Division of Alzheimer Neurobiology, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
J Alzheimers Dis. 2011;24(1):109-23. doi: 10.3233/JAD-2010-101290.
The effects of galantamine (16 to 24 mg/day) treatment on brain functional activities (blood flow and glucose metabolism) were examined in 18 patients with mild Alzheimer's disease (AD) in relation to brain acetylcholinesterase (AChE) activity and nicotinic receptors and cognitive function. The study consisted of an initial double-blind phase of three months (short-term) followed by an open-label phase until twelve months after the beginning of the study (long-term). The AD patients underwent positron emission tomography (PET) studies with the tracers [15O]-H2O for measurement of regional cerebral blood flow (rCBF) at baseline, 3 weeks, 3 and 12 months treatment, and [18F]-fluoro-deoxyglucose (FDG) for measurement of regional cerebral metabolic rate for glucose (rCMRglc) at baseline and 12 months. A battery of neuropsychological assessments was performed on each patient in order to follow changes in cognition during the treatment period. Throughout the study, different cortical areas showed significant increases in rCBF after galantamine treatment. rCBF positively correlated with AChE activity, nicotinic receptors and cognition. In addition to these positive changes, an increase in rCMRglc in the frontal brain region and stabilization in other cortical areas was observed after 12 months galantamine treatment. This stabilization in rCMRglc was also correlated with a stabilization of cognition. Our results ultimately suggest that treatment with galantamine has a long-term positive effect on brain perfusion and rCMRglc and stabilizes cognition.
我们考察了 18 例轻度阿尔茨海默病（AD）患者在接受加兰他敏（16-24mg/天）治疗时大脑功能活动（血流和葡萄糖代谢）的变化，与大脑乙酰胆碱酯酶（AChE）活性、烟碱受体和认知功能有关。该研究包括三个月的初始双盲期（短期），随后进行开放标签期，直到研究开始后 12 个月（长期）。AD 患者接受正电子发射断层扫描（PET）研究，使用示踪剂[15O]-H2O 测量基线、3 周、3 个月和 12 个月治疗时的局部脑血流（rCBF），以及[18F]-氟代脱氧葡萄糖（FDG）测量基线和 12 个月时的局部脑葡萄糖代谢率（rCMRglc）。对每位患者进行了一系列神经心理学评估，以跟踪治疗期间认知的变化。在整个研究过程中，不同的皮质区在加兰他敏治疗后 rCBF 显著增加。rCBF 与 AChE 活性、烟碱受体和认知呈正相关。除了这些积极的变化，在接受加兰他敏治疗 12 个月后，额叶大脑区域的 rCMRglc 增加，其他皮质区域稳定。rCMRglc 的这种稳定也与认知的稳定相关。我们的研究结果最终表明，加兰他敏治疗对大脑灌注和 rCMRglc 有长期的积极影响，并稳定认知。
