@article{ff506def32594b3f9c27eb4b8e681b8a,
title = "Entorhinal and Transentorhinal Atrophy in Preclinical Alzheimer's Disease",
abstract = "This study examines the atrophy patterns in the entorhinal and transentorhinal cortices of subjects that converted from normal cognition to mild cognitive impairment. The regions were manually segmented from 3T MRI, then corrected for variability in boundary definition over time using an automated approach called longitudinal diffeomorphometry. Cortical thickness was calculated by deforming the gray matter-white matter boundary surface to the pial surface using an approach called normal geodesic flow. The surface was parcellated based on four atlases using large deformation diffeomorphic metric mapping. Average cortical thickness was calculated for (1) manually-defined entorhinal cortex, and (2) manually-defined transentorhinal cortex. Group-wise difference analysis was applied to determine where atrophy occurred, and change point analysis was applied to determine when atrophy started to occur. The results showed that by the time a diagnosis of mild cognitive impairment is made, the transentorhinal cortex and entorhinal cortex was up to 0.6 mm thinner than a control with normal cognition. A change point in atrophy rate was detected in the transentorhinal cortex 9–14 years prior to a diagnosis of mild cognitive impairment, and in the entorhinal cortex 8–11 years prior. The findings are consistent with autopsy findings that demonstrate neuronal changes in the transentorhinal cortex before the entorhinal cortex.",
keywords = "change point, cortical thickness, diffeomorphometry, entorhinal, preclinical, transentorhinal",
author = "{Alzheimer's Disease Neuroimaging Initiative} and Sue Kulason and Eileen Xu and Tward, {Daniel J.} and Arnold Bakker and Marilyn Albert and Laurent Younes and Miller, {Michael I.}",
note = "Funding Information: A special thank you to Kanami Mori for her work on manually segmenting the 11T ex vivo MRI atlas and to Anthony Kolasny for maintaining the Center for Imaging Science server on which much of this analysis was run. Data used in the preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. 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 DODADNI (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 Neuroimaging at the University of Southern California. Data from the BIOCARD study are supported by grant U19 AG033655 from the National Institute on Aging. The BIOCARD Study consists of 7 Cores with the following members: (1) The Administrative Core (MA, Barbara Rodzon), (2) the Clinical Core (MA, Anja Soldan, Rebecca Gottesman, Ned Sacktor, Corinne Pettigrew, Scott Turner, Leonie Farrington, Maura Grega, Jules, Gilles, Gay Rudow, Rostislav Brichko, Scott Rudow), (3) the Imaging Core (MM, Susumu Mori, Tilak Ratnanather, Anthony Kolasny, Hanzhang Lu, Kenichi Oishi, LY), (4) the Biospecimen Core (Abhay Moghekar, Jacqueline Darrow, Richard O'Brien), (5) the Informatics Core (Roberta Scherer, David Shade, Ann Ervin, Jennifer Jones, Hamadou Coulibaly, Kathy Moser), the (6) Biostatistics Core (Mei-Cheng Wang, Yuxin Zhu, Jiangxia Wang), and (7) the Neuropathology Core (Juan Troncoso, Olga Pletnikova, Karen Fisher). We would also like to acknowledge the members of the BIOCARD Scientific Advisory Board who provide oversight an guidance regarding the conduct of the study including: Drs. John Csernansky, David Holtzman, David Knopman, Walter Kukull and Kevin Duff, as well as Drs. Laurie Ryan and John Hsiao, who provide oversight on behalf of the NIA. Additionally, we recognize the members of the BIOCARD Resource Allocation Committee who provide ongoing guidance regarding the use of the biospecimens collected as part of the study, including: Drs. Constantine Lyketsos, Carlos Pardo, Gerard Schellenberg, Leslie Shaw, Madhav Thambisetty, and John Trojanowski. We would like to acknowledge the contributions of the Geriatric Psychiatry Branch (GPB) of the intramural program of the NIMH who initiated this study (PI: Dr. Trey Sunderland). Dr. Karen Putnam provided documentation of the GPB study procedures and the datafiles received from NIMH. We acknowledge the altruism of the participants and their families and contributions of the BIOCARD research and support staff for their contributions to this study. Funding. This work was supported by the National Institutes of Health (P41-EB015909 and R01-EB020062); and the Kavli Neuroscience Discovery Institute. MM reports personal fees from AnatomyWorks, LLC, outside the submitted work, and jointly owns AnatomyWorks. Dr. Miller's relationship with AnatomyWorks is being handled under full disclosure by the Johns Hopkins University. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Kulason, Xu, Tward, Bakker, Albert, Younes, and Miller.",
year = "2020",
month = aug,
day = "21",
doi = "10.3389/fnins.2020.00804",
language = "English (US)",
volume = "14",
journal = "Frontiers in Neuroscience",
issn = "1662-4548",
publisher = "Frontiers Research Foundation",
}