No abstract

Aging is accompanied by vascular and structural changes in the brain, which include decreased grey matter volume (GMV), cerebral blood flow (CBF), and cerebrovascular reactivity (CVR). 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. To gain a better understanding of the complex interplay between fitness and GMV, CBF and CVR, the present study assessed these factors concurrently. Data from 50 participants, aged 55 to 72, were used to derive GMV, CBF, CVR and VO2peak. Results revealed that lower CVR was associated with higher VO2peak throughout large areas of the cerebral cortex. Within these regions lower fitness was associated with higher CBF and a faster hemodynamic response to hypercapnia. Overall, our results indicate that the relationships between age, fitness, cerebral health and cerebral hemodynamics are complex, likely involving changes in chemosensitivity and autoregulation in addition to changes in arterial stiffness. Future studies should collect other physiological outcomes in parallel with quantitative imaging, such as measures of chemosensitivity and autoregulation, to further understand the intricate effects of fitness on the aging brain, and how this may bias quantitative measures of cerebral health.

Background: Vascular risk factors such as arterial stiffness play an important role in the etiology of Alzheimer’s disease (AD), presumably due to the emergence of white matter lesions. However, the impact of arterial stiffness to white matter structure involved in the etiology of AD, including the corpus callosum remains poorly understood. Objective: The aims of the study are to better understand the relationship between arterial stiffness, white matter microstructure, and perfusion of the corpus callosum in older adults. Methods: Arterial stiffness was estimated using the gold standard measure of carotid-femoral pulse wave velocity (cfPWV). Cognitive performance was evaluated with the Trail Making Test part B-A. Neurite orientation dispersion and density imaging was used to obtain microstructural information such as neurite density and extracellular water diffusion. The cerebral blood flow was estimated using arterial spin labelling. Results: cfPWV better predicts the microstructural integrity of the corpus callosum when compared with other index of vascular aging (the augmentation index, the systolic blood pressure, and the pulse pressure). In particular, significant associations were found between the cfPWV, an alteration of the extracellular water diffusion, and a neuronal density increase in the body of the corpus callosum which was also correlated with the performance in cognitive flexibility. Conclusion: Our results suggest that arterial stiffness is associated with an alteration of brain integrity which impacts cognitive function in older adults.

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.

Highlights• This study investigates the role of sex on cerebrovascular measures of brain health and congition• Sex moderates the relationship between PWV, cerebrovascular reactivity and cognition• Hematocrit influences the sex differences observed AbstractIt 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 VO 2 max. 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.