Exercise for the aging brain : or are we just out biking?

Background: Age-related cognitive and physiological decline can in part be mitigated by increasing older adults’ physical exercise, but individuals respond differently, for example in cognitive domains such as working memory (WM). This thesis examines how high intensity exercise affects cognitive, neural, and physiological measures in older adults and explores how clinical findings can be translated into real world settings. Methods: This thesis includes four papers, and is based on the Umeå HIT study, which compared supramaximal high intensity interval training (HIT) to moderate intensity training (MIT) for older adults. Papers I-III used data from the Umeå HIT randomized controlled trial (RCT), while Paper IV used data from the Umeå HIT Home Study. The Umeå HIT RCT assessed the effects of 12 weeks of twice-weekly supramaximal HIT (20 minutes total, including 10 x 6 second intervals) compared to MIT (40 minutes total, including 3 x 8-minute bouts) among non-exercising older adults (n = 68, 66-79 years old, 56% women). Exercise intensity was individualized and controlled. Specifically, Paper I assessed cognitive, physiological, well-being and adverse event outcomes, of supramaximal HIT vs MIT. Paper II assessed effects of supramaximal HIT vs MIT on a functional magnetic resonance imaging WM task and examined the relationship between improved leg strength and WM manipulation task-related blood oxygen level dependent (BOLD) response and performance in an MRI subsample. Paper III tested baseline- and change-factors related to WM improvement. Paper IV, based on the Umeå HIT Home study (n = 11, 69-74 years old, 55% women) explored how the original supramaximal HIT protocol could be adapted to home use through a co-creation study involving participants who had exercised in the supramaximal HIT-group of the RCT. Results: Paper I found that irrespective of group, cardiorespiratory fitness and systolic and diastolic blood pressure were significantly improved, while global cognitive function was not affected. A significant group x time interaction was found in WM performance and isometric leg extensor strength in favor of supramaximal HIT. Paper II found that increased isometric leg extensor strength in the supramaximal HIT group was positively related to dorsolateral prefrontal cortex BOLD response, which in turn was related to increased WM performance. Paper III showed that the link between increased isometric leg extensor strength and improved WM also applied to a broader WM composite and the relationship was found in both exercise groups. It further showed that baseline white matter lesion load did not limit WM improvements following supramaximal HIT, unlike MIT. Upregulated brain derived neurotrophic factor was related to WM improvements, but differed by group, suggesting a stronger relationship in MIT. Paper IV identified alternative modalities to stationary bicycling and several adaptations to the supramaximal HIT protocol, including extending intervals to ten seconds, using an audio metronome to control intensity, and a mobile application for exercise delivery. Of the suggested modalities, chair stand intervals elicited similar acute physiological responses to supramaximal HIT on a stationary bicycle, intensity could be systematically modulated using a metronome, and the modality was considered safe. Conclusion: This thesis found that supramaximal HIT elicits similar- to superior effects on physiological and cognitive outcomes compared to MIT, despite half the exercise time. Furthermore, leg strength improvements were related to increased BOLD response in a key WM area, which in turn was related to improved WM performance in supramaximal HIT. Leg strength gains were further related to broader WM improvements irrespective of exercise group, indicating that muscular adaptations may be an important target for future exercise-cognition studies. Unlike MIT, supramaximal HIT-related WM gains were not limited by baseline white matter lesion load, and future studies should test this hypothesis directly. Adapting HIT for home use, especially with chair stand intervals, appears promising for future implementation, potentially enabling both cardiorespiratory and muscular gains. Future research should test the feasibility and effects of home-based supramaximal chair stand, as a step toward future implementation to real-world settings for older adults.