アルツハイマー病に対する漢方薬の効果:認知機能、日常生活動作および脳血流への影響

2004 Fiscal Year Annual Research Report

• Project/Area Number: 16590554
• Research Institution: Tohoku University
• Principal Investigator: 荒井 啓行 東北大学, 大学院・医学系研究科, 教授 (30261613)
• Co-Investigator(Kenkyū-buntansha): 岩崎 鋼 東北大学, 大学院・医学系研究科, 助教授
• Keywords: アルツハイマー病 / 痴呆症 / 漢方薬 / 加味温胆湯 / 八味地黄丸 / 抑肝散 / 塩酸ドネペジル / 二重盲験ランダム化比較試験

Research Abstract

(1)アセチルコリン合成酵素(ChAr)をmRNAレベルで賦活する作用のある加味温胆湯(かみうんたんとう)がアルツハイマー病患者において認知機能の改善をもたらし、さらにこの効果はアルツハイマー病治療薬の第1選択薬である塩酸ドネペジルとの併用により一層高まることを明らかにした。併用によるコリン系の有害事象(下痢、吐き気、腹痛など)は見られなかった。脳血流シンチにおいては併用により前頭葉などで有意な血流改善効果が見られた。加味温胆湯はコルサコフ症候群モデルマウスにおいても同様のCbAT改善効果と学習機能の改善が見られた。
(2)広く腎虚の治療薬として使われる八味地黄丸は二重盲験ランダム化比較試験において平均年齢85歳、平均MMSE13.5ポイントの中等度から高度の血管障害を伴うアルツハイマー病患者の認知機能とADLを改善させた。有害事象は見られなかった。10名中8名で脳血流シンチにて脳血流増加が見られた。
(3)抑肝散は、肝の異常な陽気を抑え、易怒性や興奮に効果の知られている漢方であるが、痴呆症における問題行動や精神症状に対しては通常抗精神病薬が使用されるが、ADLを低下させる懸念があり、しばしば誤嚥性肺炎や転倒の原因となって来た。抑肝散が痴呆症における問題行動や精神症状に対してADLを低下させることなく改善する効果があることが示された。抑肝散使用中、誤嚥性肺炎や転倒は1例も見られなかった。

