Abstract
Alzheimer's disease is a neurodegenerative disease in which the degree of cortical atrophy in specific structures of the brain serves as a useful imaging biomarker. Recent approaches using linear mixed effects (LME) models in longitudinal neuroimaging have been powerful and flexible in investigating the temporal trajectories of cortical thickness. However, massive-univariate analysis, a simplified approach that obtains a summary statistic (e.g., a p-value) for every vertex along the cortex, is insufficient to model cortical atrophy because it does not account for spatial similarities of the signals in neighboring locations. In this article, we develop a permutation-based inference procedure to detect spatial clusters of vertices showing statistically significant differences in the rates of cortical atrophy. The proposed method, called SpLoc, uses spatial information to combine the signals adaptively across neighboring vertices, yielding high statistical power while controlling family-wise error rate (FWER) accurately. When we reject the global null hypothesis, we use a cluster selection algorithm to detect the spatial clusters of significant vertices. We validate our method using simulation studies and apply it to the Alzheimer's Disease Neuroimaging Initiative (ADNI) data to show its superior performance over existing methods. An R package for implementing SpLoc is publicly available.
Original language | English (US) |
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Article number | 118312 |
Journal | NeuroImage |
Volume | 239 |
DOIs | |
State | Published - Oct 1 2021 |
Bibliographical note
Funding Information:Data collection and sharing for this project was 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. The authors appreciate the editor and anonymous reviewers for their helpful and constructive comments. Also, the authors would like to thank Ning Dai (Ph.D. Statistics, University of Minnesota) and Jin Jin (Ph.D. Biostatistics, University of Minnesota) for their helpful comments on data preprocessing. The computing resources were supported by the Minnesota Supercomputing Institute (MSI). Jun Young Park was supported by the MnDRIVE Informatics PhD Graduate Assistantship Program at the University of Minnesota.
Funding Information:
The authors appreciate the editor and anonymous reviewers for their helpful and constructive comments. Also, the authors would like to thank Ning Dai (Ph.D. Statistics, University of Minnesota) and Jin Jin (Ph.D. Biostatistics, University of Minnesota) for their helpful comments on data preprocessing. The computing resources were supported by the Minnesota Supercomputing Institute (MSI). Jun Young Park was supported by the MnDRIVE Informatics PhD Graduate Assistantship Program at the University of Minnesota.
Funding Information:
Data collection and sharing for this project was 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:
© 2021 The Author(s)
Keywords
- Alzheimer's disease
- Cortical atrophy
- Linear mixed effects
- Permutation
- Spatially localized signals
- Statistical analysis