STOP Dementia Project

• Project/Area Number: 17K19871
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Society medicine, Nursing, and related fields
• Research Institution: Department of Clinical Research, National Hospital Organization Kyoto Medical Center
• Principal Investigator: ryo ohtani 独立行政法人国立病院機構(京都医療センター臨床研究センター), 糖尿病研究部, 研究員 (80574657)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: Alzheimer’s disease / HDL subfraction / high-density lipoprotein / inflammation / cognitive impairment / Dementia / MCI / HDL subclass / apolipoprotein / NLR / 認知症 / 軽度認知障害 / HDL亜分画 / アミロイドβ / HDL-C / アポリポ蛋白A1

Outline of Final Research Achievements

High-density lipoprotein (HDL) containing apolipoprotein A-I is associated with the pathogenesis of Alzheimer's disease (AD).The aim of this study was to investigate the HDL lipoprotein subclasses in mild cognitive impairment (MCI) and AD. This cross-sectional study included 20 AD patients, 17 MCI patients, and 17 age-matched controls without cognitive impairment, selected from the database of the Study of Outcome and aPolipoproteins in Dementia (STOP-Dementia) registry. Small-sized HDL particle levels in the MCI group were significantly higher than in the control group, although there was no difference in serum HDL-cholesterol levels between MCI and control groups. NLR in the MCI group was higher than in the control group, but this difference was non-significant. There was no difference in HDL subclasses or NLR between the AD and control groups. These findings suggest that HDL subclasses might be associated with the development of MCI.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病の早期発見や抗認知症薬に関する研究は進んでいるが、アミロイドβの産生機構に関する基礎的研究も進んでいる。本研究から、軽度認知症の発症にHDLのサブクラスが関与していることが明らかとなった。また、本研究の成果として「ストップ認知症プロジェクト」のデータベースを完成することができた。このデータベースを利用することで、GWASやEWAS、さらにはリピドミクスを駆使することで、アミロイドβの排泄機構の解明されることが期待される。

