Amyloid imaging study of the risk of the promotion of Alzheimer's dementia in strok parients

• Project/Area Number: 15K09841
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: National Center for Geriatrics and Gerontology (2017-2018); Nara Medical University (2015-2016)
• Principal Investigator: YASUNO Fumihiko 国立研究開発法人国立長寿医療研究センター, 病院, 医長 (60373388)
• Co-Investigator(Kenkyū-buntansha): 飯田 秀博 国立研究開発法人国立循環器病研究センター, 病院, 非常勤研究員 (30322720) ; 数井 裕光 高知大学, 教育研究部医療学系臨床医学部門, 教授 (30346217) ; 梶本 勝文 大阪大学, 医学系研究科, 特任助教(常勤) (30403067) ; 森田 奈緒美 国立研究開発法人国立循環器病研究センター, 病院, 医師 (70380045)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 脳梗塞 / アミロイドβ / アルツハイマー型認知症 / ポジトロンCT / アミロイドイメージング / 教育歴 / MRI / PET アミロイド検査 / PETアミロイド検査 / ＭＲＩ / ＰＥＴ / アミロイド定量 / リンパ球系幹細胞

Outline of Final Research Achievements

A direct causal relationship of cerebrovascular risk factors/stroke to amyloid β (Aβ) deposition has yet to be shown. We conducted [11C] Pittsburgh Compound B (PiB)-PET positron emission tomography (PET) analysis on subacute ischemic stroke patients and healthy controls. We tested the hypothesis that subacute ischemic stroke patients would show focal Aβ accumulation in cortical regions, which would increase and extend over time during the chronic phase after stroke onset. We found that the onset of ischemic stroke may trigger Aβ deposition in the precuneus / posterior cingulate cortex (PCu/PCC), whereby amyloid deposition begins at an early stage of Alzheimer’s disease (AD). Our findings support the existence of a cooperative association between vascular risk factors/stroke and AD progression. Further, we found that educational achievement had a protective effect against the increase in Aβ accumulation.

Academic Significance and Societal Importance of the Research Achievements

これまでに、脳梗塞発症直後から、アミロイドイメージングを用い、横断的かつ継時的にAβ集積を検証した報告はない。本研究はADの早期から変性病理過程が生ずる楔前部/後部帯状回領域で、脳梗塞患者のアミロイドβの集積がみられることを明らかにし、脳梗塞がAD病理の促進因子であることを客観的に示した。 また、本研究は教育年数の長さがアミロイドβ集積に対して抑止的に働くことを明らかにし、人生早期段階の教育に関連した神経メカニズムが脳梗塞後のAD発症リスクの低減につながる可能性を示した。我々の結果は脳血管障害患者の効果的な AD 予防・治療を考えるうえで有用であると考えられる。

