The association between cardiovagal baroreceptor sensitivity and brain mechanical properties across the lifespan

High blood pressure (BP) and BP variability are risk factors for cognitive decline and dementia, making mechanisms of BP regulation interesting targets to attenuate age-related cognitive decline. The cardiovagal baroreflex is essential in the beat-to-beat regulation of BP, and the responsiveness of this reflex, known as cardiovagal baroreceptor sensitivity (cBRS), is a common measure of cardiac autonomic function. cBRS declines (worsens) with age, and lower cBRS is associated with worse white matter integrity and cerebral perfusion and a higher risk of Alzheimer’s disease. However, no studies have investigated the association of cBRS with brain mechanical properties assessed by magnetic resonance elastography (MRE). OBJECTIVES: To investigate differences in cBRS and brain mechanics assessed by MRE across the lifespan and whether cBRS is associated with whole brain stiffness and damping ratio (DR). We hypothesized that cBRS and brain mechanics would worsen with age and that higher (better) cBRS would be associated with better brain mechanics. METHODS: Young (n=10, 3 men, 22-29 years), midlife (n=22, 11 men, 51-63 years), and older adults (n=14, 4 men, 66-79 years) underwent supine resting electrocardiography and finger photoplethysmography. cBRS was determined using the sequence method for all sequences (cBRSall), which included up sequences (systolic BP and R-R interval increase) and down sequences (systolic BP and R-R interval decrease). MRE was used to assess whole brain stiffness and DR. We used one-way ANOVA models with Bonferroni post-hoc comparisons to assess differences in cBRS and brain mechanics across the three age groups. We performed regression analyses with robust standard errors (HC3) to assess the relation of cBRSall with brain stiffness and DR, controlling for age. Data are presented as mean ± standard deviation. RESULTS: cBRSall was higher (better) in young adults (32.6 ± 13.3 ms/mmHg), compared to midlife (10.1 ± 3.8 ms/mmHg, p< 0.01) and older adults (11.8 ± 5.7 ms/mmHg, p< 0.01) with no differences between midlife and older adults (p=1.00). Brain stiffness was lower (worse) in older adults (2.56 ± 0.12 kPa) compared to young (2.89 ± 0.13 kPa, p< 0.01) and midlife adults (2.80 ± 0.15 kPa, p< 0.01) with no differences between young and midlife adults (p=0.25). Similarly, DR was higher (worse) in older adults (0.27 ± 0.01) compared to young (0.25 ± 0.01, p< 0.01) and midlife adults (0.26 ± 0.01, p=0.01) with no differences between young and midlife adults (p=0.64). Age was negatively correlated with brain stiffness (b=-0.0099, t=-4.68, p< 0.01), while cBRSall showed a marginal negative effect on brain stiffness (b=-0.0059, t=-1.98, p=0.054). Similarly, age was positively correlated with DR (b=0.0004, t=2.93, p< 0.01), while cBRSall was not a significant predictor of DR (p=0.18). CONCLUSION: cBRS and brain mechanics were strongly associated with age, but cBRS was not associated with better brain mechanics as hypothesized. This may be because cBRS but not brain mechanics were different between young and midlife adults, while brain mechanics but not cBRS were different between midlife and older adults. This suggests that cBRS may decline earlier in life than changes in brain mechanics, making it difficult to demonstrate an association in a cross-sectional cohort. Additional work is needed to determine the precise age ranges during which changes in autonomic function and brain mechanics occur, and future studies should utilize longitudinal designs to investigate whether cBRS and other vascular factors at younger ages have a causal impact on brain health later in life. Supported by NIH grants, R01AG080052, P20GM113125, & P30GM145765, & AHA 24IAUST1199297. This abstract was presented at the American Physiology Summit 2026 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.