A study of the clinical features of PIB-negative dementia patients in amyloid PET

• Project/Area Number: 21613007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Non-invasive neuroimaging
• Research Institution: Osaka City University
• Principal Investigator: SHIMADA Hiroyuki 大阪市立大学, 大学院・医学研究科, 准教授 (90254391)
• Co-Investigator(Kenkyū-buntansha): ATAKA Suzuka 大阪市立大学, 大学院・医学研究科, 研究医 (40549755) ; MIKI Takami 大阪市立大学, 大学院・医学研究科, 教授 (90174002) ; WATANABE Yasuyoshi 大阪市立大学, 大学院・医学研究科, 特任教授 (40144399)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: アミロイドPET / アルツハイマー病 / バイオマーカー / アミロイド陰性認知症 / アミロイドペット / アルツハイマー型認知症 / 高齢者タウオパチー

Research Abstract

Background/Aims : We previously found that some cases of clinically diagnosed Alzheimer's disease(AD) were rated as Pittsburgh compound-B(PiB)-negative by amyloid imaging(ie, cases of PiB-negative dementia). These may involve diseases that do not have pathological amyloid accumulation in the brain, such as dementia with Lewy bodies(DLB), frontotemporal lobar degeneration(FTLD), argyrophilic grain disease(AGD), and neurofibrillary tangle-predominant dementia(NFTD), as well as AD itself. The present study was designed to analyze the clinical features of PiB-negative dementia patients in detail with cerebrospinal fluid(CSF) analysis and neuroradiological tests. Methods : Of the 64 cases of clinically diagnosed AD, 14 were rated PiB-negative with PiB-positron emission tomography(PET). Eleven of these were further analyzed using CSF biomarker levels and findings from magnetic resonance imaging(MRI), fluorodeoxyglucose(FDG)-PET,<123>^I-metaiodobenzylguanidine(MIBG) myocardial scintigraphy, and voxel-based morphometry(VBM). Results : When examined by<123>^I-MIBG myocardial scintigraphy, the PiB-negative dementia group differed slightly from the healthy control group in both the early and delayed phases, and the H/M ratio was significantly higher in the PiB-negative dementia group than in the DLB group. Analyses of CSF biomarkers and MRI and FDG-PET findings among the 11 cases of PiB-negative dementia suggested AGD in 3 cases, FTLD in 3 cases, NFTD in 1 case, and AD in 2 cases. Conclusion : PiB-negative dementia is unlikely to include DLB, while it most likely includes diseases of tauopathy, such as FTLD, AGD, and NFTD. A better understanding of PiB-negative dementia is expected to further improve the accuracy of clinical diagnosis of AD.

Research Products

• [Journal Article] Genetic polymorphysms involved in dopaminergic neurotrasmission and risk for Parkinson's disease in a Japanease population (2011)
  • Author(s): Kiyohara, Y. Miyake, M. Koyanagi, T. Fujimoto, S. Shirasawa, K. Tanaka, W Fukushima, S. Sasaki, Y. Tsuboi, T. Yamada, T. Oeda, H. Shimada, et al.
  • Journal Title: BMC Neurology C Volume: 11 Pages: 89-97
  • Peer Reviewed
• [Journal Article] Two cases of dementias with motor neuron disease evaluated by Pittsburgh compound B-positron emission tomography (2011)
  • Author(s): Y. Yamakawa, H. Shimada, S. Ataka, A. Tamura, H. Masaki, H. Naka, T. Tsutada, A. Nakanishi, . Shiomi, Y. Watanabe, T. Miki
  • Journal Title: Neurological scien Volume: 33 Pages: 87-92
  • Peer Reviewed
• [Journal Article] PiB-negative dementia-a possibility of misdiagnosis of patients with non-Alzheimer's disease(AD) type dementia as having AD. (2011)
  • Author(s): H. Shimada, S. Ataka, J. Takeuchi, H. Mori, S. Wada, Y. Watanabe, T. Miki
  • Journal Title: J Geriatric Psy Nerulogy Volume: 24 Pages: 123-126
  • Peer Reviewed
• [Journal Article] Clinical Course of Patients with Familial Early-Onset Alzheimer's Disease Potentially Lacking Senile Plaques Bearing the E693Delta Mutation in Amyloid Precursor Protein (2011)
  • Author(s): H. Shimada, S. Ataka, T. Tomiyama, H. Takechi, H. Mori, T. Miki.
