@article{177750ea2b564ba5b4b6dfd721d34603,
title = "Amyloid-Related Imaging Abnormalities and Other MRI Findings in a Cognitively Unimpaired Population With and Without Cerebral Amyloid",
abstract = "Background: Screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer{\textquoteright}s Disease (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies provide a unique opportunity to compare magnetic resonance imaging (MRI) findings such as amyloid-related imaging abnormalities (ARIA) in cognitively unimpaired elderly with and without elevated cerebral amyloid. Objectives: To compare screening MRI findings, such as ARIA, in the cognitively unimpaired potential participants of a clinical trial with and without elevated cerebral amyloid. Design: Cross-sectional analysis of structural MRI findings in screening data from the A4 and LEARN studies. Setting: The A4 Study is a multi-center international clinical trial. The LEARN Study is a multi center observational study in the United States. Participants: Clinically normal older adults (65–85 years) with elevated cerebral amyloid (Aβ+; n = 1250, A4) and without elevated cerebral amyloid (Aβ-; n = 538, LEARN). Measurements: Participants underwent florbetapir positron emission tomography for Aβ+/- classification. A centrally read 3T MRI to assess for study eligibility was conducted on study qualified MRI scanners. Results: No ARIA-effusions (ARIA-E) was detected on screening MRI in the Aβ+ or Aβ- cohorts. At least one ARIA-H (microhemorrhages [MCH] or superficial siderosis [SS]) was present in 18% of the Aβ+ cohort compared with 8% in Aβ- (P < 0.001). In the Aβ+ cohort, approximately 2% of screening MRIs demonstrated MCH ≥4 compared with 0% in Aβ-. The presence of two apolipoprotein E ε4 (APOEε4) alleles (vs no ε4 alleles) in the Aβ+ cohort increased the odds for presence of MCH (odds ratio [OR] = 2.03; 95% CI, 1.23 to 3.27, P = 0.004). Cortical infarctions (4% vs 0%) and subcortical infarctions (10% vs 1%) were observed at statistically significantly higher prevalence in the Aβ+ cohort compared with Aβ- (P < 0.001). Females showed reduced odds of MCH in the Aβ+ cohort by a factor of 0.63 (95% CI, 0.47 to 0.84, P = 0.002). Conclusions: ARIA-E is rare in cognitively unimpaired Aβ+ and Aβ- populations prior to anti-amyloid drug intervention. ARIA-H in Aβ+ was greater than in Aβ- populations.",
keywords = "Amyloid-related imaging abnormalities, florbetapir positron emission tomography, magnetic resonance imaging, preclinical Alzheimer{\textquoteright}s disease",
author = "{A4 Study Team} and Roy Yaari and Holdridge, {K. C.} and J. Choi and Donohue, {M. C.} and K. Kantarci and Jack, {C. R.} and Zuk, {S. M.} and Sims, {J. R.} and Johnson, {K. A.} and Aisen, {P. S.} and Sperling, {R. A.}",
note = "Funding Information: Funding: The A4 Study is a secondary prevention trial in preclinical Alzheimer{\textquoteright}s disease, aiming to slow cognitive decline associated with brain amyloid accumulation in clinically normal older individuals. The A4 Study is funded by a public private philanthropic partnership, including funding from the National Institutes of Health-National Institute on Aging (U19AG010483; R01AG063689), Eli Lilly and Company, Alzheimer{\textquoteright}s Association, Accelerating Medicines Partnership, GHR Foundation, an anonymous foundation, and additional private donors, with in-kind support from Avid, Cogstate, Albert Einstein College of Medicine, US Against Alzheimer{\textquoteright}s Disease, and Foundation for Neurologic Diseases. The companion observational Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study is funded by the Alzheimer{\textquoteright}s Association and GHR Foundation. The A4 and LEARN studies are led by Dr. Reisa Sperling at Brigham and Women{\textquoteright}s Hospital, Harvard Medical School, and Dr. Paul Aisen at the Alzheimer{\textquoteright}s Therapeutic Research