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

BackgroundAlthough 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 beta-amyloid (A beta) uptake and global A beta status. MethodsWe recruited 968 participants with cognitive continuum. All participants underwent neuropsychological tests and 498 F-18-florbetaben (FBB) amyloid positron emission tomography (PET) and 470 F-18-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. ResultsA total of 62 (6.4%) subjects showed increased focal A beta uptake with subthreshold global A beta status [global (-) and focal (+) A beta 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 A beta involvement in the whole region [G(+)] showed worse neuropsychological (p < 0.001) and neuroimaging features (p < 0.001) than those with focal A beta involvement G(-)F(+). ConclusionOur findings suggest that individuals show distinctive clinical outcomes according to focally increased A beta uptake and global A beta status. Thus, researchers and clinicians should pay more attention to focal increased A beta uptake in addition to global A beta status.