Optimizing quantification of MK6240 tau PET in unimpaired older adults

Authors

Theresa M. Harrison, University of California Berkeley, USA. Electronic address: tessaharrison@berkeley.edu.
Tyler J. Ward, University of California Berkeley, USA.
Alice Murphy, University of California Berkeley, USA.
Suzanne L. Baker, Lawrence Berkeley National Laboratory, USA.
Pablo A. Dominguez, Lawrence Berkeley National Laboratory, USA.
Robert Koeppe, University of Michigan, USA.
Prashanthi Vemuri, Mayo Clinic, USA.
Samuel N. Lockhart, Wake Forest University School of Medicine, USA.
Youngkyoo Jung, University of California Davis, USA.
Danielle J. Harvey, University of California Davis, USA.
Laura Lovato, Wake Forest University School of Medicine, USA.
Arthur W. Toga, University of Southern California, USA.
Joseph Masdeu, Houston Methodist, USA.
Hwamee Oh, Brown University, USA.
Darren R. Gitelman, Advocate Health - MidwestFollow
Neelum Aggarwal, Rush University Medical Center, USA.
Heather M. Snyder, Alzheimer's Association, USA.
Laura D. Baker, Wake Forest University School of Medicine, USA.
Charles DeCarli, University of California Davis, USA.
William J. Jagust, University of California Berkeley, USA; Lawrence Berkeley National Laboratory, USA.
Susan M. Landau, University of California Berkeley, USA.

Recommended Citation

Harrison TM, Ward TJ, Murphy A, et al. Optimizing quantification of MK6240 tau PET in unimpaired older adults. Neuroimage. 2023;265:119761. doi:10.1016/j.neuroimage.2022.119761

Abstract

Accurate measurement of Alzheimer's disease (AD) pathology in older adults without significant clinical impairment is critical to assessing intervention strategies aimed at slowing AD-related cognitive decline. The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (POINTER) is a 2-year randomized controlled trial to evaluate the effect of multicomponent risk reduction strategies in older adults (60-79 years) who are cognitively unimpaired but at increased risk for cognitive decline/dementia due to factors such as cardiovascular disease and family history. The POINTER Imaging ancillary study is collecting tau-PET ([18F]MK6240), beta-amyloid (Aβ)-PET ([18F]florbetaben [FBB]) and MRI data to evaluate neuroimaging biomarkers of AD and cerebrovascular pathophysiology in this at-risk sample. Here 481 participants (70.0±5.0; 66% F) with baseline MK6240, FBB and structural MRI scans were included. PET scans were coregistered to the structural MRI which was used to create FreeSurfer-defined reference regions and target regions of interest (ROIs). We also created off-target signal (OTS) ROIs to examine the magnitude and distribution of MK6240 OTS across the brain as well as relationships between OTS and age, sex, and race. OTS was unimodally distributed, highly correlated across OTS ROIs and related to younger age and sex but not race. Aiming to identify an optimal processing approach for MK6240 that would reduce the influence of OTS, we compared our previously validated MRI-guided standard PET processing and 6 alternative approaches. The alternate approaches included combinations of reference region erosion and meningeal OTS masking before spatial smoothing as well as partial volume correction. To compare processing approaches we examined relationships between target ROIs (entorhinal cortex (ERC), hippocampus or a temporal meta-ROI (MetaROI)) SUVR and age, sex, race, Aβ and a general cognitive status measure, the Modified Telephone Interview for Cognitive Status (TICSm). Overall, the processing approaches performed similarly, and none showed a meaningful improvement over standard processing. Across processing approaches we observed previously reported relationships with MK6240 target ROIs including positive associations with age, an Aβ+> Aβ- effect and negative associations with cognition. In sum, we demonstrated that different methods for minimizing effects of OTS, which is highly correlated across the brain within subject, produced no substantive change in our performance metrics. This is likely because OTS contaminates both reference and target regions and this contamination largely cancels out in SUVR data. Caution should be used when efforts to reduce OTS focus on target or reference regions in isolation as this may exacerbate OTS contamination in SUVR data.

Document Type

Article

PubMed ID

36455762