Research Products

• [Journal Article] Detection of brain amyloid-β deposits due to the repetitive head trauma in a former karate player (2019)
  • Author(s): Takahashi M, Yasuno F, Yamamuro K, et al.
  • Journal Title: Psychogeriatrics Volume: 19 Issue: 3 Pages: 276-281
  • DOI: 10.1111/psyg.12383
  • Peer Reviewed
• [Journal Article] Dendrite Complexity of the Posterior Cingulate Cortex as a Substrate for Recovery from Post-stroke Depression: A Pilot Study (2019)
  • Author(s): Yasuno F, Ando D, Yamamoto A, et al.
  • Journal Title: Psychiatry Research: Neuroimaging Volume: 287 Pages: 49-55
  • DOI: 10.1016/j.pscychresns.2019.01.015
  • Peer Reviewed
• [Journal Article] Decreased perfusion of the posterior cingulate gyri shown by a cingulate island score is a possible marker of vulnerability to behavioural and psychological symptoms of Alzheimer's disease: a pilot study. (2019)
  • Author(s): Yasuno F, Matsuoka K, Miyasaka T, et al.
  • Journal Title: Psychogeriatrics Volume: 19 Issue: 2 Pages: 165-170
  • DOI: 10.1111/psyg.12379
  • Peer Reviewed
• [Journal Article] Left dorsolateral prefrontal cortex atrophy is associated with frontal lobe function in Alzheimer's disease and contributes to caregiver burden. (2018)
  • Author(s): Matsuoka K, Yasuno F, Hashimoto A, et al.
  • Journal Title: Int J Geriatr Psychiatry Volume: 33 Issue: 5 Pages: 703-709
  • DOI: 10.1002/gps.4843
  • Peer Reviewed
• [Journal Article] Mutual effect of cerebral amyloid β and peripheral lymphocytes in cognitively normal older individuals (2017)
  • Author(s): Yasuno F, Kazui H, Kajimoto K, Ihara M, Morita N, Taguchi A, Yamamoto A, Matsuoka K, Takahashi M, Nakagawara J, Tsuji M, Iida H, Kishimoto T, Nagatsuka K
  • Journal Title: Int J Geriatr Psychiatry Volume: 32 Issue: 12
  • DOI: 10.1002/gps.4660
  • Peer Reviewed
• [Journal Article] Significant correlation between openness personality in normal subjects and brain myelin mapping with T1/T2-weighted MR imaging. (2017)
  • Author(s): Yasuno F, Kudo T, Yamamoto A, Matsuoka K, Takahashi M, Iida H, Ihara M, Nagatsuka K, Kishimoto T.
  • Journal Title: Heliyon Volume: 3 Issue: 9 Pages: e00411-e00411
  • DOI: 10.1016/j.heliyon.2017.e00411
  • Peer Reviewed / Open Access
• [Journal Article] Microstructural Differences in the Corpus Callosum in Patients With Bipolar Disorder and Major Depressive Disorder. (2017)
  • Author(s): Matsuoka K, Yasuno F, Kishimoto T, Yamamoto A, Kiuchi K, Kosaka J, Nagatsuka K, Iida H, Kudo T.
  • Journal Title: J Clin Psychiatry. Volume: 78 Pages: 99-104
  • Peer Reviewed
• [Journal Article] High amyloid-β deposition related to depressive symptoms in older individuals with normal cognition: A pilot study (2016)
  • Author(s): Yasuno F, Kazui H, Morita N, Kajimoto K, Ihara M, Taguchi A, Yamamoto A, Matsuoka K, Kosaka J, Kudo T, Iida H, Kishimoto T, Nagatsuka K
  • Journal Title: Int J Geriatr Psychiatry Volume: 31 Issue: 8 Pages: 920-928
  • DOI: 10.1002/gps.4409
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Use of T1-weighted/T2-weighted magnetic resonance ratio to elucidate changes due to amyloid-β accumulation in cognitively normal subjects. (2016)
  • Author(s): Yasuno F, Kazui H, Morita N, Kajimoto K, Ihara M, Taguchi A, Yamamoto A, Matsuoka K, Takahashi M, Nakagawara J, Iida H, Kishimoto T, Nagatsuka K
  • Journal Title: Neuroimage Clin Volume: 13 Pages: 209-214
  • DOI: 10.1016/j.nicl.2016.11.029
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Delayed atrophy in posterior cingulate cortex and apathy after stroke. (2015)
  • Author(s): MatsuokaMatsuoka K, Yasuno F, Taguchi A, Yamamoto A, Kajimoto K, Kazui H, Kudo T, Sekiyama A, Kitamura S, Kiuchi K, Kosaka J, Kishimoto T, Iida H, Nagatsuka K
  • Journal Title: Int J Geriatr Psychiatry Volume: 30 Issue: 6 Pages: 566-572
  • DOI: 10.1002/gps.4185
  • Peer Reviewed
• [Journal Article] Resting-state synchrony between the retrosplenial cortex and anterior medial cortical structures relates to memory complaints in subjective cognitive impairment (2015)
  • Author(s): Yasuno F, Kazui H, Yamamoto A et al
