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Longitudinal inferior temporal FTP‐PET signal increase is associated with contemporaneous longitudinal temporal lobe cortical thinning in preclinical Alzheimer’s disease
Author(s) -
Hampton Olivia L.,
Buckley Rachel F.,
Properzi Michael J.,
Chhatwal Jasmeer P.,
Johnson Keith A.,
Sperling Reisa A.,
Schultz Aaron P.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.043419
Subject(s) - temporal lobe , nuclear medicine , pittsburgh compound b , psychology , alzheimer's disease , medicine , neuroscience , pathology , disease , epilepsy
Background Flortaucipir (FTP)‐PET enables visualization of in vivo paired helical filament tangles, a hallmark of Alzheimer’s disease (AD) pathological progression. Due to its recent implementation, most studies have only analyzed its cross‐sectional associations. This work leverages longitudinal measurements of inferior temporal (IT)‐FTP to better understand the temporal relationship of tau accumulation and neurodegeneration through analyzing the change in IT‐FTP signal on change in contemporaneous cortical thickness across the brain in clinically‐normal (CN) older adults. Method T1‐weighted MRI scans were processed using Freesurfer (FS) v6 longitudinal pipeline (Reuter et al., 2012) and we computed bi‐hemispheric thickness values in all 34 ROIs. 18 F FTP‐PET images in 124 participants (2‐3 timepoints, range 1.21‐5.19 years; Table 1) were aligned within subject before being co‐registered to FS longitudinal base images. SUVR measures were calculated using cerebellar gray as the reference region, with IT signal used as a tau proxy for all analyses. Participants also underwent 11 C Pittsburgh Compound‐B (PiB) imaging at baseline. We calculated slopes with respect to time for IT tau signal and cortical thickness in each ROI using linear regressions for each participant. For all analyses, we used IT‐FTP slope to predict thickness slope in each ROI using a linear regression covarying for sex and baseline age. We also divided our sample into PiB+ (N=41) and PiB‐ (N=83) groups based on a global 1.186 PiB DVR threshold to understand the impact of IT tau change on cortical thinning in a preclinical AD (PiB+) sample. Result Greater IT tau slopes were associated with accelerated contemporaneous cortical thinning in temporal regions (Fig. 1A). PiB+ individuals were found to drive the IT‐FTP slope effect on temporal atrophy ( p s < 0.001, Fig. 1B, 2). Particularly, the entorhinal cortex showed the strongest effect ( t (37); p <0.00005; Fig. 2). No ROI in the PiB‐ group yielded a significant IT tau slope‐associated rate of atrophy (Fig. 1C). Conclusion We found that in CNs with increasing IT‐FTP signal, temporal regions are susceptible to neurodegeneration. However, high PiB individuals drive this relationship. Our longitudinal results confirm previous research with cross‐sectional IT tau and provide evidence for contemporaneous cortical thinning in temporal regions in preclinical late onset AD.

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