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Article
February 10, 2021

Amyloid PET Imaging in Self-Identified Non-Hispanic Black Participants of the Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) Study

March 16, 2021 issue
96 (11) e1491-e1500

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.

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Information & Authors

Information

Published In

Neurology®
Volume 96Number 11March 16, 2021
Pages: e1491-e1500
PubMed: 33568538

Publication History

Received: August 4, 2020
Accepted: December 7, 2020
Published online: February 10, 2021
Published in print: March 16, 2021

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Disclosure

R.A. Sperling receives research funding from Eli Lilly and Janssen and has served as a paid consultant to AC Immune, Biogen, Janssen, and Neurocentria. E.C. Mormino has served as a paid consultant to Roche, Genentech, Eli Lilly, and Alector. The remaining authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Study Funding

The Alzheimer's Association (AARFD-18-562691 [K.D. Deters]), Stanford Aging and Ethnogeriatrics (SAGE 1227707-711-WAKTZ [K.D. Deters]), and K01 AG051718 (E.C. Mormino).

Authors

Affiliations & Disclosures

Kacie D. Deters, PhD
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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Valerio Napolioni, PhD
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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Reisa A. Sperling, MD
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.
Disclosure
Scientific Advisory Boards:
1.
(1) Commercial - AC Immune
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) Commercial - GE Healthcare, travel, honorarium, (2) Commercial - Insightec, travel, honorarium
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Personal: 1) Biogen, commercial 2) Roche, commercial, 3) AC Immune, commercial, 4) Eisai, commercial, 5) Takeda, commercial 6) Neurocentria, commercial 7) Janssen, commercial 8) Cytox, commercial 9) Prothena, commercial 10) Acumen, commercial 11) JOMDD, commercial 12) Renew, commercial 13) Alnylam, commercial 14) Neuraly, commercial Spouse: 1) Novartis, commercial 2) AC Immune, commercial 3) Janssen, commercial 4) Cerveau, commercial
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Eli Lilly- clinical trial support 2014-present Eisai - clinical trial support 2020-present
Research Support, Government Entities:
1.
(1) R01 AG063689, co-principal investigator, 2019-2024, (2) U24AG057437, co- principal investigator, 2017-2022, (3) P01AG036694, co-principal investigator, 2010-2025
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Alzheimer's Association, co-principal investigator, 2016-2023
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Michael D. Greicius, MD
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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
Co-founder and shareholder in SBGneuro a company that does imaging data analysis for academic and commercial research studies.
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH RO1
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Richard Mayeux, MD
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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Consultant to the Alzheimer's Disease Center at Rush University Medical School
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
AG054023 Genetic Epidemiology of Cerebrovascular Factors in Alzheimer's Disease
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Timothy Hohman, PhD
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.
Disclosure
Scientific Advisory Boards:
1.
Serve on advisory board for Vivid Genomics
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) NIH/NIA, K01 AG049164, PI, 4/1/16-3/31/21 (2) NIH/NICHD, K12 HD043483, Scholar, 2/1/15-3/31/16 (3) NIH/NIA, R01 AG059716, PI, 9/15/18-9/14/23 (4) NIH/NIA, R21 AG059941, PI, 9/1/18-8/31/20 (5) NIH/NIA, Contract HHSN311201600276P, PI, 9/1/16- 8/31/19 (6) NIH/NIA, R01 AG061518, PI, 3/15/19-12/31/23 (7) NIH/NIA, P20 AG068082, Biomarker Core PI, 8/15/20- 7/31/23
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Elizabeth C. Mormino, PhD
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.
Disclosure
Scientific Advisory Boards:
1.
Eli Lilly, Roche
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Consultant Alector
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Funding Source: NIH/NIA Grant number: K01AG051718 Role: PI Years: 5/2016-current Funding Source: NIH/NIA Grant number: R21AG058859 Role: PI Years: 3/2018-current
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence Dr. Deters [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

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  9. Protective effects of sleep duration and physical activity on cognitive performance are influenced by β-amyloid and brain volume but not tau burden among cognitively unimpaired older adults, NeuroImage: Clinical, 39, (103460), (2023).https://doi.org/10.1016/j.nicl.2023.103460
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  10. Biomarkers of Alzheimer’s disease in Black and/or African American Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants, Neurobiology of Aging, 131, (144-152), (2023).https://doi.org/10.1016/j.neurobiolaging.2023.07.021
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