HAI Book 2025 - Flipbook - Page 82
Mormino, Elizabeth
Pathological and clinical trajectories of preclinical Alzheimer9s disease
patients with divergent cortical tau patterns
Christina Young1, Mackenzie Carlson1, Karly Cody1, Joseph Winer1, Aaron Schultz2, Elizabeth
Mormino1
1
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, US
Department of Neurology, Massachusetts General Hospital, Boston, MA, US
2
Background: We previously demonstrated that approximately 9% of cognitively unimpaired (CU) older adults with
elevated ยด-amyloid (A+) exhibit more than expected cortical than medial temporal lobe (MTL) tau and/or having
high cortical tau asymmetry (A+TCortical+).
Objective: To characterize longitudinal tau patterns and clinical trajectories of A+TCortical+ and determine whether
trajectories differ from those with elevated medial temporal lobe tau (A+TMTL+).
Methods: 18F-flortaucipir tau PET and clinical data spanning up to 8 years [mean (SD) = 4.68 (1.59) years] were
examined in 393 CU participants enrolled in A4/LEARN (Table 1). Participants were determined to be in A-TMTL(n=47), A-TMTL+ (n=1), A+TMTL- (n=211), A+TMTL+ (n=100), and A+TCortical+ (n=34) groups based on baseline amyloid and
tau PET scans. We examined change in tau PET SUVR and asymmetry, as well as clinical trajectories were
compared across groups using linear mixed effects models.
Results: A+TCortical+ participants accumulated tau in cortical regions that already showed relatively high SUVRs at
baseline. Participants with asymmetrical tau at baseline accumulated tau in the corresponding region in the
opposite hemisphere in addition to new regions in the original hemisphere (Figure 1, 2A). MTL SUVRs increased at
comparable rates for the A+TCortical+ group compared to other A+ groups, but SUVRs in all cortical regions
increased significantly faster in the A+TCortical+ group (Figure 2B, 2C). The A+TCortical+ group showed faster cognitive
and functional decline (Figure 2D, 2E). Results were consistent when further accounting for baseline global tau
and baseline amyloid, further indicating that findings were not driven by overall high levels of baseline pathology.
Conclusion: A+ CU with divergent cortical tau patterns are an especially high-risk subgroup. These participants
continue to accumulate cortical tau at a faster rate than other preclinical AD subgroups and are at increased risk
for faster cognitive and functional decline.
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