Study on very early diagnosis of dementia by connective analysis of the brain based on graph theory

• Project/Area Number: 18K07779
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Southen Tohoku Research Institute for Neuroscience (2020); National Center of Neurology and Psychiatry (2018-2019)
• Principal Investigator: Matsuda Hiroshi 一般財団法人脳神経疾患研究所, 南東北創薬・サイクロトロン研究センター, 院長 (90173848)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 認知症 / MRI / ネットワーク / アルツハイマー病 / PET / 脳内結合 / アミロイド / タウ / 脳内結合性

Outline of Final Research Achievements

Local network measurements associated with tau protein accumulation were examined using structural network analysis with MRI 3D T1-weighted images based on graph theory using gray matter similarity between healthy elderly and Alzheimer's disease patients. As a result, the amyloid β protein-negative healthy elderly group showed a significant positive correlation with tau protein accumulation, while the amyloid β protein-positive Alzheimer's disease patient group showed a significant negative correlation. Tau protein accumulation in the healthy elderly group was most correlated in the caudate nucleus.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病（AD）は、細胞外アミロイド-βプラークと過剰リン酸化タウで構成される細胞内神経原線維変化の存在によって特徴付けられる。これらのタンパク質は局所シナプス破壊に関連しているため、ADは局所シナプス機能不全を伴う切断症候群とみなすことができる。機能的磁気共鳴画像法などいくつかの神経画像診断法を使用してグラフ理論解析などにより、ADの脳ネットワーク研究が行われているがその結果は首尾一貫していない。本研究では生理的影響を受けにくく普遍性の高いT1強調イメージングを使用した構造ネットワーク解析によりADでのネットワーク異常の検出が可能であることを明らかにした。

Research Products

• [Journal Article] Gray matter structural networks related to 18 F-THK5351 retention in cognitively normal older adults and Alzheimer's disease patients (2021)
  • Author(s): Yoko Shigemoto, Daichi Sone, Kyoji Okita, Norihide Maikusa, Tensho Yamao, Yukio Kimura, Fumio Suzuki, Hiroyuki Fujii, Koichi Kato, Noriko Sato, Hiroshi Matsuda
  • Journal Title: eNeurologicalSci Volume: 22 Pages: 100309-100309
  • DOI: 10.1016/j.ensci.2021.100309
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association between neurite metrics and tau/inflammatory pathology in Alzheimer’s disease (2020)
  • Author(s): Sone D, Shigemoto Y, Ogawa M, Maikusa N, Okita K, Takano H, Kato K, Sato N, Matsuda H
  • Journal Title: Alzheimers Dement (Amst) Volume: 12 Issue: 1
  • DOI: 10.1002/dad2.12125
  • Peer Reviewed / Open Access
• [Journal Article] Voxel-based correlation of 18F-THK5351 accumulation and gray matter volume in the brain of cognitively normal older adults. (2019)
  • Author(s): Shigemoto Y, Sone D, Ota M, Maikusa N, Ogawa M, Okita K, Takano H, Kato K, Kimura Y, Morimoto E, Suzuki F, Fujii H, Sato N, Matsuda H
  • Journal Title: EJNMMI Res Volume: 9 Issue: 1 Pages: 81-81
  • DOI: 10.1186/s13550-019-0552-3
  • NAID: 120007127795
  • Peer Reviewed / Open Access
• [Journal Article] Longitudinal analysis of risk factors for dementia based on Mild Cognitive Impairment Screen results and questionnaire responses from healthy Japanese individuals registered in an online database. (2019)
  • Author(s): Ogawa M, Maruo K, Sone D, Shimada H, Suzuki K, Watanabe H, Matsuda H, Mizusawa H
  • Journal Title: Alzheimers Dement (N Y) Volume: 5 Issue: 1 Pages: 347-353
  • DOI: 10.1016/j.trci.2019.06.003
  • Peer Reviewed / Open Access
• [Journal Article] Differentiation Between Dementia With Lewy Bodies And Alzheimer’s Disease Using Voxel-Based Morphometry Of Structural MRI: A Multicenter Study (2019)
  • Author(s): Matsuda H, Yokoyama K, Sato N, Ito K, Nemoto K, Oba H, Hanyu H, Kanetaka H, Mizumura S, Kitamura S, Shinotoh H, Shimada H, Suhara T, Terada H, Nakatsuka T, Kawakatsu S, Hayashi H, Asada T, Ono T, Goto T, Shigemori K
  • Journal Title: Neuropsychiatric Disease and Treatment Volume: 15 Pages: 2715-2722
  • DOI: 10.2147/ndt.s222966
  • NAID: 120007132754
  • Peer Reviewed / Open Access
• [Journal Article] Neuroimaging of Alzheimer's disease: focus on amyloid and tau PET. (2019)
  • Author(s): Matsuda H, Shigemoto Y, Sato N.
  • Journal Title: Jpn J Radiol Volume: 37 Issue: 11 Pages: 735-749
  • DOI: 10.1007/s11604-019-00867-7
  • NAID: 50014358257
  • Peer Reviewed
• [Journal Article] Association of deposition of tau and amyloid-β proteins with structural connectivity changes in cognitively normal older adults and Alzheimer’s disease spectrum patients. (2018)
  • Author(s): Shigemoto Y, Sone D, Maikusa N, Okamura N, Furumoto S, Kudo Y, Ogawa M, Takanno H, Yokoi Y, Sakata M, Tsukamoto T, Kato K, Sato N, Matsuda H
  • Journal Title: Brain Behav Volume: 8 Issue: 12
  • DOI: 10.1002/brb3.1145
  • Peer Reviewed / Open Access
• [Journal Article] Dissociation of tau deposits and brain atrophy in early Alzheimer’s disease: A combined positron emission tomography/magnetic resonance imaging study (2018)
  • Author(s): Shigemoto Y, Sone D, Imabayashi E, Maikusa N, Okamura N, Furumoto S, Kudo Y, Ogawa M, Takano H, Yokoi Y, Sakata M, Tsukamoto T, Kato K, Sato N, Matsuda H.
  • Journal Title: Front in Aging Neurosci Volume: 10 Pages: 223-223
  • DOI: 10.3389/fnagi.2018.00223
  • Peer Reviewed / Open Access
• [Presentation] アルツハイマー病の画像診断 (2021)
  • Author(s): 松田博史
  • Organizer: 第50回日本神経放射線学会
  • Invited
• [Presentation] 構造 MRI による認知症のコンピュータ診断 (2020)
  • Author(s): 松田博史
  • Organizer: 第29回脳ドック学会総会
  • Invited
• [Presentation] Association between subjfield volumes of the medial temporal lobe and neuropsychological assessments. (2019)
  • Author(s): Ogawa M, Sone D, Matsuda H
  • Organizer: Alzheimer’s Association International Conference
  • Int'l Joint Research
• [Presentation] Age-realted effects and sex differences in healthy controls for structural brain networks (2019)
  • Author(s): Saito Y, Okita K, Takano H, Shigemoto Y, Sato N, Matsuda H.
  • Organizer: Alzheimer’s Association International Conference
  • Int'l Joint Research
• [Presentation] Neuroimaging studies for mild Alzheimer’s disease (2019)
  • Author(s): Matsuda H
  • Organizer: "Conference Program of 3rd Asia-Pacific Aging Protection (APAP)"
  • Int'l Joint Research / Invited
• [Presentation] Amyloid and tau PET in dementia (2019)
  • Author(s): Matsuda H
  • Organizer: the 21st Zeelandia Symposium on Behavioral Neuroscience
  • Int'l Joint Research / Invited
• [Presentation] Amyloid and tau PET in Alzheimer’s disease (2019)
  • Author(s): Matsuda H
  • Organizer: International Conference on Ultra-high sensitity PET and Neuroimaging
  • Int'l Joint Research / Invited
• [Presentation] Association of tau and amyloid-βprotein to structural connectivity changes in cognitively healthy elderly and early Alzheimer’s disease (2018)
  • Author(s): Shigemoto Y Ogawa M Takano H, Sato N, Matsuda H.
  • Organizer: Alzheimer’s Association International Conference
  • Int'l Joint Research
• [Presentation] Influence of tau and amyloid burdenon brain connectivity (2018)
  • Author(s): Hiroshi Matsuda
  • Organizer: 中国核学会核医学分会年会
  • Invited