@article{08a996043f28481d90ed3f4b0ab34fd7,
title = "Disentangling tau and brain atrophy cluster heterogeneity across the Alzheimer's disease continuum",
abstract = "INTRODUCTION: Neuroimaging heterogeneity in dementia has been examined using single modalities. We evaluated the associations of magnetic resonance imaging (MRI) atrophy and flortaucipir positron emission tomography (PET) clusters across the Alzheimer's disease (AD) spectrum.METHODS: We included 496 Alzheimer's Disease Neuroimaging Initiative participants with brain MRI, flortaucipir PET scan, and amyloid beta biomarker measures obtained. We applied a novel robust collaborative clustering (RCC) approach on the MRI and flortaucipir PET scans. We derived indices for AD-like (SPARE-AD index) and brain age (SPARE-BA) atrophy.RESULTS: We identified four tau (I-IV) and three atrophy clusters. Tau clusters were associated with the apolipoprotein E genotype. Atrophy clusters were associated with white matter hyperintensity volumes. Only the hippocampal sparing atrophy cluster showed a specific association with brain aging imaging index. Tau clusters presented stronger clinical associations than atrophy clusters. Tau and atrophy clusters were partially associated.CONCLUSIONS: Each neuroimaging modality captured different aspects of brain aging, genetics, vascular changes, and neurodegeneration leading to individual multimodal phenotyping.",
keywords = "Alzheimer's disease, amyloid beta, heterogeneity, mangetic resonance imaging, positron emission tomography, prognosis, tau",
author = "{for the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative} and Toledo, {Jon B.} and Hangfan Liu and Grothe, {Michel J.} and Tanweer Rashid and Lenore Launer and Shaw, {Leslie M.} and Haykel Snoussi and Susan Heckbert and Michael Weiner and Trojanwoski, {John Q.} and Sudha Seshadri and Mohamad Habes",
note = "Funding Information: Jon B. Toledo is supported by the Edmond J. Safra Fellowship in Movement Disorders. Michel J. Grothe is supported by the “Miguel Servet” program (CP19/00031) and a research grant (PI20/00613) of the Instituto de Salud Carlos III‐Fondo Europeo de Desarrollo Regional (ISCIII‐FEDER). This study was supported in part by the National Institute of Health (NIH) grant P30AG066546 (South Texas Alzheimer's Disease Research Center) and grant numbers 5R01HL127659, 1U24AG074855 and the San Antonio Medical Foundation grant SAMF–1000003860. Data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI; National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH‐12‐2‐0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol‐Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann‐La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Funding Information: Jon B. Toledo is supported by the Edmond J. Safra Fellowship in Movement Disorders. Michel J. Grothe is supported by the “Miguel Servet” program (CP19/00031) and a research grant (PI20/00613) of the Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (ISCIII-FEDER). This study was supported in part by the National Institute of Health (NIH) grant P30AG066546 (South Texas Alzheimer's Disease Research Center) and grant numbers 5R01HL127659, 1U24AG074855 and the San Antonio Medical Foundation grant SAMF–1000003860. Data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI; National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Publisher Copyright: {\textcopyright} 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.",
year = "2022",
doi = "10.1002/trc2.12305",
language = "English (US)",
volume = "8",
pages = "e12305",
journal = "Alzheimer's and Dementia: Translational Research and Clinical Interventions",
issn = "2352-8737",
publisher = "Elsevier",
number = "1",
}