Medium‐chain fatty acids in combination with a multidomain lifestyle intervention in Alzheimer's disease prevention: Protocol design to study implementation.

Background: Alzheimer's disease (AD) neuropathology begins 20 to 30 years before clinical diagnosis. Thus, there is an opportunity to implement strategies to prevent the progression of AD. Insulin resistance in the brain causes a disruption in glucose utilisation. Medium‐chain fatty acids (MCFA) are readily available substrates for the synthesis of ketone bodies (KB), which are an alternative brain fuel not controlled by insulin. A constant supply of KB may close the energy gap in the AD‐prone brain, and in doing so prevent or delay symptom onset, or protect the brain from further degeneration. There is increasing evidence that multidomain lifestyle interventions with dietary components significantly impact cognitive decline. Yet, these interventions have not considered the effects MCFA supplementation, to ensure sufficient energy for the brain. Method: This is a phase II placebo‐controlled, randomised double‐blind 24‐month intervention trial of MCFA supplementation within the AUstralian‐multidomain Approach to Reduce dementia Risk by prOtecting brain health With lifestyle intervention (AU‐ARROW) study, to investigate the additive effect of MCFA supplementation in older adults at increased risk of AD. A total of 124 participants will be recruited aged 60‐79 years, with subjective cognitive decline. Participants will be randomised 1:1 into either the intervention or placebo groups and will consume 3 daily doses at 15mL per dose of either MCFA or placebo supplement whilst continuing the AU‐ARROW protocol, which includes dietary education, physical activity, brain training, and health education. Result: The primary outcomes involve statistical assessment of cognition, blood ketone body levels, and brain glucose utilisation. At baseline, and every 6 months, participants will have fasting blood samples collected. At baseline, 12, and 24 months, participants will undergo cognitive assessments. At baseline and 24 months, participants will undergo fluorodeoxyglucose positron emission tomography scans to determine brain glucose utilisation. Conclusion: The final protocol is expected to maximise data collection and analyses. Combined with AU‐ARROW, it will allow for a) the implementation of MCFA supplementation guidelines in a plan to reduce cognitive decline and risk of AD, b) the determination of effects of MCFA consumption on neuroimaging and blood‐based biomarkers, and c) the comparison of between subject differences. [ABSTRACT FROM AUTHOR]