Influence of exercise training and intensity on cerebral blood flow regulation and cognitive function in mid-life adults with cardiovascular disease.

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PROJECT SUMMARY Rates of cognitive impairment and dementia are on the rise with incidence set to triple by 2050. Mid-life is an important time for prevention strategies, as around 30% of cognitive impairment has been attributed to modifiable risk factors at this life stage. Furthermore, adults with cardiovascular disease (CVD) are at even higher risk of cognitive decline, which is further accelerated by a cardiac-related event. Cerebral hypoperfusion (reduced brain blood flow) appears to be a significant contributor to cognitive decline, which can occur as a result of vascular dysfunction and impairment of cerebral blood flow (CBF) regulation. In contrast, higher cardiorespiratory fitness shows protection against cognitive decline, brain atrophy, and reductions in CBF. Therefore, strategies that improve vascular function, cardiorespiratory fitness, and other modifiable CVD risk factors, such as exercise, should be further investigated as prevention strategies in mid-life adults at high risk of cognitive decline. Cardiac rehabilitation (exercise and risk factor modification program) may provide an ideal preventative strategy to attenuate the cognitive decline in mid-life adults who have had a cardiac-related event. Furthermore, in patients attending cardiac rehabilitation, high intensity interval training (HIIT) has been shown to double improvements in cardiorespiratory fitness and vascular function, compared with moderate intensity continuous training (MICT). Whether these greater improvements translate into greater improvements for cerebrovascular function, CBF regulation, and cognitive function is unknown. This randomized controlled trial involving mid-life adults with CVD, will investigate the effect of exercise intensity (HIIT compared with MICT) during a 12-week cardiac rehabilitation (3 sessions/week) on CBF regulation and cognitive function. We hypothesize that HIIT during cardiac rehabilitation will lead to greater improvements in CBF regulation (as cerebrovascular reactivity) than MICT, and as a result we hypothesize that HIIT will lead to greater improvements in cognitive function compared with MICT. Furthermore, this study will include an observational control group of patients who decline cardiac rehabilitation, to investigate the potential benefit for exercise-based cardiac rehabilitation compared with no cardiac rehabilitation. We hypothesize that patients attending exercise-based cardiac rehabilitation will have greater improvements in CBF regulation (as cerebrovascular reactivity) and cognitive function, compared with patients who do not attend cardiac rehabilitation. We will also explore changes in resting CBF, brain structure, neurotrophic biomarkers, and ambulatory blood pressure, as well as other indices of CBF regulation. This exploratory study will help to generate pilot data that will aid in the design of ongoing research and proposals for larger grants investigating 1) specific exercise prescription to enhance cognitive health in mid- life adults, and 2) potential benefits for cardiac rehabilitation participation in this population.