The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer's disease.
The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer's disease.
复制标题
乙酰胆碱释放剂利诺吡啶可增加阿尔茨海默病患者的顶叶区域脑血流量。
DOI：
10.1007/s002130050339
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发表时间：
1997
影响因子：
3.4
通讯作者：
Hoffer,PB
中科院分区：
文献类型：
--
作者：
vanDyck,CH;Lin,CH;Robinson,R;Cellar,J;Smith,EO;Nelson,JC;Arnsten,AF;Hoffer,PB
据报道，通过单光子发射计算机断层扫描 (SPECT) 测量受阿尔茨海默病 (AD) 影响的大脑区域，中枢作用的胆碱能药物可以增加局部脑血流量 (rCBF)。我们研究了乙酰胆碱释放剂利诺吡啶 (LPD) 对疑似 AD 患者 SPECT rCBF 的影响。 24 名 AD 患者（12 男，12 华氏度；平均年龄±SD = 68.9±8.2 岁）和 13 名健康对照者（8 男，5 华氏度；68.4±8.0 岁）参与研究。在双盲试验中，AD 患者在基线时使用 20 mCi 的 Tc-99m-ECD 进行扫描，并在接受 LPD 40 mg TID (n= 15) 或安慰剂 TID (n= 9) 治疗 4 周后进行扫描。对健康受试者进行扫描，以与基线 AD 扫描进行比较。皮质/小脑 rCBF 比率是针对九个皮质结构得出的。与对照组相比，患者的顶叶联合皮质减少了 20.6%。使用 LPD 治疗的患者显示顶叶 rCBF 增加了 4.1±5.8%；而安慰剂治疗组则下降了-2.0±7.4% (F= 5.13;df= 1, 22;P= 0.03)。这些数据支持这样的结论：AD 中的 rCBF 异常在某种程度上确实是“功能性的”，并且可以通过药物干预选择性地改变。 LPD 和其他胆碱能 AD 药物治疗中观察到的顶叶激活表明在评估这些药物的过程中测量顶叶神经心理功能的重要性。
Centrally acting cholinergic drugs have been reported to increase regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) in brain regions affected by Alzheimer’s disease (AD). We studied the effects of the acetylcholine releaser linopirdine (LPD) on SPECT rCBF in patients with probable AD. Twenty-four AD patients (12 M, 12 F; mean age ± SD = 68.9 ±8.2 years) and 13 healthy controls (8 M, 5 F; 68.4 ± 8.0 years) participated. AD patients were scanned with 20 mCi of Tc-99m-ECD at baseline and following 4 weeks of treatment with LPD 40 mg TID (n= 15) or placebo TID (n= 9) in a double-blind trial. Healthy subjects were scanned for comparison with baseline AD scans. Cortical/cerebellar rCBF ratios were derived for nine cortical structures. The combined parietal association cortex showed a 20.6% reduction in patients relative to controls. Patients treated with LPD showed an increase in parietal rCBF of 4.1 ± 5.8%; whereas those treated with placebo showed a decrease of −2.0 ± 7.4% (F= 5.13;df= 1, 22;P= 0.03). These data support the conclusion that rCBF abnormalities in AD are, in part, truly “functional” and can be selectively altered with pharmacological interventions. The parietal activation seen with LPD and other cholinergic AD drug therapies suggests the importance of measuring parietal lobe neuropsychological function in the course of evaluating these drugs.