Home-based heat therapy reduces plasma pTau-181 in post-menopausal women with hypertension

Post-menopausal women with hypertension are at an increased risk for developing Alzheimer’s disease and related dementias (ADRD). Exercise training has been reported to lower risk of ADRD long term, but adherence is often low in this population. Interestingly, heat therapy reduces ADRD risk in middle-aged men, but its efficacy in post-menopausal women remains unclear. Therefore, we tested the hypothesis that compared with sham, home-based heat therapy would reduce blood-based biomarkers of ADRD risk in post-menopausal women with hypertension. Forty-seven women with normal cognitive function were randomly assigned to sham ( N = 24, 69 ± 5 y, daytime systolic blood pressure 141 ± 6 mmHg) or heat therapy ( N = 23, 70 ± 6 y, daytime systolic blood pressure 141 ± 6 mmHg). Participants in the heat therapy group immersed their lower legs (~33 cm) in a circulated water bath set to 42 °C, whereas water temperature for the sham group was set to 35 °C. All participants were instructed to immerse their legs for 45 mins, 4 times per week for 8 weeks. Blood plasma was analyzed for amyloid ß-42, amyloid ß-40, neurofilament light, tau, and phosphorylated tau-181 (p-tau181) using the ultrasensitive single molecule array assay. Amyloid ß-42 ( P = 0.5), amyloid ß-40 ( P = 0.8), neurofilament light ( P = 0.6), and tau ( P = 0.8) did not differ across time or between groups. However, p-tau181 was reduced following 8-weeks of heat therapy (pre, 23.4 ± 6.1 pg ml -1 vs. post, 20.8 ± 6.1 pg ml -1 ; P = 0.01), whereas there was no change across time for the sham group (pre, 22.9 ± 5.8 pg ml -1 vs. post, 25.3 ± 11.3 pg ml -1 ; P = 0.3). Notably, adherence was 97% across both interventions. Plasma p-tau181 is increased with pre-clinical Alzheimer’s disease and further increases with mild cognitive impairment and dementia. In addition, it is strongly correlated with cerebral spinal fluid concentrations and tau-positive brain imaging. As such, plasma p-tau181 is an emerging biomarker of the progression of cognitive impairment associated with Alzheimer’s disease. Thus, the reduction in p-tau181 following heat therapy suggests that home-based heat therapy may attenuate ADRD risk in post-menopausal women with hypertension. FUNDING SOURCE: This work was supported by grants from the National Institutes of Health (T32 AG020494; R01AG059314; F32HL167556). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.