NilvadipineとPPARγアゴニストの併用により認知機能や脳血流量が改善した早期アルツハイマー病の1例
症例は76歳の男性で，高血圧と糖尿病を合併した早期アルツハイマー病(AD）である．前医で投薬されていた降圧薬(Ca拮抗薬のnifedipineとβ遮断薬のbetaxolol）をCa拮抗薬のnilvadipineとアンギオテンシンII受容体拮抗薬であるtelmisartanに変更し，さらにインスリン抵抗性改善薬のpioglitazoneを併用した．約6カ月後には，verbal fluency(1分間の動物名や野菜名の想起）やfrontal assessment batteryで改善がみられ，脳血流SPECTでも前頭葉や側頭頭頂葉で血流の改善が認められた．本症例は，脳移行性の高いnilvadipi...
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| Published in | 日本老年医学会雑誌 Vol. 45; no. 4; pp. 428 - 433 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本老年医学会
2008
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0300-9173 |
| DOI | 10.3143/geriatrics.45.428 |
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| Abstract | 症例は76歳の男性で，高血圧と糖尿病を合併した早期アルツハイマー病(AD）である．前医で投薬されていた降圧薬(Ca拮抗薬のnifedipineとβ遮断薬のbetaxolol）をCa拮抗薬のnilvadipineとアンギオテンシンII受容体拮抗薬であるtelmisartanに変更し，さらにインスリン抵抗性改善薬のpioglitazoneを併用した．約6カ月後には，verbal fluency(1分間の動物名や野菜名の想起）やfrontal assessment batteryで改善がみられ，脳血流SPECTでも前頭葉や側頭頭頂葉で血流の改善が認められた．本症例は，脳移行性の高いnilvadipineとペルオキシソーム増殖因子活性化受容体(PPAR）γ作用を有するpioglitazoneやtelmisartanの併用が認知機能や脳血流の改善に有効であったと考えられ，これら治療薬のADに対する効果について考察を加えた． |
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| AbstractList | 症例は76歳の男性で，高血圧と糖尿病を合併した早期アルツハイマー病(AD）である．前医で投薬されていた降圧薬(Ca拮抗薬のnifedipineとβ遮断薬のbetaxolol）をCa拮抗薬のnilvadipineとアンギオテンシンII受容体拮抗薬であるtelmisartanに変更し，さらにインスリン抵抗性改善薬のpioglitazoneを併用した．約6カ月後には，verbal fluency(1分間の動物名や野菜名の想起）やfrontal assessment batteryで改善がみられ，脳血流SPECTでも前頭葉や側頭頭頂葉で血流の改善が認められた．本症例は，脳移行性の高いnilvadipineとペルオキシソーム増殖因子活性化受容体(PPAR）γ作用を有するpioglitazoneやtelmisartanの併用が認知機能や脳血流の改善に有効であったと考えられ，これら治療薬のADに対する効果について考察を加えた． |
| Author | 高崎, 朗 岩本, 俊彦 羽生, 春夫 赤井, 知高 櫻井, 博文 佐藤, 友彦 |
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| References | 5) Hanyu H, Sakurai H, Hirao K, Sato T, Iwamoto T: Difference in practice effects depending on cerebral perfusion pattern in mild cognitive impairment. Int J Geriatr Psychiatry 2008; 23: 111-112. 11) Iwasaki K, Egashira N, Takagaki Y, Yoshimitsu Y, Hatip-Al-Khatib I, Mishima K, et al.: Nilvadipine prevents the impairment of spatial memory induced by cerebral ischemia combined with β-amyloid in rats. Biol Pharm Bull 2007; 30: 698-701. 16) Sastre M, Dewachter I, Rossner S, Bogdanovic N, Rosen E, Borghgraef P, et al.: Nonsteroidal anti-inflammatory drugs repress beta-secretase gene promotor activity by the activation pf PPARgamma. PNAS 2006; 103: 443-448. 18) Pedersen WA, McMillan PJ, Kulstad JJ, Leverenz JB, Craft S, Haynatzki GR: Rosiglitazone attenuates leraning and memory deficits in Tg2576 Alzheimer mice. Exp Neurol 2006; 199: 265-273. 17) Heneka MT, Sastre K, Dumitrescu-Ozimek L, Hanke A, Dewachter I, Kuiperi C, et al.: Acute treatment with PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. Brain 2005; 128: 1442-1453. 21) Watson GS, Cholerton BA, Reger MA, Baker LD, Plymate SR, Asthana S, et al.: Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone. A preliminary study. Am J Geriatr Psychiatry 2005; 13: 950-958. 1) 羽生春夫: 認知症治療を再考する. 生活習慣病の観点で認知症治療を再考する. 老年精神医学 2008; 19: 93-99. 22) 松沢俊興, 櫻井 孝, 明 太一, 芳野 弘, 高田俊宏, 横野浩一: ピオグリタゾンにより認知機能の改善が認められたアルツハイマー病を合併した高齢者糖尿病の1例. 糖尿病 2007; 50: 819-823. 2) Hirata Y, Matsuda H, Nemoto K, Ohnishi T, Hirao K, Yamashita F, et al.: Voxel-based morphometry to discriminate early Alzheimer's disease from controls. Neurosci Lett 2005; 382: 269-274. 6) Monsch AU, Bondi MW, Butters N, Salmon DP, Katzman R, Thal LJ: Comparisons of verbal fluency tasks in the detection of dementia of the Alzheimer type. Arch Neurol 1992; 49: 1253-1258. 12) Hanyu H, Hirao K, Shimizu S, Iwamoto T, Koizumi K, Abe K: Favourable effects of nilvadipine on cognitive function and regional cerebral blood flow on SPECT in hypertensive patients with mild cognitive impairment. Nucl Med Commun 2007; 28: 281-287. 