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- Title
Racial Disparity in Cerebrospinal Fluid Amyloid and Tau Biomarkers and Associated Cutoffs for Mild Cognitive Impairment.
- Authors
Garrett, Stephanie L.; McDaniel, Darius; Obideen, Malik; Trammell, Antoine R.; Shaw, Leslie M.; Goldstein, Felicia C.; Hajjar, Ihab
- Abstract
This case-control study compares cerebrospinal fluid (CSF) amyloid and tau biomarkers for Alzheimer disease in African American and white individuals with normal cognition and with mild cognitive impairment. Key Points: Question: Given the increased risk of Alzheimer disease in African American compared with white individuals, are there underlying racial differences in clinically used cerebrospinal fluid biomarkers? Findings: In this case-control study of 362 adults 50 years or older, African American participants with mild cognitive impairment had lower biomarker levels compared with white participants with mild cognitive impairment after adjusting for demographic characteristics. African American participants also had higher levels of β-amyloid 1-42 that were not significant after adjusting for demographic characteristics and cognitive performance, and diagnostic discrimination cutoffs were higher for β-amyloid 1-42 and lower for tau biomarkers in African American participants, except for the ratio of phosphorylated tau 181 to β-amyloid 1-42. Meaning: These findings suggest that race is an important factor when interpreting cerebrospinal fluid biomarkers, and the ratio of phosphorylated tau 181 to β-amyloid 1-42 may have less racial difference than other biomarkers. Importance: Prior evidence suggests that racial differences exist in tau biomarkers in mild cognitive impairment (MCI) and Alzheimer disease (AD). Whether this reported disparity is associated with a differential level of neurodegeneration and disease stage or with underlying mechanisms separate from amyloid or tau is unclear. Objectives: To compare cerebrospinal fluid (CSF) biomarkers in African American and white individuals with normal cognition and MCI, to estimate race-based cutoffs for these biomarkers that maximize diagnostic discrimination between normal cognition and MCI, and to study the association of demographic characteristics, cognitive performance, and common vascular risk factors with these differences. Design, Setting, and Participants: This case-control study conducted from March 1, 2016, through January 31, 2019, included participants in the Brain Stress Hypertension and Aging Research Program cohort undergoing baseline assessment. Participants were 50 years or older and recruited from the Atlanta, Georgia, area. Exposures: Self-reported race and cognitive status categorized using modified Petersen criteria and clinical consensus diagnosis. Main Outcomes and Measures: Levels of β-amyloid 1-42 (Aβ1-42), tau, and phosphorylated tau 181 (pTau181), the ratio of tau or pTau181 to Aβ1-42, and hippocampal volume on magnetic resonance imaging of the brain. Results: Data from 362 study participants were analyzed (mean [SD] age, 65.6 [7.9] years), of whom 152 (42.0%) were African American, 230 (63.5%) were women, and 189 (52.2%) had MCI. After adjustment for demographic characteristics and cognitive performance, lower mean (SE) levels were observed in African American vs white individuals with MCI for tau (52.40 [5.90] vs 78.98 [5.02] pg/mL; P =.001) and pTau181 (15.42 [2.06] vs 25.24 [1.75] pg/mL; P =.001) and a lower pTau181 to Aβ1-42 ratio (0.07 [0.02] vs 0.14 [0.01]; P =.003). There were no racial differences in the normal cognition group or in hippocampal volumes in the MCI group. Cutoffs for CSF biomarkers were higher for Aβ1-42 in African American relative to white individuals (208 [95% CI, 126-321] vs 197 [95% CI, 183-245] pg/mL) and lower for tau (51 [95% CI, 31-59] vs 59 [95% CI, 56-92] pg/mL) and pTau181 (12 [95% CI, 12-19] vs 20 [95% CI, 12-27] pg/mL) levels. Cutoffs for the pTau181 to Aβ1-42 ratio were 0.05 (95% CI, 0.03-0.12) for African American participants and 0.05 (95% CI, 0.05-0.13) for white participants. Conclusions and Relevance: This study found that African American individuals had lower levels of tau-based biomarkers that were not likely explained by the degree of disease stage or neurodegeneration reflected by hippocampal volumes. This study suggests that race is an important factor when interpreting CSF biomarkers, especially in the clinical diagnosis of prodromal AD. It appears that using the pTau181 to Aβ1-42 ratio may ameliorate these differences.
- Subjects
GEORGIA; BRAIN physiology; HIPPOCAMPUS physiology; AMYLOID; BIOMARKERS; BLACK people; CHI-squared test; CONFIDENCE intervals; MAGNETIC resonance imaging; NERVE tissue proteins; PSYCHOLOGICAL tests; QUESTIONNAIRES; RACE; REFERENCE values; RESEARCH funding; WHITE people; CASE-control method; RECEIVER operating characteristic curves; DATA analysis software; DESCRIPTIVE statistics
- Publication
JAMA Network Open, 2019, Vol 2, Issue 12, pe1917363
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2019.17363