Doctoral Thesis
The association between physical activity and Alzheimer’s disease biomarkers in cognitively unimpaired older adults
Murdoch University
Doctor of Philosophy (PhD), Murdoch University
2025
DOI:
https://doi.org/10.60867/00000106
Abstract
Preventing dementia, particularly Alzheimer’s disease (AD), is a major global health priority. The exact cause of AD is unclear; however, AD biomarkers like beta amyloid (Aβ) and tau are linked with AD progression. Physical activity is associated with reduced AD risk in older adults; and animal studies show that exercise reduces brain Aβ and tau, yet human studies remain inconclusive.
Most human studies examining the relationship between physical activity and AD biomarkers are cross-sectional. Chapter 3 of my thesis addresses this methodological issue by using longitudinal data to track the relationship between physical activity and brain Aβ in cognitively unimpaired older adults over time. No associations between baseline physical activity and longitudinal measures of brain Aβ were observed. Additionally, physical activity trajectory for individuals with high and low Aβ levels were compared, showing no difference.
Given that type 2 diabetes (T2D) raises AD risk, insulin resistance, a T2D hallmark that can be reduced by physical activity, was evaluated as a possible mediator of the physical activity and Aβ relationship. We conducted a scoping review (Chapter 4) revealing no previous research that investigated insulin resistance as a mediator of the physical activity and brain Aβ relationship. Chapter 5 addressed this gap, assessing the mediation of self-reported physical activity and brain PET Aβ by insulin resistance using the Homeostatic Model Assessment for Insulin Resistance (HOMAIR) in cognitively unimpaired older adults, with no mediation by HOMA-IR found.
Chapter 6 examined another cohort of cognitively unimpaired older adults, this time examining physical activity measured via actigraphy and including blood-based measures of tau as well as PET Aβ. No mediation was found between physical activity and brain Aβ via insulin resistance. However, physical activity was indirectly associated with p-tau217 levels through its influence on insulin resistance.
In conclusion, this thesis did not show evidence of a relationship between physical activity and brain Aβ, either directly or via insulin resistance. It did, however, provide evidence that physical activity may be associated with p-tau levels, suggesting a possible pathway in which physical activity can moderate AD risk. This finding suggests that future research evaluating how physical activity can influence tau processes should be focused on to further understand the strength of physical activity as a modifiable risk factor for AD.
Details
- Title
- The association between physical activity and Alzheimer’s disease biomarkers in cognitively unimpaired older adults
- Authors/Creators
- Michael Slee
- Contributors
- Belinda Brown (Supervisor) - Murdoch University, Centre for Healthy Ageing
- Awarding Institution
- Murdoch University; Doctor of Philosophy (PhD)
- Publisher
- Murdoch University
- Identifiers
- 991005885953907891
- Murdoch Affiliation
- School of Allied Health
- Resource Type
- Doctoral Thesis
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