@article{e774ba3bb9ca468f807dbfec00ccd2c6,
title = "A flexible modeling approach for biomarker-based computation of absolute risk of Alzheimer's disease dementia",
abstract = "Introduction: As Alzheimer's disease (AD) biomarkers rapidly develop, tools are needed that accurately and effectively communicate risk of AD dementia. Methods: We analyzed longitudinal data from >10,000 cognitively unimpaired older adults. Five-year risk of AD dementia was modeled using survival analysis. Results: A demographic model was developed and validated on independent data with area under the receiver operating characteristic curve (AUC) for 5-year prediction of AD dementia of 0.79. Clinical and cognitive variables (AUC = 0.79), and apolipoprotein E genotype (AUC = 0.76) were added to the demographic model. We then incorporated the risk computed from the demographic model with hazard ratios computed from independent data for amyloid positron emission tomography status and magnetic resonance imaging hippocampal volume (AUC = 0.84), and for plasma amyloid beta (Aβ)42/Aβ40 (AUC = 0.82). Discussion: An adaptive tool was developed and validated to compute absolute risks of AD dementia. This approach allows for improved accuracy and communication of AD risk among cognitively unimpaired older adults.",
keywords = "return of research results, risk estimation, survival analysis",
author = "Hartz, {Sarah M.} and Jessica Mozersky and Suzanne Schindler and Erin Linnenbringer and Junwei Wang and Brian Gordon and Raji, {Cyrus A.} and Moulder, {Krista L.} and Tim West and Benzinger, {Tammie L.S.} and Carlos Cruchaga and Hassenstab, {Jason J.} and Bierut, {Laura J.} and Chengjie Xiong and John Morris",
note = "Funding Information: The authors acknowledge the expert assistance of NACC in compiling and providing the database. The NACC database is funded by NIA/NIH Grant U01 AG016976. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG062428-01 (PI James Leverenz, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P30 AG062421-01 (PI Bradley Hyman, MD, PhD), P30 AG062422-01 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P30 AG062429-01(PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P30 AG062715-01 (PI Sanjay Asthana, MD, FRCP), P30 AG066444 (PI John C. Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD). This study was funded by NIH grants R01 AG065234 (SMH, JM, EL, JW), P01 AG026276 (SMH, JM, JW, TAB, KLM, CX, JCM), 5 P01 AG003991 (TAB, KLM, CX, JCM), P30 AG066444 (KLM, CX, JCM), 1 UL1 TR002345 (SMH, LJB), NIH R44 AG059489 (TW), and R01AG07094 (SES). Other funding was from BrightFocus CA2016636 (TW), The Gerald and Henrietta Rauenhorst (GHR) Foundation, and the Alzheimer's Drug Discovery Foundation (ADDF# GC-201711- 2013978, TW). The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Sarah M. Hartz had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Publisher Copyright: {\textcopyright} 2022 the Alzheimer's Association.",
year = "2023",
month = apr,
doi = "10.1002/alz.12781",
language = "English",
volume = "19",
pages = "1452--1465",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
number = "4",
}