Asymptomatic Carotid Stenosis and Mobility Function with Exercise Intervention (ACCOF-Ex)

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Asymptomatic carotid artery stenosis (ACAS) affects ~10% of older adults. The clinical outcome of stroke has been studied extensively. Recent literature, including our preliminary data, demonstrates that moderate (50- 69%) and severe (≥70%) ACAS are also associated with falls and balance and mobility dysfunction. The primary hypothesized factor underlying these deficits is cerebral hypoperfusion. In patients with severe ACAS, carotid revascularization has been shown to improve perfusion, as well as balance and mobility dysfunction. Patients with moderate stenosis, who form a much larger proportion of ACAS patients, do not qualify for surgery. With 830,000 Veterans estimated to have moderate ACAS, developing targeted treatment strategies to improve bal- ance and mobility function is critical to prevent disability and preserve functional independence. Targeted aerobic and balance exercises increase cerebral perfusion and improve balance and mobility func- tion in older adults without carotid stenosis. Based on these findings, we hypothesize that an aerobic and chal- lenging balance (AeroBal) exercise intervention will improve balance and mobility function in Veterans with mod- erate ACAS while enhancing cerebral perfusion. For this CDA-2, I propose a randomized study to evaluate the effects of a 12-week supervised AeroBal exercise program on balance and mobility function in patients with moderate ACAS versus standard-of-care controls. Towards this goal, I propose the following Aims: Aim 1. Determine the effect of a 12-week supervised AeroBal exercise program on balance and mobility function in Veterans with moderate ACAS. Hypothesis: Supervised AeroBal exercises plus standard-of-care will lead to greater improvement in balance and mobility (primary outcome: Mini Balance Evaluation Systems Test [Mini BESTest]) compared to standard-of-care vascular risk-factor reduction alone in patients with moderate ACAS. Secondary outcome measures will include rate of prospective falls and measures of physical function. Aim 2. Determine the effect of a 12-week supervised AeroBal exercise program on cerebral perfusion in the presence of moderate ACAS. Hypothesis: Supervised AeroBal exercises plus standard-of-care will lead to greater improvement in cerebral perfusion (primary measure: perfusion-weighted magnetic resonance imaging and secondary measure: transcranial Doppler) compared to standard-of-care vascular risk-factor reduction alone in patients with moderate carotid stenosis. We will also explore functional near-infrared spectroscopy as a novel measure of perfusion that is ideal for clinical translation as it assesses perfusion during mobility tasks. An exploratory analysis will examine the relationship between changes in balance and mobility function and changes in cerebral perfusion. Hypothesis: Exercise-induced changes in balance and mobility function will be related to changes in cerebral perfusion independent of changes in known vascular risk factors. The identification of exercise as an intervention to improve cerebral perfusion and balance and mobility func- tion in patients with moderate ACAS could lead to significant changes in the clinical management, functional independence, and quality of life of this patient population who are not candidates for surgery. My long-term goal is to become an independent VA investigator in targeted interventions to preserve and improve functional inde- pendence in ACAS patients. More specifically, I aim to elucidate the role that cerebral perfusion plays in the development of balance and mobility dysfunction in this VA patient subset. Thus, by being a VA surgeon-scien- tist, I aim to improve the clinical outcomes of not only my patients, but the broader vascular patient population via exercise interventions. With the proposed VA CDA-2 award, I will be able to acquire additional education and mentorship in balance and mobility function assessments, exercise intervention, clinical trial design and statistical analysis, advanced cerebrovascular imaging, and leadership and management of a study team. The skills and experience derived from this opportunity will prepare me for a career as an independent investigator within the VA RR&D.