Establishing Parkinson's disease registry focusing on advanced MRI as a surrogate marker

• Project/Area Number: 21K20698
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0704:Neuroscience, brain sciences, and related fields
• Research Institution: Juntendo University
• Principal Investigator: Takeshige-Amano Haruka 順天堂大学, 医学部, 助教 (00906076)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: パーキンソン病 / レジストリ / 先進的拡散MRI / 衝動制御障害 / セレギリン / 白質微小構造 / 先進的ＭＲＩ / データベース / MAOB阻害薬

Outline of Research at the Start

パーキンソン病（PD）ではこれまで脳のCTやMRIで変化が認められないとされてきたが、先進的MRIを用いて微細構造を解析することで様々な変化が明らかになっている。本研究では先進的MRIを用いて、症状や使用薬剤による、主に大脳白質の微細構造の違いを比較し、各種症状の病態解明や、適切な治療選択を目指す。そのために多数のPD患者より、先進的MRIをはじめとする画像検査、心理検査、血液検査および症状のデータを長期間・定期的に収集し、これらの多角的データが紐付けされたデータベースを構築する。

Outline of Final Research Achievements

Parkinson's disease (PD) registry, the main project, has been established to have annual evaluation including clinical scores taken by medical doctors, psychologists, and questionnaires, as well as blood samples and advanced MRI. At the end of 2022, it holds 812 registry, with 312 longitudinal cases, 508 blood samples, and 513 advanced MRI data.
Based on this database, the relationship between impulsive compulsive behaviors and cerebral white matter microstructure change was detected, and the result was published on Annals of Clinical and Translational Neurology (IF=5.43). Also, another study on the white matter microstructure difference between PD patients with and without selegiline treatment was conducted and presented at several congresses and submitted to a journal..

Academic Significance and Societal Importance of the Research Achievements

PDデータベースに基づき様々な研究を展開することが可能となった。
衝動制御障害を有するPD患者で特定の白質経路の微小構造変化が抑制されていることを見いだした。この白質微小構造が保たれている患者に、衝動制御障害のリスク因子であるドパミンアゴニストを使用することで衝動制御障害が誘発されやすいことも予想され、テーラーメイド医療につながる成果と考える。また特定の白質経路における病的な微小構造の変化がセレギリン内服患者では抑制されている可能性を示唆する結果も得た。セレギリンの効果を示す新たな所見であり、既存のPD治療を前進させる成果と言える。

Research Products

• [Journal Article] Analytical and clinical validity of wearable, multi-sensor technology for assessment of motor function in patients with Parkinson's disease in Japan (2023)
  • Author(s): G Oyama, M Burq, T Hatano, W J Marks Jr, R Kapur, J Fernandez, K Fujikawa, Y Furusawa, K Nakatome, E Rainaldi, C Chen, K Chung Ho, T Ogawa, H Kamo, Y Oji, H Takeshige-Amano, D Taniguchi, R Nakamura, F Sasaki, S Ueno, K Shiina, A Hattori, N Nishikawa, M Ishiguro, S Saiki, A Hayashi, M Motohashi, N Hattori
  • Journal Title: Scientific Report Volume: 13-1 Issue: 1 Pages: 3600-3600
  • DOI: 10.1038/s41598-023-29382-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Investigating the efficacy and safety of elobixibat, an ileal bile acid transporter inhibitor, in patients with Parkinson’s disease with chronic constipation: a multicentre, placebo-controlled, randomised, double-blind, parallel-group study (CONST-PD) (2022)
  • Author(s): Taku Hatano, Genko Oyama, Yasushi Shimo, Kotaro Ogaki, Noriko Nishikawa, Jiro Fukae, Ryota Nakamura, Naohide Kurita, Taiji Tsunemi, Yutaka Oji, Shinji Saiki, Kenya Nishioka, Haruka Takeshige-Amano, et al.
  • Journal Title: BMJ Open Volume: 12 Issue: 2 Pages: e054129-e054129
  • DOI: 10.1136/bmjopen-2021-054129
  • Peer Reviewed / Open Access
• [Journal Article] White matter microstructures in Parkinson's disease with and without impulse control behaviors (2022)
  • Author(s): Takeshige‐Amano Haruka、Hatano Taku、Kamagata Koji、Andica Christina、Uchida Wataru、Abe Masahiro、Ogawa Takashi、Shimo Yasushi、Oyama Genko、Umemura Atsushi、Ito Masanobu、Hori Masaaki、Aoki Shigeki、Hattori Nobutaka
  • Journal Title: Annals of Clinical and Translational Neurology Volume: 9 Issue: 3 Pages: 253-263
  • DOI: 10.1002/acn3.51504
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] White matter and nigral alterations in multiple system atrophy-parkinsonian type (2021)
  • Author(s): Ogawa Takashi、Hatano Taku、Kamagata Koji、Andica Christina、Takeshige-Amano Haruka、Uchida Wataru、Kamiyama Daiki、Shimo Yasushi、Oyama Genko、Umemura Atsushi、Iwamuro Hirokazu、Ito Masanobu、Hori Masaaki、Aoki Shigeki、Hattori Nobutaka
  • Journal Title: npj Parkinson's Disease Volume: 7 Issue: 1 Pages: 1-12
  • DOI: 10.1038/s41531-021-00236-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] White matter alterations in Parkinson's disease with levodopa-induced dyskinesia (2021)
  • Author(s): Ogawa Takashi、Hatano Taku、Kamagata Koji、Andica Christina、Takeshige-Amano Haruka、Uchida Wataru、Saito Yuya、Shimo Yasushi、Oyama Genko、Umemura Atsushi、Iwamuro Hirokazu、Ito Masanobu、Hori Masaaki、Aoki Shigeki、Hattori Nobutaka
  • Journal Title: Parkinsonism & Related Disorders Volume: 90 Pages: 8-14
  • DOI: 10.1016/j.parkreldis.2021.07.021
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] セレギリン投与有無によるパーキンソン病患者の大脳白質微小構造の差 (2023)
  • Author(s): 竹重遥香、波田野琢、小川崇、進藤淳彦、大山彦光、下泰司、服部信孝
  • Organizer: 第１２０回日本内科学会総会
• [Presentation] セレギリンの長期投与はパーキンソン病患者の白質微小構造変化を抑制する (2022)
  • Author(s): 竹重遥香， 波田野琢， 鎌形康司， Andica Christina， 小川崇，進藤淳彦, 下泰司， 大山彦光， 梅村淳， 伊藤賢伸， 堀正明， 青木茂樹， 服部信孝
  • Organizer: 第16回パーキンソン病・運動障害疾患コングレス
• [Presentation] Chronic selegiline treatment suppresses white matter neuroinflammation in Parkinson’s disease patients. (2021)
  • Author(s): Haruka Takeshige-Amano
  • Organizer: 日本神経学会総会