Exploring real-time alterations in cerebral perfusion, BOLD signal, and cognition during physical activity

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ABSTRACT Aging is associated with pervasive neural and cognitive decline, which is further accelerated by poor cardiorespiratory (CR) function. This intersection of cardiac and respiratory function with brain and cognitive aging is further highlighted by research demonstrating that vascular dysfunction is a major component of age- associated cognitive decline, likely underpinned by alterations in cerebrovascular reactivity. Importantly, cardiac, vascular, and respiratory functions change dynamically in response to physiological demands – changes that are not captured by the standard brain imaging approach, when subjects typically undergo Magnetic Resonance Imaging (MRI) while lying still. A more sensitive approach, therefore, is to use neuroimaging during physical activity, when cardiac, vascular, and respiratory functions are taxed. Extant studies using physical activity to elicit a CR challenge implement imaging methods that lack the spatial resolution to examine regional changes or acquire imaging data after the CR challenge, by which time heart rate and respiration have returned to baseline, thereby failing to probe a critical period that may be most sensitive to age-related changes in cerebral hemodynamics. Here we propose to elucidate neurovascular mechanisms of age-associated decline through the implementation of a novel, naturalistic, CR challenge during simultaneous functional MRI (fMRI). We do so using a unique “cardiostepper” device, a Stairmaster-like piece of equipment that attaches to the MRI table. By manipulating the intensity of physical activity during fMRI, we are able to observe real-time changes in neurophysiology as a function of CR workload. This innovation allows for the assessment of cerebral hemodynamics during physical activity in a similar way that a ‘cardiac stress test’ (asking patients to walk/run on a treadmill at increasing intensity) is used clinically to identify cardiac abnormalities that are not present at rest and only identifiable when the patient is under cardiopulmonary duress. In this proposal, 25 young and 25 older adults will undergo cognitive testing, maximal cardiopulmonary exercise testing (CPET), and MRI during exercise challenge. Specific Aim 1 is focused on the elucidation of age-related changes in (blood oxygenation level dependent) BOLD response during physical activity. During fMRI, a block-design CR challenge will be implemented. To explore downstream cerebral benefits of exercise, we will also acquire arterial spin labeling (ASL) MRI data pre- and post-CR challenge to examine whether cerebral blood flow is augmented subsequent to an exercise stimulus. Specific Aim 2 will examine whether the BOLD response during CR challenge is correlated with cognitive performance among young and older adults. The development of a paradigm to examine regionally-specific alterations in cerebral hemodynamics during physical activity, which places the CR system under duress, has the potential to serve as a biomarker for those at risk for neural and cognitive decline.