Predictive value of biomarkers for the risk of dementia and vascular dementia in patients with vascular risk factors

• Project/Area Number: 15K19227
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Epidemiology and preventive medicine
• Research Institution: Osaka University
• Principal Investigator: Miwa Kaori 大阪大学, 医学部附属病院, 医員 (80645341)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 認知症 / 脳小血管病 / 白質病変 / ホモシステイン / インターロイキン６ / CRP 遺伝多型 / IL6R 遺伝多型 / 脂肪酸 / 認知機能障害 / オメガ脂肪酸 / mild parkinsonian sign / 椎骨動脈径拡大 / 新規バイオマーカー / 国際学会参加 / マトリックスメタロプロティナーゼ / MRI

Outline of Final Research Achievements

We aimed to investigate the predictive value of baseline interleukin-6 (IL-6), C-reactive protein (CRP) and gene variants [IL-6 receptor (IL-6R), rs2228145; IL-6, rs2097677; CRP, rs3093059] for dementia risk in patients with vascular risk factors who are initially cognitively intact. In multivariable analyses adjusted for covariates and IL-6R variant (rs2228145), IL-6 levels for dementia remained significant. Although subjects with rs2228145 carrier had significantly higher IL-6 levels, a significant association between rs2228145 and dementia was not observed. We also explored the predictive value of baseline homocysteine or circulating levels of eicosapentaenoic acid, docosahexaenoic acid [DHA], dihomo-γ-linolenic acid, and arachidonic acid for dementia risk. The effect of IL-6, homocysteine, or DHA for dementia risk remain consistent irrespective of conventional risk factors including apolipoprotein Eε4, cerebral small-vessel disease and brain atrophy.

Research Products

• [Journal Article] Interleukin-6, interleukin-6 receptor gene variant, small-vessel disease and incident dementia (2016)
  • Author(s): Miwa, K. Okazaki, S. Sakaguchi, M. Mochizuki, H. Kitagawa, K.
  • Journal Title: European Journal of Neurology Volume: 23 Issue: 3 Pages: 656-663
  • DOI: 10.1111/ene.12921
  • Peer Reviewed
• [Journal Article] Association between cerebral small vessel diseases and mild parkinsonian signs in the elderly with vascular risk factors. (2016)
  • Author(s): Hatate J, Miwa K, Matsumoto M, Sasaki T, Yagita Y, Sakaguchi M, Kitagawa K, Mochizuki H.
  • Journal Title: Parkinsonism Relat Disord. Volume: Feb 13. pii: S1353-8020(16) Pages: 30039-6
  • DOI: 10.1016/j.parkreldis.2016.02.011
  • Peer Reviewed
• [Journal Article] Increased Total Homocysteine Levels Predict the Risk of Incident Dementia Independent of Cerebral Small-Vessel Diseases and Vascular Risk Factors (2016)
  • Author(s): Miwa, K. Tanaka, M. Okazaki, S. Yagita, Y. Sakaguchi, M. Mochizuki, H. Kitagawa, K.
  • Journal Title: Journal of Alzheimer’s Disease Volume: 49 Issue: 2 Pages: 503-513
  • DOI: 10.3233/jad-150458
  • Peer Reviewed
• [Presentation] 脳小血管病と認知機能低下の縦断的関連 (2017)
  • Author(s): 三輪佳織
  • Organizer: 第42回日本脳卒中学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2017-03-16
• [Presentation] 動脈硬化危険因子を有する症例における脳底動脈径と脳小血管病との 関連 (2017)
  • Author(s): 竹内麻理子
  • Organizer: 第42回日本脳卒中学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2017-03-16
• [Presentation] Long-chain omega-3 polyunsaturated fatty acids, Cerebra l small-vessel disease, and Incident dementia (2016)
  • Author(s): 三輪佳織
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2016-05-18
• [Presentation] Long Chain Polyunsaturated Fatty Acids, Cerebral Small Vessel Disease and Incident Dementia Presentation Time: 6:15pm - 6:45pm (2016)
  • Author(s): Kaori Miwa, Shuhei Okazaki, Manabu Sakaguchi, Hideki Mochizuki, Kazuo Kitagawa
  • Organizer: International stroke conference
  • Place of Presentation: 米国ロサンゼルス
  • Year and Date: 2016-02-17
  • Int'l Joint Research