Mobility in aging : clinical and neuroimaging studies

Introduction: The world’s population is aging at an unprecedented rate. By 2050, the number of adults older than 60 years will double from 10% to 20%. This trend has immense implications, due to the prevalence of impaired physical and cognitive functions among older adults. Therefore, it is important to understand the underlying mechanisms for these impairments and identify effective prevention strategies. White matter hyperintensities (WMHs) are common findings on MRI scans of older adults, and are associated with both physical and cognitive decline. Key risk factors for WMHs are related to metabolic and cardiovascular health. Thus, due to the established and significant benefit of targeted exercise training on metabolic and cardiovascular health in older adults, we hypothesized that one mechanism by which exercise, and specifically resistance training (RT), promotes physical and cognitive functions is by reducing WMH progression among older adults. Methods: We explored the associations between WMHs and physical and cognitive functions in Chapters 2 to 4. In Chapter 5, we presented a randomized controlled trial of 52-week RT. Participants were randomized to either once-weekly RT, twice-weekly RT, or twice-weekly balance and tone. We investigated the effect of RT on WMH progression. Results: Results from Chapters 2 and 3 suggest that reduced WMH progression may translate to maintained, or improved, physical and cognitive functions. Chapter 4 demonstrated that physical function is important for cognitive health. Chapter 5 provided proof-of-concept evidence that RT has beneficial effects on WMH progression, which may translate to improved physical and cognitive function. Specifically, we found that reduced WMH progression was significantly iii associated with improved gait speed. Moreover, our results suggest this effect may be dose-dependent, as the significant reduction in WMH progression was only observed among those in the twice-weekly RT group, and not in the once-weekly RT group. Conclusion: We provided converging evidence from four separate studies leading to the conclusion that RT has beneficial effects on WMH progression. Since WMHs are demonstrated to have significant associations with physical and cognitive dysfunctions, we believe that exercise-induced reductions of WMHs progression might translate to improvements in physical and cognitive functions in older adults.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat