Abstract
A true understanding of the distribution and functional correlates of Alzheimer’s disease pathology in dementia-free older adults requires a population-based perspective. Here we report initial findings from a sample of 102 cognitively unimpaired participants (average age 77.2 years, 54.9% women, 13.7% APOE*4 carriers) recruited for neuroimaging from a larger representative population-based cohort participating in an ongoing longitudinal study of aging, the Monongahela-Youghiogheny Healthy Aging Team (MYHAT). All participants scored < 1.0 on the Clinical Dementia Rating (CDR) Scale, with 8 participants (7.8%) scoring CDR = 0.5. Participants completed a positron emission tomography scan using the tracers [C-11]Pittsburgh Compound-B (PiB) and [F-18]AV-1451 to estimate amyloid and tau deposition. PiB positivity was defined on a regional basis using established standardized uptake value ratio cutoffs (SUVR; cerebellar gray matter reference), with 39 participants (38.2%) determined to be PiB(+). Health history, lifestyle, and cognitive abilities were assessed cross-sectionally at the nearest annual parent MYHAT study visit. A series of adjusted regression analyses modeled cognitive performance as a function of global PiB SUVR and [F-18]AV-1451 SUVR in Braak associated regions 1, 3/4, and 5/6. In comparison to PiB(-) participants (n = 63), PiB(+) participants were older, less educated, and were more likely to be APOE*4 carriers. Global PiB SUVR was significantly correlated with [F-18]AV-1451 SUVR in all Braak-associated regions (r = .38–0.53, p < .05). In independent models, higher Global PiB SUVR and Braak 1 [F-18]AV-1451 SUVR were associated with worse performance on a semantic interference verbal memory test. Our findings suggest that brain amyloid is common in a community-based setting, and is associated with tau deposition, but both pathologies show few associations with concurrent cognitive performance in a dementia-free sample.
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Acknowledgements
The authors thank Erin Jacobsen, Amy Carper, and Keith Van Horn for administrative, data management, and study recruitment support for MYHAT-NI. We are grateful to all of the staff of the Pittsburgh PET Research Center, and the participants and staff of the MYHAT and MYHAT-NI studies.
Funding
This work was supported by the National Institute on Aging at the National Institute of Health (R01 AG052521, R01 AG023651, RF1 AG025516, R01 AG030650, R01 AG064877, and T32 AG000181).
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GE Healthcare holds a license agreement with the University of Pittsburgh based on the PiB PET technology used in this manuscript. Dr. Klunk is a co-inventor of PiB and, as such, has a financial interest in this license agreement. GE Healthcare provided no grant support for this study and had no role in the design or interpretation of results or preparation of this manuscript. All other authors have no conflicts of interest with this work, had full access to all of the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis.
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Sullivan, K.J., Liu, A., Chang, CC.H. et al. Alzheimer’s disease pathology in a community-based sample of older adults without dementia: The MYHAT neuroimaging study. Brain Imaging and Behavior 15, 1355–1363 (2021). https://doi.org/10.1007/s11682-020-00334-2
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DOI: https://doi.org/10.1007/s11682-020-00334-2