TY - JOUR
T1 - Inferring changepoint times of medial temporal lobe morphometric change in preclinical Alzheimer's disease
AU - Younes, Laurent
AU - Albert, Marilyn
AU - Miller, Michael I.
N1 - Funding Information:
This study is supported in part by grants from the National Institutes of Health : U01-AG03365 , P50- AG005146 , P41-EB015909 and R01-EB000975 . The BIOCARD Study consists of 7 Cores with the following members: (1) the Administrative Core (Marilyn Albert and Barbara Rodzon), (2) the Clinical Core (Ola Selnes, Marilyn Albert, Rebecca Gottesman, Ned Sacktor, Guy McKhann, Scott Turner, Leonie Farrington, Maura Grega, Daniel D'Agostino, Sydney Feagen, David Dolan, Hillary Dolan), (3) the Imaging Core (Michael Miller, Susumu Mori, Tilak Ratnanather, Timothy Brown, Anthony Kolasny, Kenichi Oishi, William Schneider, Laurent Younes), (4) the Biospecimen Core (Richard O'Brien, Abhay Moghekar, Richard Meehan), (5) the Informatics Core (Roberta Scherer, Curt Meinert, David Shade, Ann Ervin, Jennifer Jones, Matt Toepfner, Lauren Parlett, April Patterson, Lisa Lassiter), the (6) Biostatistics Core (Mei-Cheng Wang, Yi Lu, Qing Cai), and (7) the Neuropathology Core (Juan Troncoso, Barbara Crain, Olga Pletnikova, Gay Rudow, Karen Fisher).We are grateful to the members of the BIOCARD Scientific Advisory Board who provide continued oversight and guidance regarding the conduct of the study including: Drs. John Csernansky, David Holtzman, David Knopman, Walter Kukull and John McArdle, as well as Drs. Neil Buckholtz, John Hsiao, Laurie Ryan and Jovier Evans, who provide oversight on behalf of the NIA and the NIMH, respectively. We would also like to thank 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 the study (PI: Dr. Trey Sunderland). We are particularly indebted to Dr. Karen Putnam, who has provided ongoing documentation of the GPB study procedures and the data files received from NIMH.
PY - 2014
Y1 - 2014
N2 - This paper uses diffeomorphometry methods to quantify the order in which statistically significant morphometric change occurs in three medial temporal lobe regions, the amygdala, entorhinal cortex (ERC), and hippocampus among subjects with symptomatic and preclinical Alzheimer's disease (AD). Magnetic resonance imaging scans were examined in subjects who were cognitively normal at baseline, some of whom subsequently developed clinical symptoms of AD. The images were mapped to a common template, using shape-based diffeomorphometry. The multidimensional shape markers indexed through the temporal lobe structures were modeled using a changepoint model with explicit parameters, specifying the number of years preceding clinical symptom onset. Our model assumes that the atrophy rate of a considered brain structure increases years before detectable symptoms. The results demonstrate that the atrophy changepoint in the ERC occurs first, indicating significant change 8-10 years prior to onset, followed by the hippocampus, 2-4 years prior to onset, followed by the amygdala, 3 years prior to onset. The ERC is significant bilaterally, in both our local and global measures, with estimates of ERC surface area loss of 2.4% (left side) and 1.6% (right side) annually. The same changepoint model for ERC volume gives 3.0% and 2.7% on the left and right sides, respectively. Understanding the order in which changes in the brain occur during preclinical AD may assist in the design of intervention trials aimed at slowing the evolution of the disease.
AB - This paper uses diffeomorphometry methods to quantify the order in which statistically significant morphometric change occurs in three medial temporal lobe regions, the amygdala, entorhinal cortex (ERC), and hippocampus among subjects with symptomatic and preclinical Alzheimer's disease (AD). Magnetic resonance imaging scans were examined in subjects who were cognitively normal at baseline, some of whom subsequently developed clinical symptoms of AD. The images were mapped to a common template, using shape-based diffeomorphometry. The multidimensional shape markers indexed through the temporal lobe structures were modeled using a changepoint model with explicit parameters, specifying the number of years preceding clinical symptom onset. Our model assumes that the atrophy rate of a considered brain structure increases years before detectable symptoms. The results demonstrate that the atrophy changepoint in the ERC occurs first, indicating significant change 8-10 years prior to onset, followed by the hippocampus, 2-4 years prior to onset, followed by the amygdala, 3 years prior to onset. The ERC is significant bilaterally, in both our local and global measures, with estimates of ERC surface area loss of 2.4% (left side) and 1.6% (right side) annually. The same changepoint model for ERC volume gives 3.0% and 2.7% on the left and right sides, respectively. Understanding the order in which changes in the brain occur during preclinical AD may assist in the design of intervention trials aimed at slowing the evolution of the disease.
KW - AD
KW - Abbreviations
KW - Alzheimer's disease
KW - CDR
KW - Clinical Center of the National Institutes of Health
KW - ERC
KW - FWER
KW - GPB
KW - Geriatric Psychiatry Branch
KW - MCI
KW - MMSE
KW - NIA
KW - NIH
KW - NIMH
KW - National Institute for Mental Health
KW - National Institute on Aging
KW - ROI-LDDMM
KW - RSS
KW - SPGR
KW - clinical dementia rating
KW - diffeomorphometry
KW - entorhinal cortex
KW - family-wise error rate
KW - mild cognitive impairment
KW - mini-mental state exam
KW - region-of-interest large deformation diffeomorphic metric mapping
KW - residual sum of squares
KW - spoiled gradient echo
KW - study of shape using a metric on the diffeomorphic connections between structures
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U2 - 10.1016/j.nicl.2014.04.009
DO - 10.1016/j.nicl.2014.04.009
M3 - Article
C2 - 25101236
AN - SCOPUS:84904874330
SN - 2213-1582
VL - 5
SP - 178
EP - 187
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
ER -