: the MultiVariate Comparison (MVComp) toolbox. The toolbox allows different levels of analysis (i.e., group-or subject-level), resolutions (e.g., voxel-wise, ROI-wise) and dimensions considered (e.g., combining MRI metrics or WM tracts). Several example cases are presented to showcase the wide range of possible applications of MVComp and to demonstrate the functionality of the toolbox. The D2 framework was applied to the assessment of white matter (WM) microstructure at 1) the group-level, where D2 can be computed between a subject and a reference group to yield an individualized measure of deviation. We observed that clustering applied to D2 in the corpus callosum yields parcellations that highly resemble known topography based on neuroanatomy, suggesting that D2 provides an integrative index that meaningfully reflects the underlying microstructure. 2) At the subject level, D2 was computed between voxels to obtain a measure of (dis)similarity. The loadings of each MRI metric (i.e., its relative contribution to D2) were then extracted in voxels of interest to showcase a useful option of the MVComp toolbox. These relative contributions can provide important insights into the physiological underpinnings of differences observed. Integrative multivariate models are crucial to expand our understanding of the complex brain-behavior relationships and the multiple factors underlying disease development and progression. Our toolbox facilitates the implementation of a useful multivariate method, making it more widely accessible.

neuroscience↗

bioRxiv2021

Motor Sequences - Separating The Sequence From The Motor. A longitudinal rsfMRI Study

In motor learning, sequence-specificity, i.e. the learning of specific sequential associations, has predominantly been studied using task-based fMRI paradigms. However, offline changes in resting state functional connectivity after sequence-specific motor learning are less well understood. Previous research has established that plastic changes following motor learning can be divided into stages including fast learning, slow learning and retention. A description of how resting state functional connectivity after sequence-specific motor sequence learning (MSL) develops across these stages is missing. This study aimed to identify plastic alterations in whole-brain functional connectivity after learning a complex motor sequence by contrasting an active group who learned a complex sequence with a control group who performed a control task matched for motor execution. Resting state fMRI and behavioural performance were collected in both groups over the course of 5 consecutive training days and at follow-up after 12 days to encompass fast learning, slow learning, overall learning and retention. Between-group interaction analyses showed sequence-specific decreases in functional connectivity during overall learning in the right supplementary motor area (SMA). We found that connectivity changes in key regions of the motor network including the superior parietal cortex (SPC) and primary motor cortex (M1) were not a result of sequence-specific learning but were instead linked to motor execution. Our study confirms the sequence-specific role of SMAthat has previously been identified in online task-based learning studies, and extends it to resting state network changes after sequence-specific MSL.

neuroscience↗

bioRxiv2020

White matter microstructural changes in short-term learning of a continuous visuomotor sequence

Efficient neural transmission is crucial for optimal brain function, yet the plastic potential of white matter (WM) has long been overlooked. Growing evidence now shows that modifications to axons and myelin occur not only as a result of long-term learning, but also after short training periods. Motor sequence learning (MSL), a common paradigm used to study neuroplasticity, occurs in overlapping learning stages and different neural circuits are involved in each stage. However, most studies investigating short-term WM plasticity have used a pre-post design, in which the temporal dynamics of changes across learning stages cannot be assessed. In this study, we used multiple magnetic resonance imaging (MRI) scans at 7 Tesla to investigate changes in WM in a group learning a complex visuomotor sequence (LRN) and in a control group (SMP) performing a simple sequence, for 5 consecutive days. Consistent with behavioral results, where most improvements occurred between the two first days, structural changes in WM were observed only in the early phase of learning (d1-d2), and in overall learning (d1-d5). In LRNs, WM microstructure was altered in the tracts underlying the primary motor and sensorimotor cortices. Moreover, our structural findings in WM were related to changes in functional connectivity, assessed with resting-state functional MRI data in the same cohort, through analyses in regions of interest (ROIs). Significant changes in WM microstructure were found in a ROI underlying the right supplementary motor area. Together, our findings provide evidence for highly dynamic WM plasticity in the sensorimotor network during short-term MSL.

neuroscience↗