RACE MODIFIES THE RELATIONSHIP BETWEEN ALZHEIMER’S DISEASE (AD) BIOMARKERS AND COGNITION IN A COHORT OF MIDDLE-AGED INDIVIDUALS AT HIGH-RISK FOR AD

Abstract

The rate of AD for African American's (AAs) is 64% higher than for non-Hispanic White Americans (Whites). It is hypothesized that poor peripheral vascular function, in combination with genetics, stress and inflammation may directly contribute to the accumulation of AD pathologic biomarkers. These risk factors may disproportionately affect AAs. We hypothesized that AD biomarkers in CSF differ by race, that peripheral vascular dysfunction and cognition are related to higher burden of CSF AD biomarkers, and that these relationships differ by race. The Association between Cardiovascular Risk and Preclinical Alzheimer's Disease Pathology (ASCEND) Study is a longitudinal, two-year observational study which enrolled 82 cognitively normal, middle-aged (45 and older) adults including AAs and Whites at high risk for AD due to parental history. Here, we present results of baseline data. Study procedures included lumbar puncture for CSF collection, peripheral vascular ultrasound and cognitive testing. 30 AAs and 50 Whites were enrolled. Participants were middle aged (60.1 ± 7.8yrs and 58.5 ± 6.1yrs in Whites and AAs, respectively). 83.3% of AAs were female compared to 56.0% of Whites. AAs performed more poorly on all cognitive tests, though participants were all cognitively normal. While participants were in overall good health (systolic blood pressure (SBP) 127.6 ± 13.3bpm in AAs and 125.1 ± 12.3bpm in Whites), AAs exhibited poorer indices of preclinical vascular health, including higher central SBP, central mean arterial pressure (MAP), and EndoPAT AI, a marker of arterial stiffness. Finally, AAs had significantly less CSF tau burden than Whites. After polynomial regression analysis, adjusted for age, gender, education, and ApoE4 status, we found that race significantly modified the relationship between total tau, phospho-tau and Trails b, a marker of executive function. Small differences in tau correlated with poorer cognition in AAs when compared to Whites (Figure 1, 2, and 3).