  • Journal Title: Dement Geriatr Cogn Disord Volume: 32 Pages: 45-54
  • Peer Reviewed
• [Journal Article] Dietary patterns and risk of Parkinson's disease : a case-control study in Japan (2011)
  • Author(s): Hitomi Okuboa, Yoshihiro Miyake, Satoshi Sasakia, Kentaro Murakami, Keiko Tanaka, Wakaba Fukushima, Chikako Kiyoharaf Yoshio Tsuboi, Tatsuo Yamada, Tomoko Oedah, Hiroyuki Shimadai, et al.
  • Journal Title: European J Neurol Volume: 11 Pages: 89-97
  • Peer Reviewed
• [Journal Article] Pittsburgh Compound B-Negative Dementia-A Possibility of Misdiagnosis of Patients With Non-AlzheimerDisease-Type Dementia as Having AD (2011)
  • Author(s): Shimada H, Ataka S, Takeuchi J, Mori H, Wada Y, Watanabe Y, Miki T
  • Journal Title: Journal of Geriatric Psychiatry and Neurology Volume: 24 Issue: 3 Pages: 123-126
  • DOI: 10.1177/0891988711409410
  • Peer Reviewed
• [Journal Article] Genetic polymorphysms involved in dopaminergic neurotrasmission and risk for Parkinson's disease in a Japanease population (2011)
  • Author(s): O.Kiyouaia, T.Miyake, M.Koyanagi, T.Fujimoto, S.Shirasawa, K.Tanaka, W.Fukushima, S.Sasaki, Y.Tsuboi, T.Yamada, T.Oeda, H.Shimada, et al
  • Journal Title: BMC Neurology Volume: 11 Issue: 1 Pages: 89-97
  • DOI: 10.1186/1471-2377-11-89
  • Peer Reviewed
• [Journal Article] Two cases of dementias with motor neuron disease evaluated by Pittsburgh compound B-positron emission tomography (2011)
  • Author(s): Yamakawa Y, Shimada H, Ataka S, Tamura A, Masaki H, Naka H, Tsutada T, Nakanishi A, Shiomi S, Watanabe Y, Miki T.
  • Journal Title: Neurol Sci Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] PiB -negative dementia -a possibility of misdiagnosis of patients with non-Alzheimer's disease (AD) type dementia as having AD (2011)
  • Author(s): H.Shimada, S.Ataka, J.Takeuchi, H.Mori, S.Wada, Y.Watanabe, T.Miki
  • Journal Title: J Geriatric Psy Nerulogy Volume: (In press)
  • Peer Reviewed
• [Journal Article] A mouse model of amiloidβoligomers : their contribution to synaptic alteration, abnoraml tau phosphorylation, glial activation (2010)
  • Author(s): Takami Tomiyama, Shogo Matsuyama, Hiroyuki Iso, Tomohiro Umeda, Hiroshi Takuma, Kiyouhisa Ohnishi, Kenichi Ishibashi, Rie Teraoka, Naomi Sakama, Takenari Yamashita, Kazuchika Nishitsuji, Kazuhiro Ito, Hiroyuki Shimada, et al.
  • Journal Title: J Neuroscience Volume: 30(14) Pages: 4845-4856
  • Peer Reviewed
• [Journal Article] アミロイドイメージングをめぐる問題点-アルツハイマー病以外のデータ- (2010)
  • Author(s): 嶋田裕之、安宅鈴香、三木隆己
  • Journal Title: Cognition and Dementia Volume: 9 Pages: 33-37
• [Journal Article] Neuropsychological Status of Elderly Patients with Diabetes Mellitus. (2010)
  • Author(s): Hiroyuki Shimada
  • Journal Title: Diabetes Research and Clinical Practice 87 Pages: 224-227
  • Peer Reviewed
• [Journal Article] Neuropsychological Status of Elderly Patients with Diabetes Mellitus (2009)
  • Author(s): Hiroyuki Shimada, Takami Miki, Akiko Tamura, Suzuka Ataka, Masanori Emoto, Yoshiki Nishizawa
  • Journal Title: Diabetes Research and Clinical Practice Pages: 224-227
  • Peer Reviewed
• [Journal Article] High strial amyloidβ-peptide deposition across differential Alzheimer disease mutation types (2009)
  • Author(s): Victor L. Villemagne, Suzuka Ataka, Toshiki Mizuno, William S. Brooks, Yasuhiro Wada, Masaki Kondo, Gareth Jones, ; Yasuyoshi Watanabe, ; Rachel Mulligan, Masanori Nakagawa, Takami Miki, Hiroyuki Shimada, et al.
