Two-year change in cognitive function is associated with changes in vascular function in a diverse cohort of middle-aged adults at-risk for Alzheimer's disease

Abstract

Introduction: The rate of Alzheimer's disease (AD) for Black Americans (BAs) is 64% higher than for non-Hispanic White Americans (NHWs). Vascular dysfunction may directly contribute to pathologies related to AD and cognitive decline. The purpose of this study is to examine relationships between vascular function and cognition over two years in a diverse cohort of middle-aged adults at-risk for AD. Methods: Cognitively unimpaired, middle-aged (45-65 years) adults with a parental history of AD were enrolled. Vascular function measures (flow-mediated dilation [FMD], EndoPat, pulse wave velocity [PWV], blood pressure [BP]) CSF markers of vascular function (ICAM-1, VCAM-1), and the Benson Complex Figure Test were collected at baseline and year 2. Linear regression analyses accounting for related covariates (age, gender, race, history of hypertension, and APOE ε4) were performed. Results: Participants (N=80) were mostly female (69%), well educated (81% ≥college), 48% ApoEε4 positive, and 34% B/AA. A higher proportion of B/AA had hypertension as compared to NHWs (57% vs 34%, p=.041). Central systolic BP, central mean arterial pressure, and EndoPat augmentation index were higher among BAs at baseline, while FMD was significantly lower at year 2. Increased CSF VCAM-1 was associated with lower FMD over 2 years. Changes in delayed Benson scores were significantly higher among NHWs (median change score 2, 95% CI 0.81-2.6) as compared to BAs (median change score 0, 95% CI -2.0-0.4) with a large effect size (Cohen's d=.823, p<.001). Decreasing scores from baseline to year 2 on the delayed Benson test were associated with increased PWV (β=-.383, p=.004), central mean arterial pressure (β=-.325, p=.011), and central systolic BP (β=-.344, p=.007). Discussion: Higher vascular stiffness and blood pressure were associated with a worsening measure of visuospatial ability, visual memory, and executive abilities over 2 years in a diverse cohort of middle-aged adults at-risk for AD. Worsening endothelial function was associated with higher CSF VCAM-1. Further, worsening measures of cognitive function and higher vascular risk factors were present among BAs. As midlife vascular risk factors are associated with late-life AD risk, these findings underscore the need to better understand mechanisms of vascular risk that could be targeted for risk reduction.