Investigating the mediating impact of insulin resistance on the physical activity and brain beta-amyloid relationship in cognitively unimpaired older adults. — The Association Specialists
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  3. Investigating the mediating impact of insulin resistance on the physical activity and brain beta-amyloid relationship in cognitively unimpaired older adults.

Investigating the mediating impact of insulin resistance on the physical activity and brain beta-amyloid relationship in cognitively unimpaired older adults. (#5)

Michael Slee 1 , Stephanie R Rainey-Smith 1 2 3 4 , Victor L Villemagne 5 6 7 , Hamid R Sohrabi 1 2 3 8 , Kevin Taddei 2 3 , David Ames 9 10 11 , Vincent Doré 5 , Paul Maruff 12 13 , Simon M Laws 7 14 , Colin L Matsers 10 , Christopher C Rowe 5 10 , Ralph N Martins 2 3 8 , Kirk I Erickson 15 16 , Timothy J Fairchild 1 , Belinda M Brown 1 2 3
  1. Centre for Healthy Aging, Healthy Futures Institute, Murdoch University, Murdoch, WA, Australia
  2. Australian Alzheimer's Research Foundation, Perth, WA, Australia
  3. School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
  4. School of Psychological Science, University of Western Australia, Nedlands, WA, Australia
  5. Department of Molecular Imaging & Therapy, Austin Health, Melbourne, VIC
  6. Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
  7. Centre for Precision Health, Edith Cowan University, Perth, WA, Australia
  8. Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia
  9. National Ageing Research Institute, Melbourne, VIC, Australia
  10. The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia
  11. Academic Unit for Psychiatry of Old Age, St George's Hospital, University of Melbourne, Melbourne, VIC, Australia
  12. Cogstate Ltd, Melbourne, VIC, Australia
  13. The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia
  14. Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
  15. Neuroscience Institute, AdventHealth, Orlando, FL, USA
  16. Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA

Objective: The association between Type 2 diabetes and Alzheimer’s disease (AD) suggest common pathological mechanisms in the brain; insulin resistance (IR) can impair insulin pathway signalling, that aids in reduced beta amyloid (Aβ) accumulation. Studies have shown that physical activity (PA) is associated with lower brain Aβ burden and can reduce IR. To date no study has assessed the mediating impact that IR has on the PA ~ brain Aβ relationship in humans. Observational data was used to examine any mediation impact of IR on the PA ~ brain Aβ load relationship through statistical mediation methods.

Methods: PA, Aβ imaging and metabolic measures, from 367 cognitively unimpaired older adults were used. IR was assessed using the Homeostatic Model Assessment for Insulin Resistance. Mediation analysis statistically examined the relationships between physical activity and Aβ directly and then indirectly via IR impact. Participants were also stratified into diabetic and non-diabetics groups.

Result: No mediation effect of IR on the PA and brain Aβ relationship was observed [95% CI -0.0001 to 0.0000]. No direct effect was observed between PA and brain Aβ (p = 0.0544) or PA and IR (p = 0.4905) or IR and brain Aβ (p = 0.4052). These results were also seen within the two diabetic stratified groups except for a direct effect observed between PA and brain Aβ (p = 0.0154) in the diabetic group only.

Conclusion: Our study did not show that IR mediated the relationship between PA levels and brain Aβ in cognitively unimpaired older adults.