13) Hanyu H, Hirao K, Shimizu S, Sato T, Kiuchi A, Iwamoto T: Nilvadipine prevents cognitive decline of patients with mild cognitive impairment. Int J Geriatr Psychiatry 2007; 22: 1264-1266. 20) Inestrosa NC, Godoy JA, Quintanilla RA, Koenig CS, Bronfman M: Peroxisome proliferator-acrivated receptor γ is expressed in hippocampal neurons and its activation prevents β-amyloid neurodegeneration: role of Wnt signaling. Exp Cell Res 2005; 304: 91-104. 3) Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE: A diagnostic approach in Alzheimer's disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med 1995; 36: 1238-1248. 10) Paris D, Quadros A, Humphrey J, Patel N, Crescentini R, Crawford F, et al.: Nilvadipine antagonizes both Aβ vasoactivity in isolated arteries, and the reduced cerebral blood flow in APPsw transgenic mice. Brain Res 2004; 999: 53-61. 9) Ohtsuka M, Ono T, Hiroi J, Esumi K, Kikuchi H, Kumada S: Comparison of the cardiovascular effect of FR342235, a new dihydropyridine, with other calcium antagonists. J Cardiovasc Pharmacol 1983; 5: 1074-1082. 8) Forette F, Seux M-L, Staessen JA, Thijs L, Babarskiene M-R, Babeanu S, et al.: The prevention of dementia with antihypertensive treatment. New evidence from the systolic hypertension in Europe (Syst-Eur) study. Arch Intern Med 2002; 162: 2046-2052. 4) Mizumura S, Kumita S, Cho K, Ishihara M, Nakajo H, Toba M, et al.: Development of quantitative analysis method for stereotactic brain image: Assessment of reduced accumulation in extent and severity using anatomical segmentation. Ann Nucl Med 2003; 17: 289-295. 14) Ohrui T, Tomita N, Sato-Nakagawa T, Matsui T, Maruyama M, Niwa K, et al.: Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression. Neurology 2004; 63: 1324-1325. 7) Jones S, Laukka EJ, Backman L: Differential verbal fluency deficits in the preclinical stages of Alzheimer's disease and vascular dementia. Cortex 2006; 42: 347-355. 19) Camacho IE, Serneels L, Spittaels K, Merchiers P, Dominguez D, De Strooper B: Peroxisome-proliferator-activated receptor gamma induces a clearance mechanism for the amyloid-beta peptide. J Neurosci 2004; 24: 10908-10917. 15) Benson SC, Pershadsingh HA, Ho CI, Chittiboyina A, Desai P, Pravenec M, et al.: Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPRAγ-modulating activity. Hypertension 2004; 43: 993-1002. |
| References_xml | – reference: 5) Hanyu H, Sakurai H, Hirao K, Sato T, Iwamoto T: Difference in practice effects depending on cerebral perfusion pattern in mild cognitive impairment. Int J Geriatr Psychiatry 2008; 23: 111-112. – reference: 16) Sastre M, Dewachter I, Rossner S, Bogdanovic N, Rosen E, Borghgraef P, et al.: Nonsteroidal anti-inflammatory drugs repress beta-secretase gene promotor activity by the activation pf PPARgamma. PNAS 2006; 103: 443-448. – reference: 22) 松沢俊興, 櫻井 孝, 明 太一, 芳野 弘, 高田俊宏, 横野浩一: ピオグリタゾンにより認知機能の改善が認められたアルツハイマー病を合併した高齢者糖尿病の1例. 糖尿病 2007; 50: 819-823. – reference: 9) Ohtsuka M, Ono T, Hiroi J, Esumi K, Kikuchi H, Kumada S: Comparison of the cardiovascular effect of FR342235, a new dihydropyridine, with other calcium antagonists. J Cardiovasc Pharmacol 1983; 5: 1074-1082. – reference: 19) Camacho IE, Serneels L, Spittaels K, Merchiers P, Dominguez D, De Strooper B: Peroxisome-proliferator-activated receptor gamma induces a clearance mechanism for the amyloid-beta peptide. J Neurosci 2004; 24: 10908-10917. – reference: 10) Paris D, Quadros A, Humphrey J, Patel N, Crescentini R, Crawford F, et al.: Nilvadipine antagonizes both Aβ vasoactivity in isolated arteries, and the reduced cerebral blood flow in