@article{fe3f3c5f0ed440a8ab0e17792523652e,
title = "Inferior temporal tau is associated with accelerated prospective cortical thinning in clinically normal older adults",
abstract = "Neurofibrillary tau tangles are a hallmark pathology of Alzheimer's disease (AD) and are more closely associated with AD-related cortical atrophy and symptom severity than amyloid-beta (A beta). However, studies regarding the effect of tau on longitudinal cortical thinning, particularly in healthy aging and preclinical AD, have been limited in number due to the relatively recent introduction of in vivo PET tracers for imaging tau pathology. Here, we investigate [18H-flortaucipir (FTP, a marker of paired helical filament tau) PET as a predictor of atrophy in healthy aging and preclinical AD. We examine longitudinal structural MRI brain imaging data, retrospectively and prospectively relative to FTP imaging, using piecewise linear mixed-effect models with time centered a each participant's FTP-PET session. Participants include 111 individuals from the Harvard Aging Brain Study who underwent at least three MRI sessions over an average of 4.46 years and one FTP-PET at the approximate midpoint of the observation period. Our primary analyses focus on inferior temporal (IT) FTP standardized uptake value ratios and longitudinal FreeSurfer defined cortical regions of interest. Relationships were also explored using other regional FTP measures (entorhinal, composite, and local), within high and low Pittsburgh compound-B (PiB) PET groups, and with longitudinal subcortical volume. Strong associations between IT FTP and cortical thinning were found, most notably in temporal, midline, and prefrontal regions, with stronger effects generally observed in the prospective as compared to retrospective time frame. Significant differences between prospective and retrospective rates of thinning were found in the inferior and middle temporal gyri, cingulate areas, as well as pars orbitalis such that higher IT FTP was associated with greater prospective rates of thinning. Within the high PiB group, significant differences between prospective and retrospective rates of thinning were similarly observed. However, no consistent pattern of tau-related change in cortical thickness within the low PiB group was discerned. These results provide support for the hypothesis that tau pathology is a driver of future atrophy as well as provide additional evidence for tau-PET as an effective AD biomarker for interventional clinical trials.",
keywords = "Cortical thinning, Tau, Longitudinal modeling, Flortaucipir, PET, MRI, Alzheimer's disease, Imaging, ALZHEIMERS-DISEASE, COGNITIVE DECLINE, IN-VIVO, ATROPHY, NEURODEGENERATION, DEMENTIA, MILD, METABOLISM, PATHOLOGY",
author = "Scott, {Matthew R.} and Hampton, {Olivia L.} and Buckley, {Rachel F.} and Chhatwal, {Jasmeer P.} and Hanseeuw, {Bernard J.} and Jacobs, {Heidi I. L.} and Properzi, {Michael J.} and Sanchez, {Justin S.} and Johnson, {Keith A.} and Sperling, {Reisa A.} and Schultz, {Aaron P.}",
note = "Funding Information: Dr. Schultz has received grants from the National Institute on Aging and served on paid advisory boards for Janssen Pharmaceuticals (2013) and Biogen (2016). Dr. Hanseeuw is funded by the Belgian National Fund for Scientific Research (FNRS) #SPD28094292. Dr. Jacobs reported funding from the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant agreement (IF-2015-GF, 706714). Dr. Johnson has served as a paid consultant for Bayer, GE Healthcare, Janssen, Siemens Medical Solutions, Genzyme, Novartis, Biogen, Roche, AZTherapy, GEHC, Lundbeck, Genentech, Lilly/Avid, AC Immune, and Abbvie. Dr. Sperling has received grants from National Institute on Aging, Alzheimer's Association, Eli Lilly and Co., and Janssen Pharmaceuticals. She has consulted for AC Immune, Eisai, Janssen, Roche, and Takeda. There are no other conflicts of interest to be reported.We would like to acknowledge the participants of the Harvard Aging Brain Study for their dedication. This work was supported with funding from National Institutes of Health grants via R01AG027435 and for the Harvard Aging Brain Study (P01AG036694) and R01AG046396 (Dr. Johnson). This research was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies (P41EB015896), a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, S10RR021110, S10RR023401, S10RR019307, S10RR019254, and S10RR023043. Funding Information: We would like to acknowledge the participants of the Harvard Aging Brain Study for their dedication. This work was supported with funding from National Institutes of Health grants via R01AG027435 and for the Harvard Aging Brain Study ( P01AG036694 ) and R01AG046396 (Dr. Johnson). This research was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies ( P41EB015896 ), a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health . This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, S10RR021110 , S10RR023401 , S10RR019307 , S10RR019254 , and S10RR023043 . Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = oct,
day = "15",
doi = "10.1016/j.neuroimage.2020.116991",
language = "English",
volume = "220",
journal = "Neuroimage",
issn = "1053-8119",
publisher = "Elsevier Science",
}