  • Journal Title: Neurobiol Aging Volume: 36 Issue: 6 Pages: 2145-52
  • DOI: 10.1016/j.neurobiolaging.2015.03.006
  • Peer Reviewed
• [Journal Article] A structural model of age, grey matter volumes, education, and personality traits. (2015)
  • Author(s): Kitamura S, Yasuno F, Yamamoto A, Kazui H, Kudo T, Matsuoka K, Kiuchi K, Kosaka J, Nagatsuka K, Iida H, Kishimoto T.
  • Journal Title: Psychogeriatrics. Volume: 15 Issue: 1 Pages: 1-8
  • DOI: 10.1111/psyg.12118
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Microstructural abnormality in white matter, regulatory T lymphocytes, and depressive symptoms after stroke. (2014)
  • Author(s): Yasuno F, Taguchi A, Yamamoto A, Kajimoto K, Kazui H, Kudo T, Kikuchi-Taura A, Sekiyama A, Kishimoto T, Iida H, Nagatsuka K.
  • Journal Title: Psychogeriatrics Volume: 14 Issue: 9 Pages: 213-21
  • DOI: 10.1002/gps.4235
  • Peer Reviewed
• [Presentation] 環境と認知症：アミロイド/タウイメージングからの視点 (2019)
  • Author(s): 安野史彦
  • Organizer: 日本生物学的精神医学会
• [Presentation] Dendrite Complexity of the Posterior Cingulate Cortex as a Substrate for Recovery from Post-stroke Depression: a pilot study (2019)
  • Author(s): 安野史彦, 安藤大輔、山本明秀ら
  • Organizer: 日本生物学的精神医学会
• [Presentation] 脳梗塞患者のアミロイドβ集積と、その抑制因子に関する検討 (2019)
  • Author(s): 南博之、安野史彦、梶本勝文ら
  • Organizer: 日本老年精神医学会
• [Presentation] 後部帯状回の神経樹状突起の可塑性と脳梗塞後のうつ状態からの回復との関連について (2019)
  • Author(s): 南ひかる、安野史彦、安藤大輔ら
  • Organizer: 日本老年精神医学会
• [Presentation] 帯状回島兆候に基づく認知症患者の精神行動障害の脆弱性評価可能性について (2018)
  • Author(s): 安野史彦
  • Organizer: 日本生物学的精神医学会
• [Presentation] 帯状回島兆候： 疾患鑑別から症状発現予測可能性まで (2018)
  • Author(s): 安野史彦
  • Organizer: 日本認知症学会学術総会
• [Presentation] MRI-T1w/T2w比を用いたアミロイドβ集積による病理的変化の検出可能性 (2017)
  • Author(s): 安野 史彦, 数井 裕光, 梶本 勝文, 猪原 匡史, 山本 明秀, 松岡 究, 高橋 誠人, 紀本 創兵, 中川原 譲二, 飯田 秀博, 長束 一行, 岸本 年史
  • Organizer: 第32回日本老年精神医学会
• [Presentation] MRI-T1w/T2w比を用いたアミロイドβ集積による病理的変化の検出可能性 (2017)
  • Author(s): 安野 史彦, 数井 裕光, 梶本 勝文, 猪原 匡史, 山本 明秀, 松岡 究, 高橋 誠人, 紀本 創兵, 中川原 譲二, 飯田 秀博, 長束 一行, 岸本 年史
  • Organizer: 第59回日本老年医学会
• [Presentation] 脳神経画像医学が認知症臨床にもたらすもの (2017)
  • Author(s): 安野史彦
  • Organizer: 第3２回老年精神医学会
  • Invited
• [Presentation] Early detection of Amyloid deposition in a 30-year-old patient with repetitive mild head trauma (2017)
  • Author(s): Masato Takahashi, Kazuhiko Yamamuro, Fumihiko Yasuno, Kiwamu Matsuoka, Soichiro Kitamura, Hiroaki Yoshikawa, Akihide Yamamoto, Hidehiro Iida, Tetsyuta Fukuda, Masafumi Ihara, Kazuyuki Nagatsuka, Toshifumi Kishimoto
  • Organizer: International Psychogeriatric Association International Congress
  • Int'l Joint Research
• [Presentation] 認知機能正常な健常老齢者における脳内アミロイドβ集積と、末梢血リンパ球の相互の影響 (2016)
  • Author(s): 安野 史彦, 数井 裕光, 森田 奈緒美, 梶本 勝文, 猪原 匡史, 田口 明彦, 山本 明秀, 松岡 究, 小坂 淳, 工藤 喬, 飯田 秀博, 長束 一行, 岸本 年史
  • Organizer: 第38回日本生物学的精神医学会
  • Place of Presentation: 福岡
  • Year and Date: 2016-09-08
• [Presentation] 認知機能正常な老齢者において高いアミロイドβ集積は抑うつ症状に関連する (2016)
  • Author(s): 安野 史彦, 数井 裕光, 森田 奈緒美, 梶本 勝文, 猪原 匡史, 田口 明彦, 山本 明秀, 松岡 究, 小坂 淳, 工藤 喬, 飯田 秀博, 長束 一行, 岸本 年史
  • Organizer: 第31回日本老年精神医学会
  • Place of Presentation: 金沢
  • Year and Date: 2016-06-23
• [Presentation] Resting -state synchrony between the retrosplenial cortex and anterior medial cortical structures relates to memory complaints in subjective cognitive impairment (2015)
  • Author(s): Yasuno F, Kazui H, Yamamoto A, et al
  • Organizer: International Psychogeriatric Association International Congress
  • Place of Presentation: Berlin
  • Year and Date: 2015-10-13
  • Int'l Joint Research
• [Presentation] 主観的記憶障害者の後部脳梁膨大皮質と脳前方部内側皮質領域の安静時fMRIにおける非協調性について (2015)
  • Author(s): 安野 史彦, 数井 裕光, 山本 明秀 ら
  • Organizer: 第37回日本生物学的精神医学会・第45回日本神経精神薬理学会合同年会
  • Place of Presentation: 東京
  • Year and Date: 2015-09-24
• [Presentation] 健常老齢者における高い教育水準と低いアミロイドβ集積について (2015)
  • Author(s): 安野 史彦, 数井 裕光, 森田 奈緒美 ら
  • Organizer: 第30回日本老年精神医学会
  • Place of Presentation: 横浜
  • Year and Date: 2015-06-12
• [Presentation] 脳梗塞後の白質微小構造変化と、調節性T細胞およびうつ症状との関連 (2015)
  • Author(s): 安野 史彦, 數井 裕光, 田口 明彦 ら
  • Organizer: 第111回日本精神神経学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-06-04