Baseline Results: The Association Between Cardiovascular Risk and Preclinical Alzheimer's Disease Pathology (ASCEND)
Veena V Kumar1, Hanfeng Huang2, Liping Zhao2
1Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
Insights
African Americans (AAs) show poorer vascular health and cognition compared to Whites, with race influencing the link between tau biomarkers and cognitive decline in Alzheimer's disease (AD) risk.
Area of Science:
- Neuroscience
- Cardiovascular Health
- Racial Health Disparities
Background:
- Alzheimer's Disease (AD) affects African Americans (AAs) at a higher rate than non-Hispanic White Americans (Whites).
- Poor vascular function, genetics, stress, and inflammation are hypothesized contributors to AD pathology, potentially disproportionately impacting AAs.
Purpose of the Study:
- To investigate racial differences in AD biomarkers within the cerebrospinal fluid (CSF).
- To examine the relationship between peripheral vascular dysfunction, cognition, and CSF AD biomarkers.
- To determine if these relationships vary by race in a high-risk cohort.
Main Methods:
- Enrolled 82 cognitively normal, middle-aged adults (≥45 years) of AA and White race with a parental history of AD.
- Collected cerebrospinal fluid (CSF) via lumbar puncture.
- Performed vascular ultrasound and cognitive testing.
Main Results:
- AAs exhibited poorer preclinical vascular health (higher SBP, MAP, arterial stiffness) but lower CSF tau burden than Whites.
- Race significantly modified the association between total tau, phospho-tau, and executive function (Trails B).
- Smaller variations in tau correlated with poorer cognition in AAs compared to Whites.
Conclusions:
- In a high-risk cohort, AAs presented with worse peripheral vascular health and cognition than Whites.
- Despite lower overall tau burden, race altered the tau-cognition relationship, indicating that subtle tau differences are linked to worse cognitive function in AAs.
Background:
The rate of AD for African Americans (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.
Objective:
Our objective was to determine if in a healthy middle-aged cohort at risk for AD (1) AD biomarkers in CSF differ by race, (2) peripheral vascular dysfunction and cognition are related to a higher burden of CSF AD biomarkers, and (3) these relationships differ by race.
Methods:
We enrolled 82 cognitively normal, middle-aged (45 and older) adults including AAs and Whites at high risk for AD due to parental history. Study procedures included lumbar puncture, vascular ultrasound, and cognitive testing.
Results:
While participants were in overall good health, AAs exhibited poorer indices of preclinical vascular health, including higher central SBP, central MAP, and EndoPAT AI, a marker of arterial stiffness. AAs also had significantly less cerebrospinal fluid tau burden than Whites. After polynomial regression analysis, adjusted for age, gender, education, and ApoE4 status, 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.
Conclusion:
In a healthy middle-aged cohort at risk for AD, AAs had worse peripheral vascular health and worse cognition than Whites. Despite lower tau burden overall, race modified the relationship between tau and cognition, such that small differences in tau between AAs was related to worse cognition when compared to Whites.
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