Research Products

• [Journal Article] The heterogeneity and natural history of mild cognitive impairment. (2005)
  • Author(s): Arai H, Maruyama M.
  • Journal Title: Arch.Neurol. 62 Pages: 163-164
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The neural correlates of driving performance identified using positron emission tomography. (2005)
  • Author(s): Horikawa E, Okamura N, Tashiro M, Sakurada Y, Maruyama M, AraiH, Yamaguchi K, Sasaki H, Yanai K, Itoh M
  • Journal Title: Brain and Cognition (In Press)
• [Journal Article] A Randomized Observer-Blind Controlled Trial of a Traditional Chinese Medicine, Yi-Gan San, on Behavioral and Psychological Symptoms and Activities of Daily Living in Dementia Patients. (2005)
  • Author(s): Iwasaki K, Satoh-Nakagawa T, Maruyama M, Monma Y, Nemoto M, Tomita N, Tanji H, Fujiwara H, Seki T, Fujii M, Arai H, Sasaki H.
  • Journal Title: J.Clin.Psychiatry 248-252 Pages: 248-252
• [Journal Article] Caregiver's burden and use of public services among dementia caregivers. (2005)
  • Author(s): Tanji H, Ootsuki M, Matsui T, Maruyama M, Nemoto M, Tomita N, Seki T, Iwasaki K, Arai H, Sasaki H.
  • Journal Title: Geriatr.Gerontol.Internat. (In Press)
• [Journal Article] Postural sway and falls in Alzheimer's disease : A prospective study. (2005)
  • Author(s): Horikawa E, Matsui T, Arai H, Seki T, Iwasaki K, Sasaki H.
  • Journal Title: Intern.Med. (In press)
• [Journal Article] Cognitive impairment and diffuse white matter atrophy inalcoholics (2005)
  • Author(s): Mochizuki H, Masaki T, Matsushita S, Ugawa Y, Kamakura K, Arai H, Motoyoshi K, Higuchi S.
  • Journal Title: Clin.Neurophys 116 Pages: 223-228
• [Journal Article] Brain-derived neurotrophic factor gene polymorphisms and Alzheimer's disease. (2005)
  • Author(s): Matsushita S, Arai H, et al.
  • Journal Title: J.Neural Transms (In press)
• [Journal Article] A randomized, double-blind, placebo-controlled clinical trial of the Chinese herbal medicine Ba Wei Di Huang Wan in the treatment of dementia. (2004)
  • Author(s): Iwasaki K, Kobayashi S, Chimura Y, Taguchi M, Inoue K, Akiba T, Arai H, Cyong J-C, Sasaki H.
  • Journal Title: J.Am.Geriatr.Soc. 52 Pages: 1518-1521
• [Journal Article] Styrylbenzoxazole derivatives for in vivo imaging of amyloid plaques in the brain. (2004)
  • Author(s): Okamura N, Suemoto T, Shimadzu H, Suzuki M, Shiomitsu T, Akatsu H, Yamamoto T, Staufenbiel M, Yanai K. Arai H, Sasaki H, Kudo Y, Sawada T.
  • Journal Title: J.Neuroscience 24 Pages: 2535-2541
• [Journal Article] A novel imaging probe for in vivo detection of neuritic and duffuse plaques in the brain. (2004)
  • Author(s): Okamura N, Suemoto T, Shiomitsu T, Suzuki M, Shimadzu H, Akatsu H, Yamamoto T, Arai H, Sasaki H. Yanai K, Staufenbiel M, Kudo Y, Sawada T.
  • Journal Title: J.Mol.Neurosci 24 Pages: 247-256
• [Journal Article] Cerebrospinal fluid tau protein and periventricular white matter lesions in aging, stable and progressive mild cognitive impairment : Implications for two major pathways. (2004)
  • Author(s): Maruyama M, Matsui T, Tanji H, Memoto M, Tomita N, Ootsuki M, Arai H, Sasaki H.
  • Journal Title: Arch.Neurol. 61 Pages: 716-720
• [Journal Article] Angiotensin converting enzyme inhibitors and incidence of Alzheimer's disease in Japan. (2004)
  • Author(s): Ohrui T, Matsui T, Yamaya M, Arai H, Ebihara S.Maruyama M, Sasaki H.
  • Journal Title: J.Am.Geriatr.Soc. 52 Pages: 649-650
• [Journal Article] Acupuncture for gait disorders in the elderly. (2004)
  • Author(s): Seki T, Kurusu M, Arai H, Sasaki H.
  • Journal Title: J.Am.Geriatr.Soc. 52 Pages: 643-644
• [Journal Article] Effects of the Chinese herbal medicine "Ba Wei Di Huang Wan" in the reatment of dementia : A SPECT cerebral blood flow examination and a randomized, double-blind, placebo-controlled clinical trial for cognitive function and A (2004)
  • Author(s): Iwasaki K, Kobayashi S, Chimura Y, Taguchi M, Inoue K, Akiba T, Arai H, Cyong J-C, Sasaki H.
  • Journal Title: Geriatr.Gerontol.Internat. 4 Pages: S124-S128
• [Journal Article] Mild cognitive impairment-beyond controversies towards consensus : report of the international working group on Mild cognitive impairment. (2004)
  • Author(s): Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund L-O, Nordberg A, Backman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, De Leon M, DeCarli C, Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack A, Jorm A, Richie K, Van Dubin C, Visser P, Petersen RC.
  • Journal Title: J.Intern.Med. 256 Pages: 240-246
• [Journal Article] Arg(184)His mutant GTP cyclohydrolase I, causing recessive hyperphenylalaninemia, is responsible for dopa-responsive dystonia with parkinsonism : A case report. (2004)
  • Author(s): Kikuchi A, Takeda A, Fujihara K, Kimpara T, Shiga Y, Tanji H, Nagai M, Ichinose H, Urano F, Okamura N, Arai H, Itoyama Y.
  • Journal Title: Movement Disorders 19 Pages: 590-593
• [Journal Article] Effect of Kami-Untan-To on the impairment of leaning nd memory induced by thiamine-deficient feeding in mice. (2004)
  • Author(s): Nakagawasai O, Yamadera F, Iwasaki K, Arai H, Taniguchi R, Tan-no K, Sasaki H, Tadano T.
  • Journal Title: Neuroscience 125 Pages: 233-241
• [Journal Article] Effects of brain-penetrating ACE inhibitors on Alzheimer's disease progression. (2004)
  • Author(s): Ohrui T, Tomita N, Satoh-Nakagawa T, Matsui T, Maruyama M, Niwa K, Arai H, Sasaki H.
  • Journal Title: Neurology 63 Pages: 1324-1325
• [Journal Article] Increased plasma 8-isoprostane levels in hypertensive subjects : the Tsurugaya project (2004)
  • Author(s): Hozawa A, Ebihara S, et al
  • Journal Title: Hypertension Research 27 Pages: 557-561
• [Patent(Industrial Property Rights)] 漢方薬によるアミロイド凝集抑制作用等に関する研究 (2004)
  • Inventor(s): 荒井啓行, 岩崎 鋼
  • Industrial Property Rights Holder: 荒井啓行, 岩崎 鋼
  • Industrial Property Number: 2004-378195
  • Filing Date: 2004-12-27