Hormone and Neurotransmitter Interactions in Cognitive Aging

此应用程序是一个NIH K 01指导研究科学家发展奖，我将获得 必要的专业知识，以建立自己作为一个独立的研究者探索神经生物学 潜在的认知老化我将接受一种特定方法的培训，以研究神经生物学 认知老化的基础与精神药理学操作的联合使用， 认知和功能性磁共振成像（fMRI）从两个既定的专家在这些领域， Paul纽豪斯，医学博士安德鲁·赛金心理学博士在纽豪斯和赛金博士的指导下，我 将参加现场驻留，教程，课程和动手研究项目。本次培训将 为我提供了独特的专业知识，因为我联合收割机结合了我在认知心理学方面的先前训练， 利用精神药理学操作和功能磁共振成像的尖端组合来研究 认知老化的神经生物学 作为我训练的一个组成部分，我将进行两项药理学功能磁共振成像研究， 研究结果显示胆碱能完整性在观察雌激素对认知的影响中的重要性。研究1 将测试这一假设，即当老年妇女激活更多的额叶时， 相对于枕叶皮质的神经元功能受胆碱能完整性和雌激素治疗的调节。研究2将测试 假设胆碱能系统的老化主要是负责与年龄相关的神经 注意力、工作记忆和情景记忆任务中的补偿。研究2还将使用 雌激素调节胆碱能相关的认知过程。这些研究将是首次将联合收割机 强有力的胆碱能药物挑战，性激素治疗和功能磁共振成像， 检查神经递质-激素相互作用对认知的影响。这些研究的结果将 为胆碱能完整性和雌激素治疗对大脑和认知功能的重要性提供证据 在老年女性中发挥作用。了解雌激素对认知影响的神经生物学基础是 这对未来开发年龄相关认知功能障碍的治疗策略很重要。 相关性（参见说明）： 这些研究将强调认知老化背后的神经生物学知识的重要性， 临床干预的未来设计。结果也将是重要的理解为什么先前 雌激素对认知的影响试验失败了，因为老年妇女的胆碱能系统受损 这样就看不到雌激素的积极作用。

This application is for an NIH K01 Mentored Research Scientist Development Award where I will gain the xpertise necessary to establish myself as an independent investigator exploring the neurobiology underlying cognitive aging. I will receive training in a specific approach to investigating the neurobiological underpinnings of cognitive aging with the combined use of psychopharmacological manipulations of cognition and functional magnetic resonance imaging (fMRI) from two established experts in these fields, Paul Newhouse, M.D. and Andrew Saykin, Psy.D. Under the mentorship of Drs. Newhouse and Saykin, I will participate in on-site residencies, tutorials, courses, and hands-on research projects. This training will provide me with unique expertise as I combine my prior training in cognitive psychology with the ability to utilize the cutting edge combination of psychopharmacological manipulations and fMRI to study the neurobiology of cognitive aging. As an integral part of my training I will conduct two pharmacological fMRI studies that will extend my findings showing the importance of cholinergic integrity in observing effects of estrogen on cognition. Study 1 will test the hypothesis that neural compensation that is observed when older women activate more frontal relative to occipital cortex is modulated by cholinergic integrity and estrogen treatment. Study 2 will test the hypothesis that aging of the cholinergic system is principally responsible for age-associated neural compensation seen in attention, working memory, and episodic memory tasks. Study 2 will also use estrogen to modulate cholinergic-related cognitive processes. These studies will be the first to combine the powerful manipulations of cholinergic pharmacological challenge, sex hormone treatment, and fMRI to examine the neurotransmitter-hormone interaction effect on cognition. The results of these studies will provide evidence for the importance of cholinergic integrity and estrogen treatment on brain and cognitive functioning in older women. Understanding the neurobiology underlying the estrogen effect on cognition is important for the future development of treatment strategies for age-related cognitive dysfunction. RELEVANCE (See instructions): These studies will emphasize the importance of knowledge of the neurobiology underlying cognitive aging for the furure design of clinical interventions. The results will also be important for an understanding why prior trials of estrogen effects on cognition have failed because cholinergic systems in older women were impaired such that no positive effects of estrogen were seen.