Bohnen N I, Kaufer D I, Hendrickson R, Ivanco L S, Lopresti B J, Koeppe R A, Meltzer C C, Constantine G, Davis J G, Mathis C A, Dekosky S T, Moore R Y
University of Pittsburgh, Liliane S Kaufmann Building, Suite 811, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA.
J Neurol Neurosurg Psychiatry. 2005 Mar;76(3):315-9. doi: 10.1136/jnnp.2004.038729.
To determine in vivo cortical acetylcholinesterase (AChE) activity and cognitive effects in subjects with mild Alzheimer's disease (AD, n = 14) prior to and after 12 weeks of donepezil therapy.
Cognitive and N-[(11)C]methyl-piperidin-4-yl propionate ([(11)C]PMP) AChE positron emission tomography (PET) assessments before and after donepezil therapy.
Analysis of the PET data revealed mean (temporal, parietal, and frontal) cortical donepezil induced AChE inhibition of 19.1% (SD 9.4%) (t = -7.9; p<0.0001). Enzyme inhibition was most robust in the anterior cingulate cortex (24.2% (6.9%), t = -14.1; p<0.0001). Donepezil induced cortical inhibition of AChE activity correlated with changes in the Stroop Color Word interference scores (R(2) = 0.59, p<0.01), but not with primary memory test scores. Analysis of the Stroop test data indicated that subjects with AChE inhibition greater than the median value (>22.2%) had improved scores on the Stroop Color Word Test compared with subjects with less inhibition who had stable to worsening scores (t = -2.7; p<0.05).
Donepezil induced inhibition of cortical AChE enzyme activity is modest in patients with mild AD. The degree of cortical enzyme inhibition correlates with changes in executive and attentional functions.
确定轻度阿尔茨海默病（AD，n = 14）患者在多奈哌齐治疗12周前后的体内皮质乙酰胆碱酯酶（AChE）活性及认知效应。
在多奈哌齐治疗前后进行认知和N-[(11)C]甲基-哌啶-4-基丙酸酯（[(11)C]PMP）AChE正电子发射断层扫描（PET）评估。
PET数据分析显示，多奈哌齐诱导的平均（颞叶、顶叶和额叶）皮质AChE抑制率为19.1%（标准差9.4%）（t = -7.9；p<0.0001）。在前扣带回皮质中酶抑制作用最强（24.2%（6.9%），t = -14.1；p<0.0001）。多奈哌齐诱导的皮质AChE活性抑制与Stroop颜色词干扰分数的变化相关（R(2) = 0.59，p<0.01），但与初级记忆测试分数无关。Stroop测试数据分析表明，AChE抑制大于中位数（>22.2%）的受试者在Stroop颜色词测试中的分数有所改善，而抑制较少的受试者分数稳定或恶化（t = -2.7；p<0.05）。
在轻度AD患者中，多奈哌齐诱导的皮质AChE酶活性抑制作用较小。皮质酶抑制程度与执行和注意力功能的变化相关。
