Heat therapy: possible benefits for cognitive function and the aging brain.

AD is the most common neurodegenerative disease, yet there are no disease-modifying treatments available and there is no cure. It is becoming apparent that metabolic and vascular conditions such as Type 2 diabetes (T2D) and hypertension promote the development and accumulation of Alzheimer's Disease-Related Dementia pathologies. To this end, aerobic exercise, which is a common lifestyle intervention for both metabolic disease and hypertension, is shown to improve brain health during both healthy aging and dementia. However, noncompliance or other barriers to exercise response are common in exercise treatment paradigms. In addition, reduced intracellular proteostasis and mitochondrial function could contribute to the etiology of AD. Specifically, compromised chaperone systems (i.e. heat shock protein [HSPs] systems) can contribute to protein aggregates (i.e. beta-amyloid plaques and neurofibrillary tangles) and reduced mitochondrial quality control (i.e. mitophagy). Therefore, novel therapies that target whole-body metabolism, the vasculature, and chaperone systems (like HSPs) are needed to effectively treat AD. This review focuses on the role of heat therapy in the treatment and prevention of AD. Heat therapy has been independently shown to reduce whole-body insulin resistance, improve vascular function, activate inter-organ crosstalk via endocytic vesicles, and activate HSPs to improve mitochondrial function and proteostasis in a variety of tissues. Thus, heat therapy could offer immense clinical benefit to patients suffering from AD. Importantly, future studies in patients are needed to determine the safety and efficacy of heat therapy in preventing AD.