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Abstract
Background and purpose: Alzheimer's disease (AD) does not always mean amyloid positivity. [18F]THK-5351 has been shown to be able to detect reactive astrogliosis as well as tau accompanied by neurodegenerative changes. We evaluated the [18F]THK-5351 retention patterns in positron-emission tomography (PET) and the clinical characteristics of patients clinically diagnosed with AD dementia who had negative amyloid PET findings.

Methods: We performed 3.0-T magnetic resonance imaging, [18F]THK-5351 PET, and amyloid PET in 164 patients with AD dementia. Amyloid PET was visually scored as positive or negative. [18F]THK-5351 PET were visually classified as having an intratemporal or extratemporal spread pattern.

Results: The 164 patients included 23 (14.0%) who were amyloid-negative (age 74.9±8.3 years, mean±standard deviation; 9 males, 14 females). Amyloid-negative patients were older, had a higher prevalence of diabetes mellitus, and had better visuospatial and memory functions. The frequency of the apolipoprotein E ε4 allele was higher and the hippocampal volume was smaller in amyloid-positive patients. [18F]THK-5351 uptake patterns of the amyloid-negative patients were classified into intratemporal spread (n=10) and extratemporal spread (n=13). Neuropsychological test results did not differ significantly between these two groups. The standardized uptake value ratio of [18F]THK-5351 was higher in the extratemporal spread group (2.01±0.26 vs. 1.61±0.15, p=0.001). After 1 year, Mini Mental State Examination (MMSE) scores decreased significantly in the extratemporal spread group (-3.5±3.2, p=0.006) but not in the intratemporal spread group (-0.5±2.8, p=0.916). The diagnosis remained as AD (n=5, 50%) or changed to other diagnoses (n=5, 50%) in the intratemporal group, whereas it remained as AD (n=8, 61.5%) or changed to frontotemporal dementia (n=4, 30.8%) and other diagnoses (n=1, 7.7%) in the extratemporal spread group.

Conclusions: Approximately 70% of the patients with amyloid-negative AD showed abnormal [18F]THK-5351 retention. MMSE scores deteriorated rapidly in the patients with an extratemporal spread pattern.

Affiliations

Minyoung Oh  1 , Jungsu S Oh  1 , Seung Jun Oh  1 , Sang Ju Lee  1 , Jee Hoon Roh  2 , Woo Ram Kim  3 , Ha-Eun Seo  3 , Jae Myeong Kang  4 , Sang Won Seo  5 , Jae-Hong Lee  2 , Duk L Na  5 , Young Noh  3   6 , Jae Seung Kim  7
1 Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
2 Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
3 Neuroscience Research Institute, Gachon University, Incheon, Korea.
4 Department of Psychiatry, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea.
5 Department of Neurology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Korea.
6 Department of Neurology, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea. ynoh@gilhospital.com.
7 Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. jaeskim@amc.seoul.kr.