Passive heat therapy improves cognitive and cerebrovascular function in healthy midlife and older adults

Fluid cognitive function (the domain of cognition most impaired in Alzheimer’s Disease) declines with aging, predisposing older adults to Alzheimer’s Disease and related dementias. Age-related cerebrovascular dysfunction contributes to cognitive decline by impairing brain blood flow such that there is chronic cerebral hypoperfusion, which has been linked to cognitive impairment. Increased oxidative stress and the resultant loss of nitric oxide (NO) bioavailability likely play mechanistic roles in age-related cerebrovascular dysfunction. Passive heat therapy (i.e., regular heat exposure) improves peripheral vascular outcomes and reduces oxidative stress and, therefore, may also improve cognitive and cerebrovascular function. Purpose: To test the hypotheses that heat therapy would 1) improve fluid cognitive function, 2) increase total cerebral blood flow (tCBF), and 3) reduce cerebrovascular reactive oxygen species (ROS) production and increase NO bioavailability. Methods and results: Midlife and older (ML/O) adults (50+ years) were randomized to 8-10 weeks of passive heat therapy (via hot [40 °C] water immersion; 30 x 60-min sessions) or sham control (via thermoneutral [36 °C] water immersion; NCT03264508). The following preliminary results were collected at baseline (pre) and at the end (post) of the heat therapy or sham intervention (n=6-10/group). Fluid Cognition Composite scores, assessed using the NIH Toolbox Cognition Battery, increased from 97± 3 (mean ± SEM) at baseline to 100± 3 at end-intervention (p=0.03) in subjects who underwent heat therapy, an improvement from the 42nd to 50th percentile of all U.S. adults, but there was no consistent change in sham subjects (p=0.16). tCBF, assessed via duplex ultrasonography of the vertebral and internal carotid arteries, increased from 766± 99 mL/min at baseline to 841± 123 mL/min after heat therapy (p=0.03), whereas there was no change following sham (pre: 723± 20 vs. post: 729± 26 mL/min; p=0.89). Cerebrovascular ROS production and NO bioavailability were assessed with fluorescent probes in vitro using human brain endothelial cells (HBECs; technical replicates n=24-29) cultured in hot (39 °C; to match in vivo body core temperature during heat therapy sessions) and standard (37 °C) conditions. HBECs cultured in hot conditions had lower basal ROS production (hot: 860± 7 AU vs. standard: 907± 5 AU; p<0.01) and higher acetylcholine-stimulated NO production (hot: 1.5± 0.06 vs. standard: 1.3± 0.04 fold change in NO production; p=0.03). Conclusions: These results suggest that heat therapy can improve fluid cognition and brain blood flow in ML/O adults, possibly by reducing brain endothelial cell ROS production and increasing NO bioavailability. Heat therapy shows potential to protect cognitive performance in the domain most affected by Alzheimer’s Disease and improve cerebrovascular function in ML/O adults. NIH/NCATS UL1 TR002535; T32 AG000279; R01 AG073117 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.