Using the Alzheimer's Disease Neuroimaging Initiative to improve early detection, diagnosis, and treatment of Alzheimer's disease

Dallas P Veitch; Michael W Weiner; Paul S Aisen; Laurel A Beckett; Charles DeCarli; Robert C Green; Danielle Harvey; Clifford R Jack Jr; William Jagust; Susan M Landau; John C Morris; Ozioma Okonkwo; Richard J Perrin; Ronald C Petersen; Monica Rivera-Mindt; Andrew J Saykin; Leslie M Shaw; Arthur W Toga; Duygu Tosun; John Q Trojanowski; Alzheimer's Disease Neuroimaging Initiative

doi:10.1002/alz.12422

Using the Alzheimer's Disease Neuroimaging Initiative to improve early detection, diagnosis, and treatment of Alzheimer's disease

Alzheimers Dement. 2022 Apr;18(4):824-857. doi: 10.1002/alz.12422. Epub 2021 Sep 28.

Authors

Dallas P Veitch^{1

2}, Michael W Weiner^{1

3

4

5

6}, Paul S Aisen⁷, Laurel A Beckett⁸, Charles DeCarli⁹, Robert C Green¹⁰, Danielle Harvey⁸, Clifford R Jack Jr¹¹, William Jagust¹², Susan M Landau¹², John C Morris¹³, Ozioma Okonkwo¹⁴, Richard J Perrin^{13

15

16}, Ronald C Petersen¹⁷, Monica Rivera-Mindt¹⁸, Andrew J Saykin^{19

20}, Leslie M Shaw²¹, Arthur W Toga²², Duygu Tosun³, John Q Trojanowski²¹; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, California, USA.
² Department of Veterans Affairs Medical Center, Northern California Institute for Research and Education (NCIRE), San Francisco, California, USA.
³ Department of Radiology, University of California, San Francisco, San Francisco, California, USA.
⁴ Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
⁵ Department of Psychiatry, University of California, San Francisco, San Francisco, California, USA.
⁶ Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
⁷ Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, California, USA.
⁸ Division of Biostatistics, Department of Public Health Sciences, University of California Davis, Davis, California, USA.
⁹ Department of Neurology and Center for Neuroscience, University of California Davis, Davis, California, USA.
¹⁰ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Broad Institute, Ariadne Labs, and Harvard Medical School, Boston, Massachusetts, USA.
¹¹ Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
¹² Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, USA.
¹³ Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, Missouri, USA.
¹⁴ Wisconsin Alzheimer's Disease Research Center and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
¹⁵ Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA.
¹⁶ Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
¹⁷ Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
¹⁸ Department of Psychology, Fordham University, New York, New York, USA.
¹⁹ Department of Radiology and Imaging Sciences and Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
²⁰ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
²¹ Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Research, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²² Laboratory of Neuroimaging, USC Stevens Institute of Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Abstract

Introduction: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has accumulated 15 years of clinical, neuroimaging, cognitive, biofluid biomarker and genetic data, and biofluid samples available to researchers, resulting in more than 3500 publications. This review covers studies from 2018 to 2020.

Methods: We identified 1442 publications using ADNI data by conventional search methods and selected impactful studies for inclusion.

Results: Disease progression studies supported pivotal roles for regional amyloid beta (Aβ) and tau deposition, and identified underlying genetic contributions to Alzheimer's disease (AD). Vascular disease, immune response, inflammation, resilience, and sex modulated disease course. Biologically coherent subgroups were identified at all clinical stages. Practical algorithms and methodological changes improved determination of Aβ status. Plasma Aβ, phosphorylated tau181, and neurofilament light were promising noninvasive biomarkers. Prognostic and diagnostic models were externally validated in ADNI but studies are limited by lack of ethnocultural cohort diversity.

Discussion: ADNI has had a profound impact in improving clinical trials for AD.

Keywords: AV1541 tau positron emission tomography; Alzheimer's disease; amyloid; disease progression; mild cognitive impairment; plasma biomarker; tau.

Publication types

Review

MeSH terms

Alzheimer Disease* / diagnostic imaging
Alzheimer Disease* / genetics
Amyloid beta-Peptides
Biomarkers
Cognitive Dysfunction*
Disease Progression
Humans
Neuroimaging / methods
tau Proteins

Substances

Amyloid beta-Peptides
Biomarkers
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding