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パーキンソン病に伴う認知症の早期診断モデル構築と個別化医療への展開

Research Project

Project/Area Number 22K07520
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionNagoya City University

Principal Investigator

打田 佑人  名古屋市立大学, 医薬学総合研究院(医学), 研究員 (20834261)

Project Period (FY) 2022-04-01 – 2026-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2025: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2024: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsパーキンソン病 / 認知症 / MRI / QSM / 機械学習 / 血液脳関門 / 認知機能障害
Outline of Research at the Start

2019年度-2021年度の研究において、パーキンソン病を対象とした臨床画像研究により、脳内磁化率変化を定量的に計測することのできるQSMが、パーキンソン病に伴う認知機能障害の客観的バイオマーカーとして有用であることを明らかにした。一方で、個々の責任病巣・表現型は多様性を示すことから、集団を対象とした探索的解析や関心領域のみに基づいた従前の統計解析では、早期診断ツールとして活用する際に診断困難例が少なからず存在することが課題であった。2022年度より着手する本研究では、臨床情報に紐付いた全脳の磁化率変化を個別に登録し、機械学習による個別化医療への展開を念頭に置いた早期診断モデルの構築を目指す。

Outline of Annual Research Achievements

本研究は,臨床所見やMRIから得られる各種情報を組み合わせて、パーキンソン病に伴う認知症の早期診断モデル構築と個別化医療への展開を目指すものである。2023年度からの本研究では、定量的磁化率画像(Quantitative susceptibility mapping)とR2* relaxometry mapの画像情報から鉄と髄鞘を分離して評価する方法を開発し、個別化医療への展開を念頭に予後予測モデルを作成して臨床応用を試みた。得られた成果としては、全脳解析により白質の髄鞘障害と認知機能障害の関係を見出し(Front Neurol. 2023;14:1251230.)、さらに、これらの画像バイオマーカーを用いた縦断解析により神経学的予後との関係を明らかにした(Stroke. 2024;55(4):1041-1050.)。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

パーキンソン病に伴う認知症の早期診断モデル構築と個別化医療への展開,その臨床応用を目指す本研究において,着実に研究成果を報告できており,研究計画は順調に進展していると言える.

Strategy for Future Research Activity

今後の推進方策について、血液脳関門と脳内鉄動態の関連についてMRIを画像バイオマーカーとして研究を進めていく予定である。認知機能障害と脳内鉄沈着との関係において、血液脳関門が果たす機能的役割の関与は大きい。次に計画する研究のステップとして、血液脳関門と脳内鉄動態の関連に着目して、総説に纏めた(Front Aging Neurosci. 2023;15:1111448.)。

Report

(2 results)
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (12 results)

All 2024 2023 2022 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] Johns Hopkins University(米国)

    • Related Report
      2022 Research-status Report
  • [Journal Article] Longitudinal Changes in Iron and Myelination Within Ischemic Lesions Associate With Neurological Outcomes: A Pilot Study2024

    • Author(s)
      Yuto Uchida, Hirohito Kan, Yuya Kano, Kengo Onda, Keita Sakurai, Koji Takada, Yoshino Ueki, Noriyuki Matsukawa Argye E Hillis, Kenichi Oishi
    • Journal Title

      Stroke

      Volume: 55 Issue: 4 Pages: 1041-1050

    • DOI

      10.1161/strokeaha.123.044606

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Assessing white matter microstructural changes in idiopathic normal pressure hydrocephalus using voxel-based R2* relaxometry analysis2023

    • Author(s)
      Kano Yuya、Uchida Yuto、Kan Hirohito、Sakurai Keita、Kobayashi Susumu、Seko Kento、Mizutani Keisuke、Usami Toshihiko、Takada Koji、Matsukawa Noriyuki
    • Journal Title

      Frontiers in Neurology

      Volume: 14 Pages: 1251230-1251230

    • DOI

      10.3389/fneur.2023.1251230

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Contributions of blood?brain barrier imaging to neurovascular unit pathophysiology of Alzheimer’s disease and related dementias2023

    • Author(s)
      Uchida Yuto、Kan Hirohito、Sakurai Keita、Oishi Kenichi、Matsukawa Noriyuki
    • Journal Title

      Frontiers in Aging Neuroscience

      Volume: 15 Pages: 1111448-1111448

    • DOI

      10.3389/fnagi.2023.1111448

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Machine learning trained with quantitative susceptibility mapping to detect mild cognitive impairment in Parkinson's disease2022

    • Author(s)
      Shibata Haruto、Uchida Yuto、Inui Shohei、Kan Hirohito、Sakurai Keita、Oishi Naoya、Ueki Yoshino、Oishi Kenichi、Matsukawa Noriyuki
    • Journal Title

      Parkinsonism and Related Disorders

      Volume: 94 Pages: 104-110

    • DOI

      10.1016/j.parkreldis.2021.12.004

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] R2* relaxometry analysis for mapping of white matter alteration in Parkinson’s disease with mild cognitive impairment2022

    • Author(s)
      Kan Hirohito、Uchida Yuto、Ueki Yoshino、Arai Nobuyuki、Tsubokura Satoshi、Kunitomo Hiroshi、Kasai Harumasa、Aoyama Kiminori、Matsukawa Noriyuki、Shibamoto Yuta
    • Journal Title

      NeuroImage: Clinical

      Volume: 33 Pages: 102938-102938

    • DOI

      10.1016/j.nicl.2022.102938

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinicoradiological Features in Progressive Supranuclear Palsy Comorbid with Argyrophilic Grains2022

    • Author(s)
      Sakurai Keita、Kaneda Daita、Morimoto Satoru、Uchida Yuto、Inui Shohei、Kimura Yasuyuki、Kato Takashi、Ito Kengo、Hashizume Yoshio
    • Journal Title

      Movement Disorders Clinical Practice

      Volume: 9 Issue: 4 Pages: 484-488

    • DOI

      10.1002/mdc3.13455

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] APOE e4 dose associates with increased brain iron and β-amyloid via blood-brain barrier dysfunction2022

    • Author(s)
      Yuto Uchida, Hirohito Kan, Keita Sakurai, Yoshihiko Horimoto, Emi Hayashi, Akihiko Iida, Nobuyuki Okamura, Kenichi Oishi, Noriyuki Matsukawa
    • Journal Title

      J Neurol Neurosurg Psychiatry

      Volume: - Issue: 7 Pages: 772-778

    • DOI

      10.1136/jnnp-2021-328519

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Quantitative susceptibility mapping as an imaging biomarker for Alzheimer’s disease: The expectations and limitations2022

    • Author(s)
      Uchida Yuto、Kan Hirohito、Sakurai Keita、Oishi Kenichi、Matsukawa Noriyuki
    • Journal Title

      Frontiers in Neuroscience

      Volume: 16

    • DOI

      10.3389/fnins.2022.938092

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Presentation] Microstructural neurodegeneration of the entorhinal-hippocampus pathway in preclinical Alzheimer's disease: ex vivo 11.7T MRI and histology2023

    • Author(s)
      Yuto Uchida
    • Organizer
      International Society for Magnetic Resonance in Medicine 2023
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research
  • [Presentation] Blood-brain barrier function associates with brain iron dynamics along developmental trajectory: a combined quantitative magnetic resonance imaging study during childhood2023

    • Author(s)
      Yuto Uchida
    • Organizer
      American Neurological Association 2023
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research
  • [Presentation] Machine learning trained with multi-atlas QSM to detect cognitive decline in Parkinson’s disease2022

    • Author(s)
      柴田治人
    • Organizer
      2022年第63回日本神経学会学術大会
    • Related Report
      2022 Research-status Report

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Published: 2022-04-19   Modified: 2024-12-25  

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