PET imaging of the in vivo brain acetylcholinesterase activity and nicotine binding in galantamine-treated patients with AD

被引:59
作者
Kadir, A.
Darreh-Shori, T.
Almkvist, O. [2 ,5 ]
Wall, A. [6 ]
Grut, M. [3 ]
Strandberg, B. [2 ]
Ringheim, A. [6 ]
Eriksson, B. [4 ]
Blomquist, G. [6 ,7 ]
Langstrom, B. [6 ]
Nordberg, A. [1 ,2 ]
机构
[1] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Neurobiol,Care Sci & Soc,Div Mol Neuropharma, S-14186 Huddinge, Sweden
[2] Karolinska Univ, Huddinge Hosp, Dept Geriatr Med, S-14186 Huddinge, Sweden
[3] Danderyd Hosp, Geriatr Clin, Stockholm, Sweden
[4] Janssen Cilag, Sollentuna, Sweden
[5] Univ Stockholm, Dept Psychol, S-10691 Stockholm, Sweden
[6] Uppsala PET Ctr Uppsala Imanet, Uppsala, Sweden
[7] Uppsala Univ, Dept Oncol Radiol & Clin Immunol, S-75105 Uppsala, Sweden
基金
英国医学研究理事会;
关键词
Alzheimer's disease; acetylcholinesterase; C-11-nicotine binding; positron emission tomography (PET); cerebrospinal fluid; plasma; cognitive function; attention; galantamine;
D O I
10.1016/j.neurobiolaging.2007.02.020
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
The effect of galantamine treatment on cortical acetylcholinesterase (AChE) activity and nicotinic receptor binding was investigated by positron emission tomography (PET) in 18 patients with mild Alzheimer's disease (AD) in relation to galantamine concentration and the patients' cognitive performances. The first 3 months of the study was of a randomized double-blind placebo-controlled design, during which 12 patients received galantamine (16-24 mg/day) and 6 patients the placebo, and this was followed by 9 months' galantamine treatment in all patients. The patients underwent PET examinations to measure cortical AChE activity (C-11-PMP) and C-11-nicotine binding. Neuropsychological tests were performed throughout the study. Inhibition (30-40%) of cortical AChE activity was observed after 3 weeks to 12 months of galantamine treatment. No significant change in mean cortical C-11-nicotine binding was observed during the study. C-11-Nicotine binding, however, positively correlated with plasma galantamine concentration. Both the changes of AChE activity and C-11-nicotine binding correlated positively with the results of a cognitive test of attention. In conclusion, galantamine caused sustained AChE inhibition for up to 12 months. At the individual level, the in vivo cortical AChE inhibition and C-11-nicotine binding were associated with changes in the attention domain of cognition rather than episodic memory. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:1204 / 1217
页数:14
相关论文
共 67 条
[1]   PSYCHOMETRIC DISCRIMINATION OF TETRAHYDROAMINOACRIDINE RESPONDERS IN ALZHEIMER PATIENTS [J].
ALHAINEN, K ;
HELKALA, EL ;
RIEKKINEN, P .
DEMENTIA, 1993, 4 (01) :54-58
[2]   Preserved cognitive function after 12 months of treatment with rivastigmine in mild Alzheimer's disease in comparison with untreated AD and MCI patients [J].
Almkvist, O ;
Darreh-Shori, T ;
Stefanova, E ;
Spiegel, R ;
Nordberg, A .
EUROPEAN JOURNAL OF NEUROLOGY, 2004, 11 (04) :253-261
[3]   Responder characteristics to a single oral dose of cholinesterase inhibitor:: A double-blind placebo-controlled study with tacrine in Alzheimer patients [J].
Almkvist, O ;
Jelic, V ;
Amberla, K ;
Hellström-Lindahl, E ;
Meurling, L ;
Nordberg, A .
DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 2001, 12 (01) :22-32
[4]  
ANDERSSON JLR, 1995, J NUCL MED, V36, P657
[5]  
[Anonymous], 2004, Neuropsychological Assessment
[6]  
BACKMAN L, 1994, J ABNORM PSYCHOL, V103, P361
[8]   Cognitive correlates of alterations in acetylcholinesterase in Alzheimer's disease [J].
Bohnen, NI ;
Kaufer, DI ;
Hendrickson, R ;
Ivanco, LS ;
Lopresti, B ;
Davis, JG ;
Constantine, G ;
Mathis, CA ;
Moore, RY ;
DeKosky, ST .
NEUROSCIENCE LETTERS, 2005, 380 (1-2) :127-132
[9]   Degree of inhibition of cortical acetylcholinesterase activity and cognitive effects by donepezil treatment in Alzheimer's disease [J].
Bohnen, NI ;
Kaufer, DI ;
Hendrickson, R ;
Ivanco, LS ;
Lopresti, BJ ;
Koeppe, RA ;
Meltzer, CC ;
Constantine, G ;
Davis, JG ;
Mathis, CA ;
DeKosky, ST ;
Moore, RY .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2005, 76 (03) :315-319
[10]  
Bores GM, 1996, J PHARMACOL EXP THER, V277, P728