APPsw transgenic mice. Brain Res 2004; 999: 53-61. – reference: 12) Hanyu H, Hirao K, Shimizu S, Iwamoto T, Koizumi K, Abe K: Favourable effects of nilvadipine on cognitive function and regional cerebral blood flow on SPECT in hypertensive patients with mild cognitive impairment. Nucl Med Commun 2007; 28: 281-287. – reference: 18) Pedersen WA, McMillan PJ, Kulstad JJ, Leverenz JB, Craft S, Haynatzki GR: Rosiglitazone attenuates leraning and memory deficits in Tg2576 Alzheimer mice. Exp Neurol 2006; 199: 265-273. – reference: 17) Heneka MT, Sastre K, Dumitrescu-Ozimek L, Hanke A, Dewachter I, Kuiperi C, et al.: Acute treatment with PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. Brain 2005; 128: 1442-1453. – reference: 13) Hanyu H, Hirao K, Shimizu S, Sato T, Kiuchi A, Iwamoto T: Nilvadipine prevents cognitive decline of patients with mild cognitive impairment. Int J Geriatr Psychiatry 2007; 22: 1264-1266. – reference: 15) Benson SC, Pershadsingh HA, Ho CI, Chittiboyina A, Desai P, Pravenec M, et al.: Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPRAγ-modulating activity. Hypertension 2004; 43: 993-1002. – reference: 1) 羽生春夫: 認知症治療を再考する. 生活習慣病の観点で認知症治療を再考する. 老年精神医学 2008; 19: 93-99. – reference: 6) Monsch AU, Bondi MW, Butters N, Salmon DP, Katzman R, Thal LJ: Comparisons of verbal fluency tasks in the detection of dementia of the Alzheimer type. Arch Neurol 1992; 49: 1253-1258. – reference: 8) Forette F, Seux M-L, Staessen JA, Thijs L, Babarskiene M-R, Babeanu S, et al.: The prevention of dementia with antihypertensive treatment. New evidence from the systolic hypertension in Europe (Syst-Eur) study. Arch Intern Med 2002; 162: 2046-2052. – reference: 21) Watson GS, Cholerton BA, Reger MA, Baker LD, Plymate SR, Asthana S, et al.: Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone. A preliminary study. Am J Geriatr Psychiatry 2005; 13: 950-958. – reference: 7) Jones S, Laukka EJ, Backman L: Differential verbal fluency deficits in the preclinical stages of Alzheimer's disease and vascular dementia. Cortex 2006; 42: 347-355. – reference: 20) Inestrosa NC, Godoy JA, Quintanilla RA, Koenig CS, Bronfman M: Peroxisome proliferator-acrivated receptor γ is expressed in hippocampal neurons and its activation prevents β-amyloid neurodegeneration: role of Wnt signaling. Exp Cell Res 2005; 304: 91-104. – reference: 4) Mizumura S, Kumita S, Cho K, Ishihara M, Nakajo H, Toba M, et al.: Development of quantitative analysis method for stereotactic brain image: Assessment of reduced accumulation in extent and severity using anatomical segmentation. Ann Nucl Med 2003; 17: 289-295. – reference: 2) Hirata Y, Matsuda H, Nemoto K, Ohnishi T, Hirao K, Yamashita F, et al.: Voxel-based morphometry to discriminate early Alzheimer's disease from controls. Neurosci Lett 2005; 382: 269-274. – reference: 3) Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE: A diagnostic approach in Alzheimer's disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med 1995; 36: 1238-1248. – reference: 11) Iwasaki K, Egashira N, Takagaki Y, Yoshimitsu Y, Hatip-Al-Khatib I, Mishima K, et al.: Nilvadipine prevents the impairment of spatial memory induced by cerebral ischemia combined with β-amyloid in rats. Biol Pharm Bull 2007; 30: 698-701. – reference: 14) Ohrui T, Tomita N, Sato-Nakagawa T, Matsui T, Maruyama M, Niwa K, et al.: Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression. Neurology 2004; 63: 1324-1325. |
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| SubjectTerms | Nilvadipine PPARγアゴニスト アルツハイマー病 糖尿病 高血圧 |
| Title | NilvadipineとPPARγアゴニストの併用により認知機能や脳血流量が改善した早期アルツハイマー病の1例 |
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