The Longitudinal Early-onset Alzheimer's Disease Study (LEADS): Framework and methodology

• Type of Material: Article
• Authors: Liana G Apostolova, Indiana University; Paul Aisen, University of Southern California; Ani Eloyan, Brown University; Anne Fagan, Washington University; Keith N Fargo, Charcot Marie Tooth Res Fdn; Tatiana Foroud, Indiana University; Constantine Gatsonis, Brown University; Lea T Grinberg, University of California San Francisco; Clifford R Jack, Mayo Clinic; Joel Kramer, University of California San Francisco; Robert Koeppe, University of Michigan; Walter A Kukull, University of Washington; Melissa E Murray, Mayo Clinic; Kelly Nudelman, Indiana University; Malia Rumbaugh, Indiana University; Arthur Toga, Keck School of Medicine of USC; Prashanthi Vemuri, Mayo Clinic; Amy Trullinger, Indiana University; Leonardo Iaccarino, University of California San Francisco; Gregory S Day, Mayo Clinic; Neil R Graff-Radford, Mayo Clinic; Lawrence S Honig, Columbia University; David T Jones, Mayo Clinic; Joseph Masdeu, Houston Methodist & Weill Cornell Med; Mario Mendez, University of California Los Angeles; Erik Musiek, Washington Univ; Chiadi U Onyike, Johns Hopkins University; Emily Rogalski, Northwestern University; Steve Salloway, Brown University; David A Wolk, University of Pennsylvania; Thomas Wingo, Emory University; Maria C Carrillo, Alzheimers Assoc; Bradford C Dickerson, Massachusetts General Hospital; Gil D Rabinovici, University of California San Francisco
• Language: English
• Date: 2021-05-21
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/alz.12350
• Title of Journal or Parent Work: ALZHEIMERS & DEMENTIA
• Volume: 17
• Issue: 12
• Start Page: 2043
• End Page: 2055
• Grant/Funding Information: This study is generously supported by R56 AG057195, U01AG6057195, U24AG021886, Alzheimer's Association LEADS GENETICS‐19‐639372, U01 AG016976, P30 AG010133, P50 AG008702, P50 AG025688, P50 AG005146, P30 AG062421, P30 AG062422, P50 AG023501, P30 AG010124, P30 AG013854, and P50 AG005681.
• Keywords: ATROPHY; PRESENILE; AGE; EOAD; PATTERNS; GLUCOSE-METABOLISM; DEMENTIA SEVERITY; young onset; Life Sciences & Biomedicine; Neurosciences & Neurology; ASSOCIATION WORKGROUPS; SENILE-DEMENTIA; s disease; Clinical Neurology; YOAD; early‐ Science & Technology; NATIONAL INSTITUTE; DIAGNOSTIC GUIDELINES; Alzheimer' LEADS; onset
• Research Categories: Health Sciences, Epidemiology; Biology, Biostatistics; Health Sciences, Radiology

Abstract

Patients with early-onset Alzheimer's disease (EOAD) are commonly excluded from large-scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals of the Longitudinal EOAD Study (LEADS) are to (1) define the clinical, imaging, and fluid biomarker characteristics of EOAD; (2) develop sensitive cognitive and biomarker measures for future clinical and research use; and (3) establish a trial-ready network. LEADS will follow 400 amyloid beta (Aβ)-positive EOAD, 200 Aβ-negative EOnonAD that meet National Institute on Aging–Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) or AD dementia, and 100 age-matched controls. Participants will undergo clinical and cognitive assessments, magnetic resonance imaging (MRI), [18F]Florbetaben and [18F]Flortaucipir positron emission tomography (PET), lumbar puncture, and blood draw for DNA, RNA, plasma, serum and peripheral blood mononuclear cells, and post-mortem assessment. To develop more effective AD treatments, scientists need to understand the genetic, biological, and clinical processes involved in EOAD. LEADS will develop a public resource that will enable future planning and implementation of EOAD clinical trials.