Elevated Aortic Stiffness is Associated with Lower Brain pH and Executive Function Performance in Middle‐aged and Older Adults

Abstract

IntroductionElevated aortic stiffness and pulse pressure (PP) are risk factors for development of mild cognitive impairment (MCI) and Alzheimer's disease (AD) mediated in part by the development of cerebrovascular dysfunction. Cerebrovascular dysfunction uncouples cerebral blood flow (CBF) supply from metabolic demand, contributing in part to cerebral hypoperfusion, acidosis and cognitive decline in AD. Brain T1rho is a novel pH‐sensitive magnetic resonance imaging (MRI) biomarker that is increased in patients with MCI and AD compared with healthy controls (HC). T1rho measures the change in T1 relaxation time in the rotating frame with greater T1rho values (i.e., longer relaxation time) associated with a more acidic pH. However, the degree to which higher T1rho signal (i.e., lower brain pH = more acidic) is associated with 1) lower cognitive performance; 2) higher brachial PP and 3) elevated aortic stiffness in middle‐aged/older (MA/O) adults is unknown.Methods/ResultsTwenty‐seven MA/O adults (mean ± SE: 71.8 ± 2.1 years, range: 50–90 years) were recruited to undergo clinic blood pressure (BP), neuropsychological, MRI (structural and T1rho) testing and vascular testing (subset only). Executive function and delayed memory performance were measured using the Trailmaking test (TMT) A & B and Rey Auditory Verbal Learning Test, respectively. In agreement with prior studies, global T1rho signal was elevated in individuals with cognitive impairment (MCI or early AD, n=10) compared with HC (90.7 ± 3.1 vs. 81.8 ± 1.2 ms, p= 0.004). Consistent with our hypothesis, higher T1rho signal was associated with greater time to completion on the TMT B (r = 0.44, p = 0.026), TMT B‐A (r = 0.39, p = 0.047) and lower delayed memory performance (r = −0.48, p = 0.012, all adjusted for age) in the entire cohort. However, T1rho was not related to PP (r = 0.38, p= 0.069) and remained unassociated after adjusting for age (p=0.80). In the subset of MA/O adults with T1rho (n = 15; 70.0 ± 2.0 years, HC, n= 21, MCI, n=2), greater aortic stiffness (carotid‐femoral pulse wave velocity, cfPWV) was associated with higher T1rho signal (r= 0.58, p= 0.039, adjusted for mean arterial pressure). Furthermore, cfPWV was associated with slower TMT B (r = 0.45, p = 0.034) but not TMT B‐A (r = 0.46, p = 0.066) or delayed memory performance (p= 0.77, all adjusted for mean arterial pressure). Additional adjustment for age abolished (p > 0.05) the relation between cfPWV and TMT performance and T1rho signal in the present cohort.ConclusionThese preliminary data indicate that the age‐related increase in aortic stiffness is associated with lower executive function performance on the TMT task and higher T1rho signal, consistent with lower brain pH, in MA/O adults. More studies are needed to determine the mechanism by which elevated aortic stiffness contributes in part to decreased brain pH and how brain pH may potentially modulate reduced executive function with aging.Support or Funding InformationBiological Sciences Funding Program, Office of Vice President for Research, University of Iowa and NIH 1R03AG047306This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.