Effects of Testosterone on Brain Function on Elderly Men

本提案是根据NIA PAR 03-056提交的。该报告是在“提高老年人生活质量”的主题下提交的，准则11，干预研究。在男性中，睾酮（T）水平从30岁到80岁下降约50%，大多数70岁以上的男性可以被归类为性腺功能减退。这种T随年龄增长而逐渐丧失的现象，通常被称为“男性更年期”，可能会产生重大的认知后果。事实上，在疑似男性更年期的男性中，记忆力丧失是第三大最常见的症状。流行病学和干预研究都强调了T在维持认知功能方面的重要性。尽管与T损失相关的高发病率，但很少有研究专门调查T对老年男性的神经认知影响。这项研究计划的长期目标是调查类固醇激素对认知和大脑的影响。 衰老为此，具体的目标是研究T对性腺功能减退男性的空间记忆和功能性脑激活的影响。16名男性将参加一项随机、安慰剂对照、T干预研究。主要的结果指标将是空间导航虚拟现实测试和认知功能标准化测试的行为表现。此外，为了评估T动作的神经基础，将在虚拟现实空间记忆任务期间通过功能性MRI评估大脑激活。我们的中心假设是，T替代将证明有利于老年男性的神经认知功能。具体来说，我们假设T补充将增加激活海马和海马旁系统支持人类空间记忆。该提案在其方法上是独特的，因为它采用了虚拟现实导航任务来评估性腺功能减退男性的认知和大脑功能。这个任务作为一个很好的神经认知探针，以评估的假设，因为它elevenness大脑激活和年龄相关的变化，在这些特定的神经系统，是明显敏感的T行动。这项研究的重要性在于，它不仅为我们提供了T调节的认知系统的详细说明，而且还为我们提供了对这些相同效应的假定神经解释。最终这 在制定干预战略以预防或改善高危老年人的认知能力下降方面，这项工作将被证明是至关重要的。

This proposal is being submitted in response to NIA PAR 03-056. It is being submitted under the topic "Improve Quality of Life of Older People," guideline 11, Intervention Studies. In men, testosterone (T) levels decline by approximately 50% from ages 30 to 80 and a majority of men over age 70 can be classified as hypogonadal. This progressive loss of T with age in men, often called the "andropause", may have significant cognitive consequences. Indeed, among men with suspected andropause, memory loss is the third most commonly reported symptom. Both epidemiologic and intervention studies highlight the importance of T in maintaining cognitive function. Despite the high morbidity associated with T loss, there have been few studies specifically investigating the neurocognitive effects of T in elderly men. The long term goal of this program of research is to investigate the effects of steroid hormones on cognitive and brain aging. To that end, the specific objective is to investigate the effects of T on spatial memory and functional brain activation in hypogonadal men. Sixteen men will participate in a randomized, placebo-controlled, T intervention study. The principal outcome measures will be behavioral performance on virtual reality tests of spatial navigation and standardized tests of cognitive function. In addition, to assess the neural basis of T action, brain activation will be assessed by functional MRI during a virtual reality spatial memory task. Our central hypothesis is that T replacement will prove beneficial for neurocognitive function in elderly men. Specifically, we hypothesize that T supplementation will increase activation in the hippocampal and parahippocampal system supporting human spatial memory. This proposal is unique in its approach in that it adopts a virtual reality navigation task to assess cognitive and brain function in hypogonadal men. This task serves as an excellent neurocognitive probe to evaluate the hypotheses as it elicits brain activation and age-related changes in those specific neural systems that are demonstrably sensitive to T action. The proposed research is significant in that it will provide us with a detailed account not only of the cognitive systems modulated by T, but also provide us with a putative neural explanation of those same effects. Ultimately, this work will prove essential in the development of intervention strategies to prevent or ameliorate cognitive decline among at-risk elderly individuals.