Goekoop R, Duschek E J J, Knol D L, Barkhof F, Netelenbos C, Scheltens Ph, Rombouts S A R B
Department of Neurology, VU University Medical Center, De Boelelaan 1117 1081 HV, Amsterdam, The Netherlands.
Neuroimage. 2005 Mar;25(1):63-75. doi: 10.1016/j.neuroimage.2004.11.012. Epub 2005 Jan 12.
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 gyrus, 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.
雷洛昔芬是一种仅用于女性的选择性雌激素受体调节剂（SERM），但其在男性受试者中的应用也越来越受到关注。随着越来越多的患者可能从雷洛昔芬中获益，评估其对脑功能影响的需求也日益增加。雌激素对脑功能的影响非常微妙，难以通过神经心理学评估检测出来。然而，功能成像技术在检测此类变化方面相对较为成功。本研究使用功能磁共振成像（fMRI）来检查雷洛昔芬治疗对记忆功能的影响。在健康老年男性（n = 28；平均年龄63.6岁，标准差2.4）进行面部编码范式任务时进行扫描。在基线时以及用雷洛昔芬（n = 14）或安慰剂（n = 14）治疗3个月后进行扫描。使用混合效应统计分析（FSL）分析治疗效果。任务执行期间的激活涉及双侧顶叶和前额叶区域、前扣带回以及双侧额下回、枕叶和颞中区域。与安慰剂相比，雷洛昔芬治疗显著增强了这些结构中的激活（Z > 3.1），颞中区域除外。安慰剂组的任务执行准确性降低（P = 0.02），而雷洛昔芬组保持不变（P = 0.60）。总之，雷洛昔芬治疗增强了多个不同认知领域区域的脑激活，表明对皮质觉醒有影响。这种影响可能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、语言技能和情景记忆的影响。需要进一步的神经心理学评估来检验这些预测的有效性。
