Elevated Aortic Stiffness is Associated with Weaker Executive Function in Individuals with Lower Cognitive Reserve via Reductions in Frontal Cerebrovascular Reserve

Abstract

IntroductionIndividuals with higher levels of formal education are hypothesized to tolerate greater brain pathology prior to the onset of cognitive decline via the ‘cognitive reserve’ (CR) hypothesis. Age‐related increases in aortic stiffness promotes the development of cerebrovascular dysfunction and independently predicts cognitive decline. However, the degree to which CR modulates relations between elevated aortic stiffness and cognitive performance is unknown. We hypothesized that 1) higher aortic stiffness (carotid‐femoral pulse wave velocity, cfPWV) and systolic blood pressure (BP) would be associated with weaker cognitive performance in middle‐aged/older (MA/O) adults with lower but not higher CR; and 2) elevated cfPWV would be associated with reduced regional cerebral blood flow (CBF) and cerebrovascular reserve (CVR), or the ability to augment CBF in response to a physiological or pharmacological stimulus, in a subset of MA/O adults.Methods/ResultsOne hundred and thirty‐five MA/O (age 67.3 ± 0.7 yrs; range 55–85 yrs) adults were recruited. CR status was categorized by years of formal education as ‘lower’ (≤12 yrs, n=39) or ‘higher’ (>12 yrs, n=96). MA/O adults with lower CR performed weaker on global cognitive function (RBANS Total Scale, 95.1 ± 12.6 vs. 104.5 ± 12.2, p<0.001) and processing speed (Stroop Word Reading, 84.7 ± 2.2 vs. 91.2 ± 1.7, p=0.02) tasks compared with higher CR, but did not differ on executive function (Stroop Interference (33.4 ± 1.1 vs. 34.5 ± 0.8, p=0.38). Age, circulating lipids, BMI and BP did not differ between groups (all p>0.05). The following partial correlations were adjusted for age, sex, education, medications and mean arterial pressure (MAP, cfPWV only). Consistent with our hypothesis, weaker executive function was associated with elevated cfPWV (r= −0.45, p=0.017), central systolic BP (r= −0.46, p=0.038) and central pulse pressure (r= −0.47, p=0.032) in individuals with lower but not higher CR. Slower processing speed was related to greater central systolic BP (r= −0.44, p=0.047) in the lower CR group only. Finally, higher brachial systolic BP was associated with weaker executive function in both the lower (r= −0.43, p=0.02) and higher (r= −0.34, p= 0.004) CR groups. In a subset of these MA/O adults (n=24, age 70 ± 2.0 yrs), regional frontal CBF and CVR were measured using the ‘gold−standard’ [15O]Water PET imaging based on the frontal region's role in executive functioning. Elevated cfPWV was associated with reduced frontal CVR (r= −0.49, p=0.034) but not frontal CBF, after adjustment for age, sex and MAP and remained associated after adjustment for years of education (r= −0.50, p=0.034) or CR group (r= −0.47, p=0.049). Brachial systolic BP was not associated with frontal CVR or CBF.ConclusionMA/O adults with lower CR may be more sensitive to the adverse effects of age‐related increases in cfPWV on executive function tasks compared with MA/O adults with higher CR. Furthermore, age‐related increases in cfPWV may impair the ability of the cerebrovasculature to augment CBF to the frontal lobe resulting in reductions in executive function with aging.Support or Funding InformationNIH 5R01 AG03417, R03 AG047306‐01, 1R21 AG043722, CTSA U54TR001356This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.