  • Journal Title: Arch Neurol Volume: 66 Pages: 1537-1544
  • Peer Reviewed
• [Journal Article] High strial amyloid β-peptide deposition across differential Alzheimer disease mutation types (2009)
  • Author(s): Victor L.Villemagne, et al
  • Journal Title: Archives of Neurology 66 Pages: 1537-1544
  • Peer Reviewed
• [Presentation] Intravenous immunoglobulin improved cognitive functions in patients with Alzheimer's disease without any changes in PIB retention in the brain (2011)
  • Author(s): Takahiko Tokuda, Masaki Kondo, Takashi Kasai, Yoko Oishi, Suzuka Ataka, Hiroyuki Shimada, Takami Miki, Hiroshi Mori, and Masanori Nakagawa
  • Place of Presentation: フランス、パリ
  • Year and Date: 2011-07-18
• [Presentation] Follow-up study of PiB negative dementia International Conference on Alzheimer's Disease (2011)
  • Author(s): Suzuka Ataka, Hiroyuki Shimada, Jun Takeuchi, Akitoshi Takeda, Akiko Tamura, Motokatsu Kanemoto, Kazuhiro Ito, Jyoji Kawabe, Kazuhiro Takahashi, Yasuhiro Wada, Aki Nakanishi, Tsuyoshi Tsutada, Susumu Shiomi, Hiroshi Mori, Yasuyoshi Watanabe, Takami Miki
  • Place of Presentation: フランス、パリ
  • Year and Date: 2011-07-17
• [Presentation] Intravenous immunoglobulin improved cognitive functions in patients with Alzheimer's disease without any changes in PIB retention in the brain (2011)
  • Author(s): Takaiko Tokoua, Masaki Konuo, Takashi Kasai, Yoko Oishi, Suzuka Ataka, Hiroyuki Shimada, et al
  • Organizer: International Conference on Alzheimer's Disease
  • Place of Presentation: Paris, France
  • Year and Date: 2011-07-17
• [Presentation] Follow-up study of PiB negative dementia (2011)
  • Author(s): Suzuka Ataka, Hiroyuki Shimada, Jun Takeuchi, Akitoshi Takeda, Akiko Tamura, et al
  • Organizer: International Conference on Alzheimer's Disease
  • Place of Presentation: Paris, France
  • Year and Date: 2011-07-16
• [Presentation] 1231-MIBG心筋シンチグラフィーによるPiB陰性認知症の鑑別診断の検討 (2010)
  • Author(s): 竹内潤, 安宅鈴香, 嶋田裕之, 河連譲治勢, 和国康弘, 蔦田強司, 塩見進, 中西亜紀, 三木隆己, 森啓, 渡遵恭良
  • Organizer: 第29回日本認知症学会学術集会
  • Place of Presentation: 名古屋(ウィンク愛知)
  • Year and Date: 2010-11-06
• [Presentation] Both PiB positive and negative MCIs have similar risk of conversion to dementia (2010)
  • Author(s): S.Ataka, H.Shimada, J.Takeuchi, J.Kawabe, K.Takahashi, Y Wada, A.Nakanish, T.Tsutada, S.Shiomi, H.Mori, Y.Watanabe, T.Miki
  • Organizer: International Conference of Arzheimer's disease2011
  • Place of Presentation: 米国 ホノルル
  • Year and Date: 2010-07-12
• [Presentation] Characteristics of Neuropsychological Findings of Clinically Diagnosed Alzheimer's Disease and Mild Cognitive Impairment Patients Who Show Negative Results in Amyloid Imaging (2010)
  • Author(s): H.Takechi, S.Ataka, M.Nishida., T.Miki, H.Shimada
  • Organizer: ICAD 2010 (International Conference of Arzheimer's disease)
  • Place of Presentation: 米国 ホノルル
