Effects of Testosterone on Brain Function on Elderly Men

睾酮对老年男性脑功能的影响

• 批准号: 6920700
• 负责人: SCOTT D. MOFFAT
• 金额: $ 6.8万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-15 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6920700
• 关键词: aging; clinical research; cognition; functional magnetic resonance imaging; hippocampus; hormone regulation /control mechanism; hormone therapy; human old age (65+); human subject; human therapy evaluation; male; memory; patient oriented research; performance; testosterone

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.

该提案是为了响应 NIA PAR 03-056 而提交的。它是在“改善老年人的生活质量”主题下提交的，准则 11，干预研究。在男性中，从 30 岁到 80 岁，睾酮 (T) 水平下降约 50%，大多数 70 岁以上的男性可归类为性腺功能减退症。男性随着年龄的增长 T 逐渐丧失，通常被称为“男性更年期”，可能会产生严重的认知后果。事实上，在疑似男性更年期的男性中，记忆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 在维持认知功能中的重要性。尽管与 T 丢失相关的发病率很高，但很少有研究专门调查 T 对老年男性的神经认知影响。该研究计划的长期目标是研究类固醇激素对认知和大脑的影响 老化。为此，具体目标是研究 T 对性腺功能减退男性空间记忆和功能性大脑激活的影响。十六名男性将参加一项随机、安慰剂对照、T 干预研究。主要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 替代将被证明对老年男性的神经认知功能有益。具体来说，我们假设补充 T 会增加支持人类空间记忆的海马和海马旁系统的激活。该提案的独特之处在于它采用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。这项任务可以作为评估假设的优秀神经认知探针，因为它会引发大脑激活以及那些对 T 作用明显敏感的特定神经系统中与年龄相关的变化。这项研究的意义重大，因为它不仅为我们提供了由 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 事实证明，制定干预策略以预防或改善高危老年人认知能力下降的工作至关重要。