The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022

Dallas P Veitch; Michael W Weiner; Melanie Miller; Paul S Aisen; Miriam A Ashford; Laurel A Beckett; Robert C Green; Danielle Harvey; Clifford R Jack Jr; William Jagust; Susan M Landau; John C Morris; Kwangsik T Nho; Rachel Nosheny; Ozioma Okonkwo; Richard J Perrin; Ronald C Petersen; Monica Rivera Mindt; Andrew Saykin; Leslie M Shaw; Arthur W Toga; Duygu Tosun; Alzheimer's Disease Neuroimaging Initiative

doi:10.1002/alz.13449

The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022

Alzheimers Dement. 2024 Jan;20(1):652-694. doi: 10.1002/alz.13449. Epub 2023 Sep 12.

Authors

Dallas P Veitch^{1

2}, Michael W Weiner^{2

3

4

5

6}, Melanie Miller^{1

2}, Paul S Aisen⁷, Miriam A Ashford¹, Laurel A Beckett⁸, Robert C Green⁹, Danielle Harvey⁸, Clifford R Jack Jr¹⁰, William Jagust¹¹, Susan M Landau¹¹, John C Morris^{12

13

14}, Kwangsik T Nho^{15

16}, Rachel Nosheny^{2

5}, Ozioma Okonkwo¹⁷, Richard J Perrin^{12

13

14}, Ronald C Petersen¹⁸, Monica Rivera Mindt^{19

20}, Andrew Saykin^{15

21}, Leslie M Shaw²², Arthur W Toga²³, Duygu Tosun^{2

3}; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Department of Veterans Affairs Medical Center, Northern California Institute for Research and Education (NCIRE), San Francisco, California, USA.
² Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, California, USA.
³ Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
⁴ Department of Medicine, University of California, San Francisco, California, USA.
⁵ Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, California, USA.
⁶ Department of Neurology, University of California, 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, California, USA.
⁹ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Broad Institute Ariadne Labs and Harvard Medical School, Boston, Massachusetts, USA.
¹⁰ Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
¹¹ Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, USA.
¹² Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, Missouri, USA.
¹³ Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA.
¹⁴ Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
¹⁵ Department of Radiology and Imaging Sciences and the Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁶ Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁷ Wisconsin Alzheimer's Disease Research Center and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
¹⁸ Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
¹⁹ Department of Psychology, Latin American and Latino Studies Institute, African and African American Studies, Fordham University, New York, New York, USA.
²⁰ Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
²¹ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
²² Department of Pathology and Laboratory Medicine and the PENN Alzheimer's Disease Research Center, Center for Neurodegenerative Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²³ Laboratory of Neuro Imaging, Institute of Neuroimaging and Informatics, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

Abstract

The Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to improve Alzheimer's disease (AD) clinical trials. Since 2006, ADNI has shared clinical, neuroimaging, and cognitive data, and biofluid samples. We used conventional search methods to identify 1459 publications from 2021 to 2022 using ADNI data/samples and reviewed 291 impactful studies. This review details how ADNI studies improved disease progression understanding and clinical trial efficiency. Advances in subject selection, detection of treatment effects, harmonization, and modeling improved clinical trials and plasma biomarkers like phosphorylated tau showed promise for clinical use. Biomarkers of amyloid beta, tau, neurodegeneration, inflammation, and others were prognostic with individualized prediction algorithms available online. Studies supported the amyloid cascade, emphasized the importance of neuroinflammation, and detailed widespread heterogeneity in disease, linked to genetic and vascular risk, co-pathologies, sex, and resilience. Biological subtypes were consistently observed. Generalizability of ADNI results is limited by lack of cohort diversity, an issue ADNI-4 aims to address by enrolling a diverse cohort.

Keywords: Alzheimer's Disease Neuroimaging Initiative; Alzheimer's disease clinical trials; Alzheimer's disease subtypes; amyloid; cerebrovascular disease; co-pathologies; diagnosis; disease progression; generalizability; neurodegeneration; neuroinflammation; plasma biomarkers; prediction; resilience; tau.

Publication types

Review
Research Support, N.I.H., Extramural

MeSH terms

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

Substances

Amyloid beta-Peptides
Biomarkers
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding