Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Neuroscience

Supervisor

Nagamatsu, Lindsay S.

Abstract

Type 2 diabetes is associated with neurocognitive deficits and increased risk for dementia, with high prevalence of diabetes occurring in old age. There are many known risk factors for diabetes, including physical inactivity, obesity, and prediabetes. Studies show that individuals who are at risk for diabetes (i.e., have one or more risk factors) already experience some brain deficits seen in diabetes. One way to combat these deficits is aerobic exercise; however, the effects of resistance exercise in this population are relatively unknown. The objectives of this thesis were to report on the current evidence of brain deficits in prediabetes, and to assess the feasibility and preliminary efficacy of resistance training to improve cognition and brain health (structure and function) in older adults at risk for diabetes. A systematic review of cross-sectional and longitudinal studies assessing brain dysfunction in prediabetes was conducted, as well as a 26-week pilot feasibility randomized controlled trial of resistance exercise among older adults at risk for diabetes (i.e., those living with prediabetes and/or obesity). The systematic review found that adults with prediabetes may experience deficits in structural connectivity, but whether deficits in brain volume and cerebrovascular health are present is somewhat inconclusive and may be due to inconsistencies across study methodologies. Results from the pilot feasibility trial found that resistance exercise, compared to balance and stretching exercise, may improve selective cognitive functions, mainly task-switching, selective attention, and response inhibition. Resistance exercise also led to less age-related decline in total brain volume, less hippocampal atrophy, and increased functional activation patterns that mimic that of younger adults and healthy older adults. When assessing feasibility, study adherence, retention, and self-reported enjoyment were high, but recruitment was shown to be challenging. As such, important recruitment recommendations for improving future trials are included in this thesis. In conclusion, resistance exercise may lead to some improvements in cognition and brain health in older adults at risk for diabetes, however a full-scale, powered RCT is needed to further explore these possible effects.

Summary for Lay Audience

Type 2 diabetes is a leading cause of disability among older adults and is associated with brain and cognitive deficits. Individuals who have one or more risk factors for diabetes including physical inactivity, obesity, or prediabetes (the state of having elevated blood sugar levels that are below the diabetes threshold) already show signs of similar impairment. Aerobic exercise, which aims to enhance cardiovascular function, is known to improve cognition and brain health (structure and function) in this population; however, the effects of resistance exercise, which aims to build muscle mass, are relatively unknown. The objectives of this thesis were to summarize the results from studies published to date regarding the brain deficits associated with prediabetes, and to determine whether resistance training may benefit cognition and neuroimaging outcomes in older adults at risk for diabetes (i.e., those with prediabetes and/or obesity) compared to balance and stretching exercises. The literature review found that studies assessing brain dysfunction in prediabetes have yielded largely mixed results, however deficits in structural connectivity may exist in prediabetes. The resistance exercise study found that this type of exercise may improve certain areas of cognition, such as the ability to switch focus between tasks. Additionally, neuroimaging findings from this study showed that resistance exercise may slow age- and disease-related brain shrinkage and lead to functional activation patterns that are seen in healthy adults. In summary, resistance exercise may improve cognition and brain health in older adults at risk for diabetes, however large-scale studies are needed to confirm these preliminary findings. Important recommendations for future trials are also included in this thesis.

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