Institute (ATRI), University of Southern California. The A4 and LEARN studies are coordinated by ATRI at the University of Southern California, and the data are made available through the Laboratory for Neuro Imaging at the University of Southern California. The participants screening for the A4 Study provided permission to share their de-identified data in order to advance the quest to find a successful treatment for Alzheimer{\textquoteright}s disease. Funding Information: Disclosures: RY, KCH and JRS are full-time employees and minor shareholders of Eli Lilly and Company. RY has received funds from Eli Lilly and Company for attending meetings and or/travel. JC has received research funding from NIH and Janssen. MCD has received research funding from NIH and Janssen; consulting fees from Roche; has participated on a Data Safety Monitoring Board or Advisory Board for the University of California, San Diego and has a spouse who is a full-time employee of Janssen. KK has received research funding from NIH and ADDF; consulting fees from Biogen; support for attending meetings and/or travel from Alzheimer{\textquoteright}s Association; has participated on a Data Safety Monitoring Board or Advisory Board for Takeda; has a leadership or fiduciary role in other board, society, committee or advocacy group for Alzheimer{\textquoteright}s Association (unpaid) and NIH and has received research materials from Avid Radiopharmaceuticals. CRJ Jr. has received research funding from NIH, the GHR Foundation, and the Alexander Family Alzheimer{\textquoteright}s Disease Research Professorship of the Mayo Clinic; participated on a Data Safety Monitoring Board or Advisory Board for Roche (unpaid); has served as a speaker for Eisai, and consulted for Biogen, but he receives no personal compensation from any commercial entity. SMZ has no conflicts of interest to declare. KAJ has received research funding from NIH; consulting fees from Novartis and has participated on a Data Safety Monitoring Board or Advisory Board for Cerveau (unpaid). PSA has received research funding from NIH, Alzheimer{\textquoteright}s Association and Eli Lilly and Company for the A4 Trial; research agreements with Janssen, Eli Lilly and Company and Eisai; research funding from NIA, the Alzheimer{\textquoteright}s Association and FNIH and consulting fees from Biogen, Roche, Merck, Abbvie, Immunobrain Checkpoint, Rainbow Medical and Shionogi. RAS has received research funding from NIH, Alzheimer{\textquoteright}s Association and Eli Lilly and Company for the current study; research funding from Eli Lilly and Company, Janssen, NIA, Alzheimer{\textquoteright}s Association; consulting fees from AC Immune, Acumen, Alnylam, Cytox, Janssen, JOMDD, Nervgen, Neuraly, Neurocentria, Oligomerix, Prothema, Renew, Shionogi, Vigil Neuroscience, Ionis, Biogen, Eisai and Roche; honoraria for Harvard HUBWeek Panel (2018), Japan JSNM (2018), Marc Diamond UT Southwestern Symposium (2019), University of Chicago DOM Weekly Grand Rounds Seminar Series (2020), Virtual Rhode Island IDeA Symposium (2020) and Virtual IMPACT-AD Course (2020) and support for attending meetings and/or travel from Duke Lectureship (2018), Alzheimer Research Roundtable (2018), ADPD Symposium (2019), University of Tokyo Roundtable (2019), Biogen: ARIA State of the Art meeting (2019), University of Pittsburgh Distinguished Scientist Lecture (2019), University of Cincinnati Lurie Lecture (2019), UC Irvine Distinguished Lecture on the Brain (2020), Virtual Rhode Island IDeA Symposium (2020), Adler Foundation Symposium San Diego (2020), UC Irvine Lecture (2020) Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = oct,
doi = "10.14283/jpad.2022.56",
language = "English (US)",
volume = "9",
pages = "617--624",
journal = "The journal of prevention of Alzheimer's disease",
issn = "2426-0266",
publisher = "Springer International Publishing AG",
number = "4",
}