The prospective study about association between mid-regional proadrenomedullin levels and progression of deep white matter lesions in the brain accompanying vascular cognitive decline

• Project/Area Number: 15K08812
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hygiene and public health
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Kuriyama Nagato 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (60405264)
• Co-Investigator(Kenkyū-buntansha): 渡辺 能行 京都府立医科大学, 医学(系)研究科(研究院), 教授 (00191809) ; 尾崎 悦子 京都府立医科大学, 医学(系)研究科(研究院), 助教 (00438219)
• Research Collaborator: Mizuno Toshiki 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30264782) ; Yamada Kei 京都府立医科大学, 医学(系)研究科(研究院), 教授 (80315960) ; Kondo Masaki 京都府立医科大学, 医学(系)研究科(研究院), 講師 (20315964) ; Toyama Teruhide 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40711362) ; Matsui Daisuke 京都府立医科大学, 医学(系)研究科(研究院), 助教 (20613566) ; Watanabe Isao 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10636525)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 軽度認知機能障害 / 血管作動性物質アドレノデュリン / 頭部MRI検査 / 虚血性深部白質病変 / 長期追跡調査 / 血管作動性物質ア ドレノ メ / 頭部MRI 検査 / 虚血性深部 白 質病変 / 血管作動性物質アドレノメヂュリン / 追跡調査

Outline of Final Research Achievements

Adrenomedullin (ADM) is a vasoreactive physiological peptide.　To investigate　mid-regional proADM (MR-proADM), a stable fragment of the ADM precursor, and cerebral deep white matter lesions (DWMLs) in association with cognitive decline. The study participants were 288 patients (194 men, 70.8 y.o.) . The Fazekas classification system (Grade :G0 [normal] to G3 [severe]) was used for the evaluation of DWMLs on brain MRI.
MR-proADM levels significantly increased with DWML grade progression.The odds ratio for high MR-proADM levels was 1.73 in the groups graded G2 and G3 on brain MRI. MR-proADM levels were increased in the G3 group in 2013 compared with 2008.
MR-proADM levels were significantly different between the DWML groups and inversely correlated with cognitive function test scores、suggesting that high MR-proADM levels and DWMLs are associated with cognitive decline.The MR-proADM level may be an effective candidate as a potential diagnostic surrogate marker of cognitive decline.

Academic Significance and Societal Importance of the Research Achievements

今回の研究成果から、ヒトプロアドレノメデュリン（MR-proADM）測定が、血管性認知症の病態と進行を把握できる生物学的マーカーである可能性が明らかとなった。マウスの基礎実験では、アドレノメデュリン投与により、脳内白質保護と認知機能回復の可能性が示されている。以上より、脳機能保護候補因子であるMR-proADMは、認知機能低下群における鋭敏な予知マーカーとして有用であると考えられる。
認知症への対応が社会問題化している現在、認知症の早期予知・診断マーカーとして、学術的に注目される研究成果である。我々は、国内での検査体制の確立と臨床応用の準備を進めており、社会的意義は十分期待できる結果を得た。

Research Products

• [Journal Article] Association between mid-regional proadrenomedullin levels and progression of deep white matter lesions in the brain accompanying cognitive decline. (2017)
  • Author(s): Kuriyama N, Ihara M, Mizuno T, Ozaki E, Matsui D, Watanabe I, Koyama T, Kondo M, Tokuda T, Tamura A, Yamada K, Akazawa K, Takeda K, Takada A, Mizuno S, Nakagawa M, Watanabe Y.
  • Journal Title: J Alzheimers Dis Volume: 56 Issue: 4 Pages: 1253-1262
  • DOI: 10.3233/jad-160901
  • Peer Reviewed
• [Journal Article] 脳血管から見た血管作動性生理ペプチドの新しい役割と脳内深部白質病変 (2016)
  • Author(s): 小山晃英、 渡辺能行、 栗山長門
  • Journal Title: 神経内科 Volume: ８４ Pages: 550-556
  • Peer Reviewed
• [Journal Article] 脳血管から見た血管作動性生理ペプチドの新しい役割と脳内深部白質病変 (2016)
  • Author(s): 小山晃英、渡辺能行、栗山長門
  • Journal Title: 神経内科（印刷中） Volume: ８４巻第６号
  • Peer Reviewed
• [Presentation] Mid-regional pro-adrenomedullin levels are associated with progression of deep white matter lesions in the brain accompanying cognitive decline. (2018)
  • Author(s): Kuriyama N, Koyama T, Ihara M, Mizuno T, Ozaki E, Matsui D, Watanabe I, Kondo M, Tokuda T, Tamura A, Yamada K, Akazawa K,Takeda K, Takada A, Mizuno S, Nakagawa M, Watanabe Y.
  • Organizer: The 21st International Epidemiological Association (IEA) World Congress of Epidemiology (WCE2017).
  • Int'l Joint Research
• [Presentation] Vasoactive mid-regional pro-adrenomedullin is associated with cognitive decline accompanying deep white matter lesions in the brain: a cross-sectional brain MRI study. (2018)
  • Author(s): Kuriyama N, Koyama T, Ihara M, Mizuno T, Ozaki E, Matsui D, Watanabe I, Kondo M, Tokuda T, Tamura A, Yamada K, Akazawa K,Takeda K, Takada A, Mizuno S, Nakagawa M, Watanabe Y.
  • Organizer: XXIII World Congress of Neurology.
  • Int'l Joint Research
• [Presentation] Mid-regional pro-adrenomedullin levels are associated with progression of deep white matter lesions in the brain accompanying cognitive decline. (2017)
  • Author(s): Kuriyama N, Koyama T, Ihara M, Mizuno T, Ozaki E, Matsui D, Watanabe I, Kondo M, Tokuda T, Tamura A, Yamada K, Akazawa K, Takeda K, Takada A, Mizuno S, Nakagawa M, Watanabe Y.
  • Organizer: The 21st International Epidemiological Association (IEA) World Congress of Epidemiology (WCE2017).
  • Int'l Joint Research
• [Presentation] Vasoactive mid-regional pro-adrenomedullin is associated with cognitive decline accompanying deep white matter lesions in the brain: a cross-sectional brain MRI study. (2017)
  • Author(s): Kuriyama N, Koyama T, Ihara M, Mizuno T, Ozaki E, Matsui D, Watanabe I, Kondo M, Tokuda T, Tamura A, Yamada K, Akazawa K, Takeda K, Takada A, Mizuno S, Nakagawa M, Watanabe Y.
  • Organizer: XXIII World Congress of Neurology.
  • Int'l Joint Research
• [Remarks] 血管性認知症に関する疫学研究
  • URL: http://www.f.kpu-m.ac.jp/k/jkpum/pdf/127/127-7/127-7-01kuriyama.pdf
• [Remarks] 地域保健医療疫学
  • URL: http://www.f.kpu-m.ac.jp/k/jkpum/pdf/122/122-3/bumon03.pdf