Raloxifene exposure enhances brain activation during memory performance in healthy elderly males; its possible relevance to behavior
Raloxifene exposure enhances brain activation during memory performance in healthy elderly males; its possible relevance to behavior
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DOI：
10.1016/j.neuroimage.2004.11.012
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发表时间：
2005-03-01
期刊：
影响因子：
5.7
通讯作者：
Rombouts, SARB
中科院分区：
文献类型：
--
作者：
Goekoop, R;Duschek, EJJ;Rombouts, SARB
雷洛昔芬是一种选择性雌激素受体调节剂(SERM)，仅适用于女性，但越来越多的人考虑将其用于男性受试者。随着越来越多的患者可能受益于雷洛昔芬，评估其对大脑功能的影响的必要性越来越大。雌激素对大脑功能的影响是非常微妙的，很难通过神经心理学评估来检测。然而，功能成像技术在检测这种变化方面相对成功。本研究使用功能磁共振成像(FMRI)来检测雷洛昔芬治疗对记忆功能的影响。健康老年男性(n=28，平均年龄63.6岁，SD 2.4)在进行面部编码时进行扫描。扫描是在基线和雷洛昔芬(n=14)或安慰剂(n=14)治疗3个月后进行的。采用混合效应统计分析(FSL)进行疗效分析。任务执行过程中的激活涉及双侧顶叶和前额叶、扣带回前部，以及双侧前额叶、枕叶和内侧的下部。与安慰剂相比，雷洛昔芬治疗显著增强了这些结构的激活(Z>；3.1)，除了中颞区。任务执行准确性在安慰剂组降低(P=0.02)，但在雷洛昔芬组保持不变(P=0.60)。总而言之，雷洛昔芬治疗增强了跨越许多不同认知域的大脑区域的激活，这表明对大脑皮层唤醒有影响。这种影响可能会转化为对行为的微小影响，包括对注意力和工作记忆表现、执行功能、言语技能和情景记忆的影响。进一步的神经心理学评估是必要的，以检验这些预测的有效性。(C)2004 Elsevier Inc.保留所有权利。
Raloxifene is a selective estrogen receptor modulator (SERM) that is prescribed in females only, but its use in male subjects is increasingly considered. With a growing number of patients having potential benefit from raloxifene, the need for an assessment of its effects on brain function is growing. Effects of estrogens on brain function are very subtle and difficult to detect by neuropsychological assessment. Functional imaging techniques, however, have been relatively successful in detecting such changes. This study used functional magnetic resonance imaging (fMRI) to examine effects of raloxifene treatment on memory function. Healthy elderly males (n = 28; mean age 63.6 years, SD 2.4) were scanned during performance on a face encoding paradigm. Scans were made at baseline and after 3 months of treatment with either raloxifene (n = 14) or placebo (n = 14). Treatment effects were analyzed using mixed-effects statistical analysis (FSL). Activation during task performance involved bilateral parietal and prefrontal areas, anterior cingulate gyros, and inferior prefrontal, occipital, and mediotemporal areas bilaterally. When compared to placebo, raloxifene treatment significantly enhanced activation in these structures (Z > 3.1), except for mediotemporal areas. Task performance accuracy diminished in the placebo group (P = 0.02), but remained constant in the raloxifene group (P = 0.60). In conclusion, raloxifene treatment enhanced brain activation in areas spanning a number of different cognitive domains, suggesting an effect on cortical arousal. Such effects may translate into small effects on behavior, including effects on attention and working memory performance, executive functions, verbal skills, and episodic memory. Further neuropsychological assessment is necessary to test the validity of these predictions. (C) 2004 Elsevier Inc. All rights reserved.