  • Year and Date: 2010-07-12
• [Presentation] Characteristics of Neuropsychological Findings of Clinically Diagnosed Alzheimer's Disease and Mild Cognitive Impairment Patients Who Show Negative Results in Amyloid Imaging (2010)
  • Author(s): H. Takeuchi, S. Ataka, M. Nishida, T. Miki, H. Shimada
  • Organizer: Alzheimer's Association International Conference on Alzheimer's Disease
  • Place of Presentation: ホノルル、ハワイ
  • Year and Date: 2010-07-11
• [Presentation] Both PiB positive and negative MCIs have similar risk of conversion to dementia (2010)
  • Author(s): Suzuka Ataka, Hiroyuki Shimada, Jun Takeuchi, Jyoji Kawabe, Kazuhiro Takahashi, Yasuhiro Wada, Aki Nakanishi, Tsuyoshi Tsutada, Susumu Shiomi, Hiroshi Mori, Yasuyoshi Watanabe, Takami Miki
  • Organizer: Alzheimer's Association International Conference on Alzheimer's Disease
  • Place of Presentation: ホノルル、ハワイ
  • Year and Date: 2010-07-11
• [Presentation] 医療機関を受診する軽度認知障害(MCI)はPiB-PETでのアミロイド集積の有無にかかわらず認知症へ移行するリスクが高い (2010)
  • Author(s): 安宅鈴香、嶋田裕之、竹内潤, 他
  • Organizer: 第52回日本老年病学会
  • Place of Presentation: 神戸(神戸国際会議場・神戸商工会議所・神戸ポートピアホテル)
  • Year and Date: 2010-06-25
• [Presentation] Biochemical analysis of intracellular oligomers (2009)
  • Author(s): Yamamoto K. Shimada H. Mori H.
  • Organizer: Neuroscience
  • Place of Presentation: 米国、シカゴ
  • Year and Date: 2009-11-13
• [Presentation] ^<11>C-PIB-PET imaging and cognitive statement in Alzheimer disease, mild cognitive impairment, and healthy aging : 1-1.5 Year follow-up study. (2009)
  • Author(s): Suzuka Ataka
  • Organizer: 12th International conference of Alzheimer's disease
  • Place of Presentation: オーストリア、ウィーン
  • Year and Date: 2009-07-14
• [Presentation] ^<11> C-PIB-PET imaging and cognitive statement in Alzheimer disease, mild cognitive impairment, and healthy aging : 1-1.5 Year follow-up study (2009)
  • Author(s): Suzuka Ataka, Hiroyuki Shimada, Jun Takeuchi, Jyoji Kawabe, Makoto Shigematsu, Yasuhiro Wada, Aki Nakanishi, Tsuyoshi Tsutada, Susumu Shiomi, Hiroshi Mori, Yasuyoshi Watanabe, Takami Miki
  • Organizer: 12th International conference of Alzheimer's disease
  • Place of Presentation: オーストリア、ウィーン
  • Year and Date: 2009-07-13
• [Presentation] PiB negative Dementia.-Pitfall of clinical diagnosis of Alzheimer's disease (2009)
  • Author(s): H. SHIMADA, S. ATAKA, J. TAKEUCHI, A. NAKANISHI, J. KAWABE, S. SHIOMI, H. MORI, T. MIKI, M. SHIGEMATSU, Y. WADA, Y. WATANABE
  • Organizer: 12th International conference of Alzheimer's disease
  • Place of Presentation: オーストリア、ウィーン
  • Year and Date: 2009-07-12
• [Presentation] PiB negative Dementia -Pitfall of clinical diagnosis of Alzheimer's disease (2009)
  • Author(s): H.SHIMADA
  • Organizer: 12th International conference of Alzheimer's disease
  • Place of Presentation: オーストリア、ウィーン
  • Year and Date: 2009-07-12