Kacie D Deters1, Valerio Napolioni2, Reisa A Sperling2, Michael D Greicius2, Richard Mayeux2, Timothy Hohman2, Elizabeth C Mormino2. 1. From the Department of Neurology and Neurological Sciences (K.D.D., V.N., M.D.G., E.C.M.), Stanford University School of Medicine, Palo Alto, CA; Department of Neurology (R.A.S.), Brigham and Women's Hospital, Massachusetts General Hospital, Boston; Department of Neurology, The Taub Institute for Research on Alzheimer's Disease and The Aging Brain, and The Institute for Genomic Medicine (R.M.), Columbia University Medical Center and The New York Presbyterian Hospital, New York; and Vanderbilt Memory and Alzheimer's Center and Vanderbilt Genetics Institute (T.H.), Nashville, TN. kdeters@stanford.edu. 2. From the Department of Neurology and Neurological Sciences (K.D.D., V.N., M.D.G., E.C.M.), Stanford University School of Medicine, Palo Alto, CA; Department of Neurology (R.A.S.), Brigham and Women's Hospital, Massachusetts General Hospital, Boston; Department of Neurology, The Taub Institute for Research on Alzheimer's Disease and The Aging Brain, and The Institute for Genomic Medicine (R.M.), Columbia University Medical Center and The New York Presbyterian Hospital, New York; and Vanderbilt Memory and Alzheimer's Center and Vanderbilt Genetics Institute (T.H.), Nashville, TN.
Abstract
OBJECTIVE: To examine whether amyloid PET in cognitively normal (CN) individuals screened for the Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) study differed across self-identified non-Hispanic White and Black (NHW and NHB) groups. METHODS: We examined 3,689 NHW and 144 NHB participants who passed initial screening for the A4 study and underwent amyloid PET. The effect of race on amyloid PET was examined using logistic (dichotomous groups) and linear (continuous values) regression controlling for age, sex, and number of APOE ε4 and APOE ε2 alleles. Associations between amyloid and genetically determined ancestry (reflecting African, South Asian, East Asian, American, and European populations) were tested within the NHB group. Potential interactions with APOE were assessed. RESULTS: NHB participants had lower rates of amyloid positivity and lower continuous amyloid levels compared to NHW participants. This race effect on amyloid was strongest in the APOE ε4 group. Within NHB participants, those with a lower percentage of African ancestry had higher amyloid. A greater proportion of NHB participants did not pass initial screening compared to NHW participants, suggesting potential sources of bias related to race in the A4 PET data. CONCLUSION: Reduced amyloid was observed in self-identified NHB participants who passed initial eligibility criteria for the A4 study. This work stresses the importance of investigating AD biomarkers in ancestrally diverse samples as well as the need for careful consideration regarding study eligibility criteria in AD prevention trials.
OBJECTIVE: To examine whether amyloid PET in cognitively normal (CN) individuals screened for the Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) study differed across self-identified non-Hispanic White and Black (NHW and NHB) groups. METHODS: We examined 3,689 NHW and 144 NHB participants who passed initial screening for the A4 study and underwent amyloid PET. The effect of race on amyloid PET was examined using logistic (dichotomous groups) and linear (continuous values) regression controlling for age, sex, and number of APOE ε4 and APOE ε2 alleles. Associations between amyloid and genetically determined ancestry (reflecting African, South Asian, East Asian, American, and European populations) were tested within the NHB group. Potential interactions with APOE were assessed. RESULTS: NHB participants had lower rates of amyloid positivity and lower continuous amyloid levels compared to NHW participants. This race effect on amyloid was strongest in the APOE ε4 group. Within NHB participants, those with a lower percentage of African ancestry had higher amyloid. A greater proportion of NHB participants did not pass initial screening compared to NHW participants, suggesting potential sources of bias related to race in the A4 PET data. CONCLUSION: Reduced amyloid was observed in self-identified NHB participants who passed initial eligibility criteria for the A4 study. This work stresses the importance of investigating AD biomarkers in ancestrally diverse samples as well as the need for careful consideration regarding study eligibility criteria in AD prevention trials.
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