Inferior temporal tau is associated with accelerated prospective cortical thinning in clinically normal older adults
Matthew R. Scott,
Olivia L. Hampton,
Rachel F. Buckley,
Jasmeer P. Chhatwal,
Bernard J. Hanseeuw,
Heidi IL. Jacobs,
Michael J. Properzi,
Justin S. Sanchez,
Keith A. Johnson,
Reisa A. Sperling,
Aaron P. Schultz
Affiliations
Matthew R. Scott
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Olivia L. Hampton
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Rachel F. Buckley
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Melbourne School of Psychological Science, University of Melbourne, Victoria, Australia
Jasmeer P. Chhatwal
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Bernard J. Hanseeuw
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Cliniques Universitaires Saint-Luc, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium
Heidi IL. Jacobs
Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, the Netherlands; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Michael J. Properzi
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Justin S. Sanchez
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Keith A. Johnson
Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Reisa A. Sperling
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Aaron P. Schultz
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Corresponding author. Massachusetts General Hospital/Harvard Medical School, 149 13th Street, Suite 10.036, Charlestown, MA, 02129, United States.
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 (Aβ). 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 [18F]-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 at 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.
