J Appl Physiol 138: 720–730, 2025. First published January 20, 2025; doi:10.1152/japplphysiol.00396.2024
RESEARCH ARTICLE
Improving glycemic control via heat therapy in older adults at risk for Alzheimer’s disease (FIGHT-AD): a pilot study Anneka E. Blankenship,1,2 Riley Kemna,1,2 Paul J. Kueck,1,2 Casey John,1,2 Michelle Vitztum,3 Lauren Yoksh,4 Jonathan D. Mahnken,1,4,5 Eric D. Vidoni,1,2 Jill K. Morris,1,2 and Paige C. Geiger1,6 1
University of Kansas Alzheimer’s Disease Research Center, University of Kansas Medical Center, Fairway, Kansas, United States; 2Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, United States; 3KU Diabetes Institute, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States; 4 Department of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, Kansas, United States; 5 Frontiers Clinical and Translational Science Institute, University of Kansas Medical Center, Kansas City, Kansas, United States; and 6Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States
Abstract Impaired glycemic control increases the risk of type 2 diabetes (T2D) and Alzheimer’s disease (AD). Heat therapy (HT), via hot water immersion (HWI), has shown promise in improving shared mechanisms implicated in both T2D and AD, like blood glucose regulation, insulin sensitivity, and inflammation. The potential for HT to improve brain health in individuals at risk for AD has not been examined. This pilot study aimed to assess the feasibility and adherence of using HT in cognitively healthy older individuals at risk for AD due to existing metabolic risk factors. Participants underwent 4 wk of HT (three sessions/week) via HWI, alongside cognitive screening, self-reported sleep characterization, glucose tolerance tests, and MRI scans pre- and postintervention. A total of 18 participants (9 males, 9 females; mean age: 71.1 ± 3.9 yr), demonstrating metabolic risk, completed the intervention. Participant adherence for the study was 96% (8 missed sessions out of 216 total sessions), with one study-related mild adverse event (mild dizziness/nausea). Overall, the research participants responded to a postintervention survey saying they enjoyed participating in the study and it was not a burden on their schedules. Secondary outcomes of the HT intervention demonstrated significant changes in mean arterial pressure, diastolic blood pressure, and cerebral blood flow (P < 0.05), with a trend toward improved body mass index (P ¼ 0.06). Future studies, including longer durations and a thermoneutral control group, are needed to fully understand heat therapy’s impact on glucose homeostasis and the potential to improve brain health. NEW & NOTEWORTHY Our pilot study demonstrated promising results for heat therapy (HT) via hot water immersion in older adults at risk for Alzheimer’s disease due to metabolic factors. Despite a relatively short intervention, significant improvements in mean arterial pressure, diastolic blood pressure, and cerebral blood flow postintervention were observed. High participant adherence, overall satisfaction, and minimal adverse events suggest HT’s feasibility. These findings highlight HT’s potential as an effective alternative intervention for cardiometabolic dysfunction in at-risk populations. Alzheimer’s disease; glucose metabolism; heat therapy; hot water immersion; metabolic dysfunction
INTRODUCTION Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and by 2060, the number of affected individuals is predicted to reach 13.8 million worldwide (1). Although the etiology of AD is not fully understood, mechanisms such as impaired energy metabolism, cellular bioenergetic dysfunction, reduced intracellular protein homoeostasis, and inflammation are all potential contributors (2–6). The link between metabolic dysfunctions and AD (7), particularly impaired glucose metabolism (8), suggests a critical intersection between metabolic health and neurodegenerative disease progression.
Elevated glucose levels, for example, correlate with increased cerebral amyloid deposition—a hallmark of AD—and reduced amyloid b (Ab) catabolism, indicating that interventions targeting metabolic health could play a crucial role in managing AD risk (9–13). A recently completed exercise prevention trial in cognitively healthy older adults at risk for AD showed that longitudinal increases in fasting glucose over one year were associated with regional increases in brain amyloid (10). This research suggests that glucose regulation may be an important therapeutic target for AD. Traditional lifestyle interventions for AD focus on symptom management and slowing disease progression. Aerobic
Correspondence: P. C. Geiger (pgeiger@kumc.edu). Submitted 28 May 2024 / Revised 26 June 2024 / Accepted 9 January 2025 720
8750-7587/25 Copyright © 2025 The Authors. Licensed under Creative Commons Attribution CC-BY 4.0. Published by the American Physiological Society.
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