Research Products

• [Journal Article] Response to Letter to the Editor (2020)
  • Author(s): Ohtani, R. and Sakane, N.
  • Journal Title: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Volume: 29 Pages: 104533-104533
  • Peer Reviewed / Open Access
• [Journal Article] Pretreatment Blood Pressure is a Simple Predictor of Hemorrhagic Infarction after Intravenous Recombinant Tissue Plasminogen Activator (rt-PA) Therapy. (2019)
  • Author(s): Ohtani R, Nakamura M, Nirengi S, Kawakami O, Togawa J, Doi K, Sainouchi M, Kuwata Y, Takata M, Masuda Y, Matsunari R, Takeda K, Tsukahara T, Sakane N.
  • Journal Title: J Stroke Cerebrovasc Dis. Volume: 28 Issue: 7 Pages: 1979-1986
  • DOI: 10.1016/j.jstrokecerebrovasdis.2019.03.035
  • Peer Reviewed / Open Access
• [Journal Article] Bilateral oculomotor nerve palsy in a case of anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (2019)
  • Author(s): Yasuda, K., Maki, T., Takata, M., Kimura, K., Takahashi, T., Kanbayashi, T., Murase, N., Ohtani, R., Takahashi, R. and Nakamura, M.
  • Journal Title: Journal of Clinical Neuroscience Volume: 66 Pages: 271-272
  • Peer Reviewed
• [Journal Article] Effect of Standard vs Intensive Blood Pressure Control on the Risk of Recurrent Stroke A Randomized Clinical Trial and Meta-analysis (2019)
  • Author(s): Kitagawa.K Yamamoto.Y Arima.H Maeda.T Sunami.N Kanzawa.T Eguchi.K Kamiyama.K Minematsu.K Ueda.S Rakugi.H Ohya.Y Kohro.T Yonemoto.K Okada.Y Higaki.J Tanahashi.N Kimura.G Umemura.S Matsumoto.M Shimamoto.K Ito.S Saruta.T Shimada.K Kario.K Saito.Y Terayama.Y Toyoda.K Okura.T Hoshino.H Ohtani.R and 365 others
  • Journal Title: Jama Neurology Volume: 76 Pages: 1309-1318
  • Peer Reviewed / Open Access
• [Journal Article] Two cases of delayed perforating artery infarction adjacent to intracranial hemorrhage (2019)
  • Author(s): Yasuda, K., Maki, T., Kimura, K., Ayaki, T., Sawamoto, N., Murase, N., Ohtani, R., Takahashi, R. and Nakamura, M.
  • Journal Title: eNeurologicalSci Volume: 17 Pages: 100209-100209
  • Peer Reviewed
• [Journal Article] 非細菌性血栓性心内膜炎が原因の脳塞栓症に対し、血栓回収療法を試みた1剖検例 (2019)
  • Author(s): 安田 謙, 綾木 孝, 川端 康弘, 村瀬 永子, 大谷 良, 中村 道三
  • Journal Title: 臨床神経学 Volume: 59 Pages: 195-199
  • NAID: 130007636894
  • Peer Reviewed / Open Access
• [Journal Article] An autopsy case after endovascular thrombectomy for cardioembolic stroke due to nonbacterial thrombotic endocarditis (2019)
  • Author(s): Yasuda K, Ayaki T, Kawabata Y, Murase N, Ohtani R, Nakamura M.
  • Journal Title: Rinsho Shinkeigaku Volume: 59 Issue: 4 Pages: 195-199
  • DOI: 10.5692/clinicalneurol.cn-001252
  • NAID: 130007636894
  • ISSN: 0009-918X, 1882-0654
  • Peer Reviewed
• [Journal Article] Leukoencephalopathy with a case of heterozygous POLG mutation mimicking mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). (2019)
  • Author(s): Yasuda K, Murase N, Yoshinaga K, Ohtani R, Goto YI, Takahashi R, Nakamura M.
  • Journal Title: J Clin Neurosci. Volume: 61 Pages: 302-304
  • DOI: 10.1016/j.jocn.2018.10.054
  • Peer Reviewed / Open Access
• [Journal Article] High-Density Lipoprotein Subclasses and Mild Cognitive Impairment: Study of Outcome and aPolipoproteins in Dementia (STOP-Dementia)1. (2018)
  • Author(s): Ohtani R, Nirengi S, Nakamura M, Murase N, Sainouchi M, Kuwata Y, Takata M, Masuda Y, Kotani K, Sakane N.
  • Journal Title: J Alzheimers Dis. Volume: 66 Issue: 1 Pages: 289-296
  • DOI: 10.3233/jad-180135
  • Peer Reviewed / Open Access
• [Journal Article] Predictors of Cardioembolic Stroke in Japanese Patients with Atrial Fibrillation in the Fushimi AF Registry (2018)
  • Author(s): Yasuda Ken、Fukuda Shunichi、Nakamura Michikazu、Ohtani Ryo、Kuwata Yasuhiro、Takata Masaki、Sainouchi Makoto、Gotou Masahiro、Masuda Yuichi、Kawarazaki Satoru、Kawabata Yasuhiro、Murase Nagako、Aoki Tomokazu、Yonemoto Naohiro、Akao Masaharu、Tsukahara Tetsuya
  • Journal Title: Cerebrovascular Diseases Extra Volume: 8 Issue: 2 Pages: 50-59
