Clinical outcomes of increased focal amyloid uptake in individuals with subthreshold global amyloid levels

BACKGROUND: Although the standardized uptake value ratio (SUVR) method is objective and simple, cut-off optimization using global SUVR values may not reflect focal increased uptake in the cerebrum. The present study investigated clinical and neuroimaging characteristics according to focally increased β-amyloid (Aβ) uptake and global Aβ status. METHODS: We recruited 968 participants with cognitive continuum. All participants underwent neuropsychological tests and 498 (18)F-florbetaben (FBB) amyloid positron emission tomography (PET) and 470 (18)F-flutemetamol (FMM) PET. Each PET scan was assessed in 10 regions (left and right frontal, lateral temporal, parietal, cingulate, and striatum) with focal-quantitative SUVR-based cutoff values for each region by using an iterative outlier approach. RESULTS: A total of 62 (6.4%) subjects showed increased focal Aβ uptake with subthreshold global Aβ status [global (−) and focal (+) Aβ group, G(−)F(+) group]. The G(−)F(+) group showed worse performance in memory impairment (p < 0.001), global cognition (p = 0.009), greater hippocampal atrophy (p = 0.045), compared to those in the G(−)F(−). Participants with widespread Aβ involvement in the whole region [G(+)] showed worse neuropsychological (p < 0.001) and neuroimaging features (p < 0.001) than those with focal Aβ involvement G(−)F(+). CONCLUSION: Our findings suggest that individuals show distinctive clinical outcomes according to focally increased Aβ uptake and global Aβ status. Thus, researchers and clinicians should pay more attention to focal increased Aβ uptake in addition to global Aβ status.