TY - JOUR
T1 - A Japanese Multicenter Study on PET and Other Biomarkers for Subjects with Potential Preclinical and Prodromal Alzheimer’s Disease
AU - Senda, Michio
AU - Ishii, K.
AU - Ito, K.
AU - Ikeuchi, T.
AU - Matsuda, H.
AU - Iwatsubo, T.
AU - Iwata, A.
AU - Ihara, R.
AU - Suzuki, K.
AU - Kasuga, K.
AU - Ikari, Y.
AU - Niimi, Y.
AU - Arai, H.
AU - Tamaoka, A.
AU - Arahata, Y.
AU - Itoh, Y.
AU - Tachibana, H.
AU - Ichimiya, Y.
AU - Washizuka, S.
AU - Odawara, T.
AU - Ishii, K.
AU - Ono, K.
AU - Yokota, T.
AU - Nakanishi, A.
AU - Matsubara, E.
AU - Mori, H.
AU - Shimada, H.
N1 - Funding Information:
This study was financially supported by grants from Japan Agency for Medical Research and Development (AMED) 19dk0207020h0005, 20dk0202028h0005 and 20dm0207073h003, as well as by an anonymous Foundation.
Funding Information:
The following conflicts of interest are disclosed by the authors. Senda reports provision of devices, cassettes, and precursors from Avid/ Eli Lilly Japan and GE, funding as PI of clinical trials sponsored by Eli Lilly, Eisai, Biogen, Cerveau and Merck, as well as leadership role in the Japanese Society of Nuclear Medicine as board member, congress chair and committee chair. Ikeuchi reports grants from AMED (JP19dk0207020, JP20dk0202028, JP20dm0207073). Matsuda reports a grant from AMED (19dk0207020h0005), intramural grants from National Center of Neurology and Psychiatry, and an entrusted research fund from Nihon Medi-Physics Co. Ltd. Iwatsubo reports a grant from an anonymous Foundation. Iwata reports grants from AMED (19dk0207020h0005, 16dk0207028h0001). Ikari is a full time employee of CMIC Inc. as well as graduate student of Osaka University. Washizuka reports research funding from AMED and pharmaceutical companies including Otsuka, Eisai, Pfizer, Daiichi-Sankyo, Tsumura, Mochida, Astellas, Shionogi, Takeda, Sumitomo-Dainippon, as well as honoraria from such pharmaceutical companies. Kazunari Ishii reports honoraria from Nihon Medi-Physics. Yokota reports licensing and collaboration research with Takeda Pharmaceutical Company. Nakanishi reports research funding from Eisai and Elli Lilly Japan as well as leadership role as a director in the Japan Society for Dementia Research. Shimada reports grants from AMED (19dk0207020h0005, 20dk0207028h0005). The other authors have nothing to disclose.
Funding Information:
We are grateful for the materials and technical supports for the PET imaging by Fujifilm Toyama Chemical, Avid Radiopharmaceuticals/ Eli Lilly Japan, and GE Healthcare. PET centers that imaged the subjects but did not belong to the clinical site that enrolled the subjects are also acknowledged, including Tohoku University Cyclotron and Radioisotope Center (CYRIC), Tsukuba Advanced Imaging Center (AIC), Tokyo Metropolitan Institute of Gerontology (TMIG), Aizawa Hospital, MI Clinic, and Kobe City Medical Center General Hospital (KCGH). We thank all the people who participated in this study in the clinical and imaging sites as well as in the Core sites.
Publisher Copyright:
© 2021, Serdi and Springer Nature Switzerland AG.
PY - 2021/9
Y1 - 2021/9
N2 - Background: PET (positron emission tomography) and CSF (cerebrospinal fluid) provide the “ATN” (Amyloid, Tau, Neurodegeneration) classification and play an essential role in early and differential diagnosis of Alzheimer’s disease (AD). Objective: Biomarkers were evaluated in a Japanese multicenter study on cognitively unimpaired subjects (CU) and early (E) and late (L) mild cognitive impairment (MCI) patients. Measurements: A total of 38 (26 CU, 7 EMCI, 5 LMCI) subjects with the age of 65–84 were enrolled. Amyloid-PET and FDG-PET as well as structural MRI were acquired on all of them, with an additional tau-PET with 18F-flortaucipir on 15 and CSF measurement of Aβ1–42, P-tau, and T-tau on 18 subjects. Positivity of amyloid and tau was determined based on the positive result of either PET or CSF. Results: The amyloid positivity was 13/38, with discordance between PET and CSF in 6/18. Cortical tau deposition quantified with PET was significantly correlated with CSF P-tau, in spite of discordance in the binary positivity between visual PET interpretation and CSF P-tau in 5/8 (PET−/CSF+). Tau was positive in 7/9 amyloid positive and 8/16 amyloid negative subjects who underwent tau measurement, respectively. Overall, a large number of subjects presented quantitative measures and/or visual read that are close to the borderline of binary positivity, which caused, at least partly, the discordance between PET and CSF in amyloid and/or tau. Nine subjects presented either tau or FDG-PET positive while amyloid was negative, suggesting the possibility of non-AD disorders. Conclusion: Positivity rate of amyloid and tau, together with their relationship, was consistent with previous reports. Multicenter study on subjects with very mild or no cognitive impairment may need refining the positivity criteria and cutoff level as well as strict quality control of the measurements.
AB - Background: PET (positron emission tomography) and CSF (cerebrospinal fluid) provide the “ATN” (Amyloid, Tau, Neurodegeneration) classification and play an essential role in early and differential diagnosis of Alzheimer’s disease (AD). Objective: Biomarkers were evaluated in a Japanese multicenter study on cognitively unimpaired subjects (CU) and early (E) and late (L) mild cognitive impairment (MCI) patients. Measurements: A total of 38 (26 CU, 7 EMCI, 5 LMCI) subjects with the age of 65–84 were enrolled. Amyloid-PET and FDG-PET as well as structural MRI were acquired on all of them, with an additional tau-PET with 18F-flortaucipir on 15 and CSF measurement of Aβ1–42, P-tau, and T-tau on 18 subjects. Positivity of amyloid and tau was determined based on the positive result of either PET or CSF. Results: The amyloid positivity was 13/38, with discordance between PET and CSF in 6/18. Cortical tau deposition quantified with PET was significantly correlated with CSF P-tau, in spite of discordance in the binary positivity between visual PET interpretation and CSF P-tau in 5/8 (PET−/CSF+). Tau was positive in 7/9 amyloid positive and 8/16 amyloid negative subjects who underwent tau measurement, respectively. Overall, a large number of subjects presented quantitative measures and/or visual read that are close to the borderline of binary positivity, which caused, at least partly, the discordance between PET and CSF in amyloid and/or tau. Nine subjects presented either tau or FDG-PET positive while amyloid was negative, suggesting the possibility of non-AD disorders. Conclusion: Positivity rate of amyloid and tau, together with their relationship, was consistent with previous reports. Multicenter study on subjects with very mild or no cognitive impairment may need refining the positivity criteria and cutoff level as well as strict quality control of the measurements.
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U2 - 10.14283/jpad.2021.37
DO - 10.14283/jpad.2021.37
M3 - Article
C2 - 34585225
AN - SCOPUS:85108907532
VL - 8
SP - 495
EP - 502
JO - The journal of prevention of Alzheimer's disease
JF - The journal of prevention of Alzheimer's disease
SN - 2426-0266
IS - 4
ER -