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Abstract
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 18F-florbetaben (FBB) amyloid positron emission tomography (PET) and 470 18F-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.

Affiliations

Jaeho Kim 1 2 3 4, Yeong Sim Choe 1 5, Yuhyun Park 1 5, Yeshin Kim 6, Jun Pyo Kim 1 2 3 7, Hyemin Jang 1 2 3, Hee Jin Kim 1 2 3, Duk L Na 1 2 3 5 8, Soo-Jin Cho 4, Seung Hwan Moon 9, Sang Won Seo 1 2 3 5 10
1Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
2Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea.
3Samsung Alzheimer Research Center, Samsung Medical Center, Seoul, Republic of Korea.
4Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong-si, Gyeonggi-do, Republic of Korea.
5Department of Health Sciences and Technology, SAIHST, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea.
6Department of Neurology, Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do, Republic of Korea.
7Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States.
8Samsung Medical Center, Stem Cell and Regenerative Medicine Institute, Seoul, Republic of Korea.
9Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
10Department of Clinical Research Design and Evaluation, SAIHST, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea.