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Clinical trials of anti-dementia drugs and biological markers

Research Project

Project/Area Number10680715
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

ARAI Hiroyuki  Tohoku University, Hospital Associate Prof, 医学部・附属病院, 助教授 (30261613)

Co-Investigator(Kenkyū-buntansha) 伊藤 正敏  東北大学, サイクロトロン・ラジオアイソトープセンター, 教授 (00125501)
Project Period (FY) 1998 – 1999
Project Status Completed(Fiscal Year 1999)
Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1999 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1998 : ¥1,300,000 (Direct Cost : ¥1,300,000)
KeywordsAlzheimer's disease / Herbal / Early diagnosis / CSF / tau protein / PET / タウ / 老年期痴呆 / tau蛋白
Research Abstract

A Japanese herbal medicine "Kami-Untan-To (KUT)" was first described in Japanese literature in 1626. KUT is composed of 13 different herbs, and has been used for a long time in the treatment of a variety of neuropsychiatric problems including depression and insomnia. Recently, Yabe et al. Have demonstrated that KUT increased both choline acetyltransferase (ChAT) and NGF at the protein and mRNA levels in cultured rat brain cells. Moreover, the same research group has reported that KUT improved mean latency on passive avoidance test in both basal forebrain lesioned and aged rats. KUT significantly improved the survival rate, and increased the number of ChAT-positive neurons in aged rats. Here, we report 12 months open clinical trials of KUT and a combination of estrogen, vitamin-E and NSAID to aim at slowing down the progression of AD. Twenty AD patients (MMSE score : 18.6【minus-plus】5.8) were receiving extracts from original KUT herbs, and 7 AD patients (MMSE score : 21.3【minus-plus】2.8) were placed on the combination therapy. Rate of cognitive decline as measured by group (1.4 point) and the combination group (1.5 point) as compared to 4.1 point in 32 control AD patient (MMSE score : 20.8【minus-plus】5.6) who received no medicines tested in the therapies for AD. Notably, CSF-ChAT levels were significantly (p=0.005, n=6) reduced following the KUT therapy. The efficacy of the KUT was most obvious at 3-month point. Our results suggest that traditional Japanese herbal medicines may serve a new intervention strategy for AD.

Report

(3results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report

Research Products

(62results)

All Other

All Publications

  • [Publications] Itabashi s.et al.: "Absence of association of al-antichymotrypsin polymorphisms with Alzheimer's disease : A report on autopsy-confirmed cases"Exp. Neurol.. 151. 237-240 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Arai H.et al.: "Cerebrospinal fluid tau protein as a potential diagnostic marker in Alzheimer's disease (Position Paper)"Neurobiol. Aging. 19. 125-126 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ronald et al.: "Molecular and biochemical markers of Alzheimer's disease"Neurobiol. Aging. 19. 109-116 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Higuchi S.et al.: "Mutation in the α-synuclein gene and sporadic Parkinson's disease, Alzheimer disease, and dementia with Lewy bodies in Japanese"Exp. Neurol.. 153. 164-166 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Higuchi S.et al.: "Regional cerebral glucose utilization is modlated by the dosage of Apolipoprotein E type 4 allele and al-antichymotrypsin type A allele in Alzheimer's disease"Alzheimer's Research. 4. 33-38 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Arai H.et al.: "No increase in cerebrospinal fluid tau protein levels in patients with vascular dementia"Neurosci. Lett.. 256. 174-176 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Urakami K.et al.: "A comparison of tau protein in cerebrospinal fluid between corticobasal degeneration and progressive supranuclear palsy"Neurosci. Lett.. 259. 127-129 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Higuchi M.et al.: "Apolipoprotein E and Alzheimer's disease : Therapeutic implications"CNS drugs.. 11. 411-420 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Morikawa Y.et al.: "Cerebrospinal fluid tau protein levels in demented and non-demented alcoholics"Alcohol. Clin. Exp. Res.. 23. 575-577 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakajoh K.et al.: "Relation between incidence of pneumonia and protective reflexes in post-stroke patients with oral and tube feeding"J. Intern. Med. In press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Isoe-Wada K.et al.: "Alternation in brain presenelin-1 mRNA expression in sporadic Alzheimer's disease"Eur. J. Neurol.. 6. 163-167 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishiguro K.et al.: "Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease"Neurosci. Lett.. 270. 91-94 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsui T.et al.: "A practical method to predict rate of cognitive decline in mild to moderate Alzheimer's disease"Neurology. 53. 2208-2209 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okamura N.et al.: "Cerebrospinal fluid levels of amyloid β-peptide but not tau have positive correlation with brain glucose metabolism in humans"Neurosci. Lett.. 273. 203-207 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Burger K.et al.: "CSF tau protein shows a better discrimination in young old (<70 years) than in old old patients with Alzheimer's disease compared with controls"Neurosci. Lett.. 277. 21-24 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Higuchi M.et al.: "Glucose hypometabolism and neuropathological correlates in brains of Dementia with Lewy bodies"Exp. Neurol .. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itabashi S. at al.: "Absence of association of α1-antichymotrypsin polymorphisms with Alzheimer's disease: A report on autopsy-confirmed cases."Exp. Neurol.. 151. 237-240 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Arai H. at al.: "Cerebrospinal fluid tau protein as a potential diagnostic marker in Alzheimer's disease (Position Paper)."Neurobiol. Aging.. 19. 125-126 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ronald et al.: "Molecular and biochemical markers of Alzheimer's disease."Neurobiol. Aging.. 19. 109-116 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Higuchi S. et al.: "Mutation in the α-synuclein gene and sporadic Parkinson's disease, Alzheimer's disease, and dementia with Lewy bodies in Japanese."Exp. Neurol.. 153. 164-166 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Higuchi M. et al.: "Regional cerebral glucose utilization is modlated by the dosage of Apolipoprotein E type 4 allele and al-antichymotrypsin type A allele in Alzheimer's disease."Alzheimer's Research.. 4. 33-38 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Arai H. et al.: "No increase in cerebrospinal fluid tau protein levels in patients with vascular dementia."Neurosci. Lett.. 256. 174-176 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Urakami K. et al.: "A comparison of tau protein in cerebrospinal fluid between corticobasal degeneration and progressive supranuclear palsy."Neurosci. Lett.. 259. 127-129 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Higuchi M. et al.: "Apolipoprotein E and Alzheimer's disease: Therapeutic implications."CNS drugs.. 11. 411-420 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Morikawa Y. et al.: "Cerebrospinal fluid tau protein levels in demented and non-demented alcoholics."Alcohol. Clin. Exp. Res.. 23. 575-577 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakajoh K. et al.: "Relation between incidence of pneumonia and protective reflexes in post-stroke patients with oral and tube feeding."J. Intern. Med.. In press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Isoe-Wada K. et al.: "Alternation in brain presenelin-1 mRNA expression in sporadic Alzheimer's disease."Eur. J. Neurol.. 6. 163-167