  • DOI: 10.1159/000488206
  • Peer Reviewed / Open Access
• [Journal Article] A case of chronic inflammatory demyelinating polyradiculoneuropathy, showing radicular pain due to tuberous hypertrophy of the spinal roots and plexuses after 20 years interval without relapsing sensorimotor symptoms (2018)
  • Author(s): Yasuda K, Murase N, Ohtani R, Oka N, Nakamura M.
  • Journal Title: Rinsho Shinkeigaku Volume: 58 Issue: 1 Pages: 21-24
  • DOI: 10.5692/clinicalneurol.cn-001073
  • NAID: 130006320309
  • ISSN: 0009-918X, 1882-0654
  • Peer Reviewed
• [Journal Article] High-density lipoprotein subclasses and mild cognitive impairment: Study of Outcome and aPolipoproteins in Dementia (STOP-Dementia) (2018)
  • Author(s): Ohtani R, Nirengi S, Nakamura M, Tsuzaki K, Murase N, Sainouchi M, Kuwata Y, Takata M, Masuda Y, Kotani K, Sakane N.
  • Journal Title: Journal of Alzheimer's Disease Volume: -
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 右内頚動脈高度狭窄および右前頭葉小梗塞により 左上下肢の hemichorea-hemiballism を呈した一例 (2019)
  • Author(s): 十川 純平、武田 清明、三村 直哉、松成 亮太、大谷 良
  • Organizer: 第115回日本神経学会近畿地方会（大阪）
• [Presentation] 認知症と共に生きる 講演１：高齢者てんかんと認知症 (2019)
  • Author(s): 大谷 良
  • Organizer: 伏見医師会 市民公開講座（京都）
• [Presentation] Association of serum apolipoprotein A1 levels with atherothrombotic infarction and plaque properties of carotid artery. (2019)
  • Author(s): Ryo Ohtani, Shinsuke Nirengi, Jumpei Togawa, Masato Kinboshi, Kiyoaki Takeda, Naoya Mimura, Ryota Matsunari, Kazuhiko Kotani, Tetsuya Tsukahara, Michikazu Nakamura, Naoki Sakane
  • Organizer: World Congress of Neurology (WCN) 2019 Dubai, UAE
• [Presentation] rt-PA療法後の出血性脳梗塞の予測因子：治療前の血圧管理の重要性 (2018)
  • Author(s): 大谷 良、中村道三、二連木晋輔、川上理、村瀬永子、斎ノ内信、桑田康弘、高田真基、増田裕一、土井健人、塚原徹也、坂根直樹
  • Organizer: 第43回 日本脳卒中学会学術集会
• [Presentation] 脳卒中既往のある心房細動患者における予後と脳卒中/全身塞栓症の発症危険因子：伏見AFレジストリ (2018)
  • Author(s): 増田 裕一,大谷 良,福田 俊一,桒田 康弘,高田 真基,斉ノ内 信,土井 健人 ,河原崎 知,川上 理,村瀬 永子,塚原 徹也 ,赤尾 昌治,中村 道三
  • Organizer: 第43回 日本脳卒中学会学術集会
• [Presentation] 大動脈粥状硬化病変からの塞栓症 認知症の謎を探る (2018)
  • Author(s): 大谷 良
  • Organizer: 12th Trans Catheter Imaging Forum
• [Presentation] Comparison of apolipoprotein A1 and carotid artery ultrasonography findings among stroke subtypes and controls (2018)
  • Author(s): Ryo Ohtani, Shinsuke Nirengi, Michikazu Nakamura , Jumpei Togawa, Yasuhiro Kuwata, Masaki Tatata, Ryota Matsunari, Yuuichi Masuda, Kiyoaki Takeda, Kazuhiko Kotani, Naoki Sakane
  • Organizer: 11th World Stroke Congress
  • Int'l Joint Research
• [Presentation] 高齢者とてんかん (2018)
  • Author(s): 大谷 良
  • Organizer: 京都伏見薬剤師会学術講演会
  • Invited
• [Presentation] Difference for high-density lipoprotein subfractions by non-denaturing polyacrylamide gel electrophoresis in patients with Alzheimer's disease and mild cognitive impairment (2017)
  • Author(s): Ohtani R, Tsuzaki K, Nirengi S, Kotani K, Murase N, Sainouchi M, Kuwata Y, Takata M, Masuda Y, Nakamura M, Sakane N.
  • Organizer: 32nd International Conference of Alzheimer's Disease International
  • Int'l Joint Research
• [Presentation] HDL subclass and inflammation marker in AD and MCI: STOP-Dementia (2017)
  • Author(s): Ohtani R, Nirengi S, Nakamura M, Tsuzaki K, Murase N, Sainouchi M, Kuwata Y, Takata M, Masuda Y, Kotani K, Sakane N.
  • Organizer: Neuroscience 2017
  • Int'l Joint Research
• [Book] 今日の診療のために ガイドライン外来診療 2019 49.認知症 (2019)
  • Author(s): 大谷良 冨本秀和
  • Publisher: 日経メディカル開発
  • ISBN: 4779220084
• [Book] 認知症イメージングテキスト 第１章 認知症総論 ６.治療総論 (2018)
  • Author(s): 大谷良
  • Publisher: 医学書院
  • ISBN: 9784260032315
• [Book] やさしい高次脳機能障害用語事典 認知症：血管性認知症、ビンスワンガー病 (2018)
  • Author(s): 大谷良
  • Publisher: ぱーそん書房
  • ISBN: 4907095481
• [Book] やさしい高次脳機能障害用語事典 遺伝性脳血管障害：CADASIL, CARASIL, HDRS (2018)
  • Author(s): 大谷良
  • Publisher: ぱーそん書房
  • ISBN: 4907095481
• [Book] ガイドライン 外来診療2018年 外来のガイドライン診療 － 診断、管理・治療 － 46 認知症 (2018)
  • Author(s): 大谷 良, 冨本秀和
  • Total Pages: 13
  • Publisher: 日経メディカル開発