Associations between Physical Activity and Cognition across the Spectrum from Mild Cognitive Impairment to Lewy Body Dementia and Adaptations to Robust Anabolic Exercise Interventions

Abstract

Globally, it is estimated that 50 million people are currently living with dementia, which is expected to reach 75 million by the end of this decade. Recently, there has been increasing interest in the use of lifestyle interventions to delay both the onset and progression of dementia following a growing list of failed pharmaceutical trials. Habitual physical activity is one such target for lifestyle intervention due to promising longitudinal evidence linking higher levels of physical activity with greater cognition, slower cognitive decline and decreased risk of developing Alzheimer’s disease and all-cause dementia. Physical activity itself is associated with various clinical characteristics that are amenable to exercise intervention in older adults, including but not limited to, physical function, strength, muscle mass, cognition, psychological health, and functional independence. Robust anabolic exercise such as progressive resistance training (PRT) is a promising intervention which can augment cognition in healthy older as well many of the associated clinical characteristics that are significantly influenced by the catabolic processes observed within dementia, such as sarcopenia, frailty and malnutrition. However, the relationship between cognition and physical activity, and extent to which these clinical characteristics are modifiable following robust anabolic exercise, remain largely unanswered. Thus, the aims of this thesis are to (1) characterise levels of physical activity and sedentary time in populations with varying degrees of cognitive impairment, (2) evaluate the relationship between physical activity and sedentary behaviour with cognition across the cognitive spectrum, and subsequently (3) evaluate the effects of robust anabolic exercise on change in cognition and changes in physical activity and sedentary behaviour, and whether these changes are related to each other. To investigate these aims, we have evaluated two very different cohorts along the cognitive impairment spectrum: mild cognitive impairment (MCI) and Lewy body dementia (LBD). Specifically, MCI represents a stage of cognitive impairment where there is minimal functional impairment in daily activities, and where there is not necessarily an underlying pathological process causing impairment. Conversely, LBD represents a severe, rapidly progressing form of dementia with significant pathological underpinning that results in extensive cognitive, psychiatric, movement and autonomic symptoms. The relationship between physical activity and cognition, and subsequent response to intervention may differ with increasing disease severity, frailty, and functional limitations. Therefore, this thesis was able to rigorously evaluate these associations across the spectrum of cognitive impairment. There was a range of relevant of scientific methodologies and study designs included throughout this thesis in order to address these aims. The seven chapters of this thesis include a systematic review, cross-sectional observational studies, a randomised controlled trial, a protocol with rationale, a novel pilot study, and a thorough case report. Collectively, these chapters have provided a comprehensive picture of both the levels of physical activity and cognition in older adults with cognitive impairment, as well as their association with a diverse range of modifiable clinical characteristics. These findings provide robust rationale for the use of anabolic exercise in these cohorts to address modifiable aspects of their chronic diseases and geriatric syndromes, most notably frailty and disability. Lastly, the novelty of our findings provide a foundation for future investigations to further explore these associations within other types of cognitive impairment and refine effective interventions to attenuate cognitive decline and the risk of dementia.