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Higuchi M. et al.: "Apolipoprotein E and Alzheimer's disease: Therapeutic implications."CNS drugs.. 11. 411-420 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Morikawa Y. et al.: "Cerebrospinal fluid tau protein levels in demented and non-demented alcoholics."Alcohol. Clin. Exp. Res.. 23. 575-577 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakajoh K. et al.: "Relation between incidence of pneumonia and protective reflexes in post-stroke patients with oral and tube feeding."J. Intern. Med.. In press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Isoe-Wada K. et al.: "Alternation in brain presenelin-1 mRNA expression in sporadic Alzheimer's diseases."Eur. J. Neurol.. 6. 163-167 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Isiguro K. et al.: "Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease."Neuroscri. Lett.. 270. 91-94 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsui T. et al.: "A practical method to predict rate of cognitive decline in mild to moderate Alzheimer's disease."Neurology.. 58. 2208-2209 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okamura N. et al.: "Cerebrospinal fluid levels of amyloid β-peptideィイD21-42ィエD2, but not tau have positive correlation with brain glucose metabolism in humans."Neuroscri. Lett.. 273. 203-207 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Burger K. et al.: "CSF tau protein shows a better discrimination in young old (<70 years) than in old old patients with Alzheimer's disease compared with controls."Neuroscri. Lett.. 277. 21-24 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Higuchi M. et al.: "Glucose hypometabolism and neuropathological correlated in brains of Dementia with Lewy bodies."Exp. Neurol.. In press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakajoh et al.: "Relation between incidence〜"J. Intern. Med.. (In press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Isoe Wada et al.: "Alternation in brain presenilin-1 mRNA〜"Exp. Neurol.. 6. 163-167 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakagawa et al.: "Silent cerebral infarction : a potential 〜"J. Intern. Med.. (In press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishiguro K. et al.: "Phosphorylated tau in human〜"Neuroscience Letters. 270. 91-94 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sekizawa et al.: "Amandatine and Pneumonia"Lancet. 353. 2157 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsui et al.: "A practical Method to predict〜"Neurology. 53. 2208-2209 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sasaki et al.: "Effects of air pollution and〜"Tohoku J. Exp. Med.. 186. 151-167 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Urakami et al.: "A comparison of tau protein"Neuroscience Letters. 259. 127-129 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakagawa et al.: "Amantadine and pneumonia"Lancet. 353. 1157 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Higuchi et al.: "Apolipoprotein E and Alzheimer's disease〜"CNS Drugs. 11. 411-420 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Morikawa et al.: "Cerebrospinal fluid tau protein〜"Alcohol. Clin. Exp. Res.. 23. 575-577 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakayama et al.: "Expression of human β-defensin〜"Ann. Neurol. 45. 685 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okamura et al.: "Cerebrospinal fluid levels of amyloid〜"Neuroscience Letters. 273. 203-207 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Burger et al.: "CSF tau protein shows a better〜"Neuroscience Letters. 277. 21-24 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakajoh et al.: "Longevity may decrease〜"J. Am. Geriat. Soc. 47. 1161-1162 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 荒井啓行: "老年期痴呆症と遺伝子多型"日本老年医学会雑誌. 36. 251-255 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 荒井啓行 ら: "高令者における肺炎の成立機序と〜"感染と抗菌薬. 2. 285-288 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 荒井啓行: "加味温胆湯"Medical Academy News. 720. (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kosaka.et al.: "Suruival of bed-ridden older patients" J.Am.Geriatr.Soc.46. 394 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Itabashi.et al.: "Absence of association of al-antichymotrypsin-." Exp. Neurol.151. 237-240 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishimura.et al.: "Basic and clinical studies on the measurement-." Methods Find Exp Clin Pharmacol. 20. 227-235 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Arai.et al.: "Cerebrospinal fluid tau protein as a-." Neurobiol. of Aging. 19. 125-126 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kanai.et al.: "Longitudinal study of cerebrospinal fluid." Ann. Neurol.44. 17-26 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Biguchi.et al.: "Mutation in the a-synuclein gene-." Exp. Neurol.153. 164-166 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Arai.et al.: "Proc. 4th WBO-CC Symposium." WBO-Collaborating Center for Well-beiry in Ag., 69-73 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Biguchi.et al.: "Quantitative functional braing-." Academic Press., 207-214 (1998)

    • Related Report
      1998 Annual Research Report

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Published : 1998-04-01   Modified : 2016-04-21  

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