Explore the vast range of titles available.

It is well established that sex differences exist in the manifestation of vascular diseases. Arterial stiffness (AS) has been associated with changes in cerebrovascular reactivity (CVR) and cognitive decline in aging. Specifically, older adults with increased AS show a decline on executive function (EF) tasks. Interestingly, the relationship between AS and CVR is more complex, where some studies show decreased CVR with increased AS, and others demonstrate preserved CVR despite higher AS. Here, we investigated the possible role of sex on these hemodynamic relationships. Acquisitions were completed in 48 older adults. Pseudo-continuous arterial spin labeling (pCASL) data were collected during a hypercapnia challenge. Aortic pulse wave velocity (PWV) data was acquired using cine phase contrast velocity series. Cognitive function was assessed with a comprehensive neuropsychological battery, and a composite score for EF was calculated using four cognitive tests from the neuropsychological battery. A moderation model test revealed that sex moderated the relationship between PWV and CVR and PWV and EF, but not between CVR and EF. Together, our results indicate that the relationships between central stiffness, cerebral hemodynamics and cognition are in part mediated by sex.

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, R_2^* and R_1 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 R_1, 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 R_1 related 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.Competing Interest StatementThe authors have declared no competing interest.Funder Information DeclaredNatural Sciences and Engineering Research Council of CanadaHeart and Stroke Foundation, https://ror.org/00qbpyp73Heart and Stroke Foundation New Investigator AwardHenry J.M. Barnett ScholarshipMichal and Renata Hornstein Chair in Cardiovascular Imaging and the Mirella and Lino Saputo research chair in cardiovascular health and the prevention of cognitive declineVascular Training PlatformCanadian Institutes of Health Research, https://ror.org/01gavpb45Brain Canada Foundation, https://ror.org/01bcmwk98

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.

Coronary 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. Thirty-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). Across all participants, VO₂peak was positively associated with CBF (β=0.32, p=0.02), and CVR (β=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 (β = 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 (β = −3.6, p = 0.02), consistent with adaptations in healthy aging being primarily driven by improved CBF without changes in CMRO₂. This 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.

Background: Coronary 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. Methods: Quantitative 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. Results: A 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. Conclusion: This 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.

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.

It is well established that sex differences exist in the manifestation of cardiovascular diseases. Arterial stiffness (AS) has been associated with changes in cerebrovascular reactivity (CVR) and cognitive decline in aging. Specifically, older adults with increased AS show a decline on executive function (EF) tasks. Interestingly, the relationship between AS and CVR is more complex, where some studies show decreased CVR with increased AS, and others demonstrate preserved CVR despite higher AS. We investigated the possible role of sex and hematocrit (HCT) on these hemodynamic relationships. Acquisitions were completed in 48 older adults. Dual-echo pCASL data were collected during a hypercapnia challenge. Aortic PWV data was acquired using cine phase contrast velocity series. A moderation model test revealed that sex moderated the relationship between PWV and CVR and PWV and EF. In addition, there was a significant effect of HCT on the sex differences observed in the moderation effect on EF. Together, our results indicate that the relationships between PWV, CVR and EF are in part mediated by sex and HCT.

Aging is accompanied by decreased grey matter volume (GMV), cerebral blood flow (CBF), and cerebrovascular reactivity (CVR), where the latter tends to decline the earliest in aging. Enhanced fitness in aging has been related to preservation of GMV and CBF, and in some cases CVR, although there are contradictory relationships reported between CVR and fitness. Therefore, to gain a better understanding of the complex interplay with fitness and GMV, CBF and CVR, it is necessary to study them concurrently. Here, we aimed to disentangle the interactions between these outcomes in healthy older adults. MRI acquisitions collected anatomical, CBF and CVR information in all participants, as well as VO2max. Results revealed decreased CVR was associated with increased fitness throughout large areas of the cerebral cortex. Within these regions it was found that lower fitness was associated with higher CBF and a slower hemodynamic response to hypercapnia. Overall, results indicate that the relationship between age, cerebral health and cerebral hemodynamics are complex. Future studies should collect other physiological outcomes in parallel with quantitative imaging, such as measures of carbon dioxide sensitivity and autoregulation, to further understand the intricacy of the effects fitness has on the aging brain, and how this may bias quantitative measures of cerebral health.

Background Chronic renal failure (CRF) is a progressive loss of renal function that lead to reduced sodium filtration and inappropriate suppression of tubular reabsorption that ultimately leads to volume expansion. The aim of this study was to study the efficacy of furosemide and tadalafil nanoforms compared to conventional forms against adenine-induced CRF rat-model. Methods Addition of 0.75% adenine to the diet of rats for 4 weeks gained general acceptance as a model to study kidney damage as this intervention mimicked most of the structural and functional changes seen in human chronic kidney disease Urine analysis, histopathological changes and immunohistochemical expression of caspase-3 and interleukin-1 beta (IL-1β) in renal tissues were performed. Results Our results showed that the combination of tadalafil and furosemide using conventional and nanoparticle formulations had better renoprotective effect than individual drugs. This was demonstrated by improvement of urinary, serum and renal tissue markers as indicative of organ damage. This was also reflected on the reduction of tubular expression of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Immunohistochemical studies showed that the deteriorated renal cellular changes indicated by increased expression of caspase-3 and IL-1β were greatly improved by the combined treatment particularly with the nanoforms. Conclusions The nanoforms of both furosemide and tadalafil had greater renopreventive effects compared with conventional forms against adenine-induced CRF in rats.

Background Hepatocyte death and a systemic inflammatory response are the outcome of a complex chain of events mediated by numerous inflammatory cells and chemical mediators. The point of this study was to find out if tadalafil and/or Lepidium sativum ( L. sativum ) could help people who have been exposed to carbon tetrachloride (CCL 4 ) and are experiencing acute moderate liver failure. This was especially true when the two were used together. Method and materials To cause mild liver failure 24 h before sacrifice, a single oral dosage of CCL 4 (2.5 mL/kg b.w.) (50% in olive oil) was utilized. Furthermore, immunohistochemical expression of nuclear factor kappa B (NF-κB) as well as histological abnormalities were performed on liver tissue. Results The results showed that tadalafil and/or L. sativum , especially in combination, performed well to cure acute mild liver failure caused by CCL 4 . This was demonstrated by a decrease in NF-κB expression in the liver tissue and an improvement in organ damage markers observed in the blood and liver tissues. Furthermore, such therapy reduced interleukin1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels in the liver tissue. It’s worth noting that the tested combination resulted in greater liver improvement. Conclusions According to the findings, tadalafil and L. sativum , particularly in combination, have the ability to protect the liver from the negative effects of CCL 4 exposure. Because of its capacity to improve liver function, restore redox equilibrium, and decrease inflammatory mediators, it is a prospective option for mitigating the negative effects of common environmental pollutants such as CCL 4 .