Heat therapy in individuals at risk for Alzheimer's disease-methods for a randomized controlled trial.

Heat therapy (HT) has been shown to improve peripheral blood glucose regulation in some populations, yet its effects on brain glucose metabolism remain largely unexplored. The chronic benefits of HT may arise in part from upregulation of heat-shock proteins (HSPs). These proteins play a crucial role in the stress response and modulate diverse processes such as proteostasis and cell signaling pathways, including that of insulin signaling. Understanding the impact of HT on both peripheral and central glucose metabolism, including the effects of varying temperatures, is essential for elucidating potential mechanisms underlying its brain benefits. The Feasibility of Improving Glycemia to prevent Alzheimer's Disease (FIGHT-AD) study is a randomized controlled trial that aims to investigate changes in blood and brain glucose regulation following 10 weeks of HT. Specifically, we will examine the peripheral biomarker responses to warm and hot HT and assess how these responses relate to brain metabolic changes in both treatment groups. This trial will be the first to quantify the effect of HT on cerebral glucose metabolism in individuals at metabolic risk for Alzheimer's Disease (AD). The FIGHT-AD trial will provide critical data to inform the design of future clinical trials targeting metabolic and brain health through HT. Clinical trial registration: clinicaltrials.gov, identifier NCT06023407.