Hormone and Neurotransmitter Interactions in Cognitive Aging

描述（由申请人提供）：本申请是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认知老化的神经生物学基础。我将接受培训，在一个特定的方法来调查认知老化的神经生物学基础与认知和功能性磁共振成像（fMRI）的心理药理学操作相结合的使用，从两个既定的专家在这些领域，保罗纽豪斯，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，我将参加现场实习、辅导、课程和动手研究项目。这次培训将为我提供独特的专业知识，因为我将联合收割机我以前在认知心理学方面的培训与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衰老的神经生物学的能力相结合。作为我培训的一个组成部分，我将进行两项药理学功能磁共振成像研究，这将扩展我的发现，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将测试的假设，观察到的神经补偿时，老年妇女激活更多的额叶相对于枕叶皮质胆碱能完整性和雌激素治疗调制。研究2将测试这一假设，即胆碱能系统的老化主要是负责与年龄相关的神经补偿注意，工作记忆和情景记忆任务。研究2还将使用雌激素来调节胆碱能相关的认知过程。这些研究将是第一个联合收割机结合胆碱能药物挑战，性激素治疗和功能磁共振成像的强大操作，以检查神经递质-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老年妇女大脑和认知功能的重要性提供证据。了解雌激素对认知影响的神经生物学基础对于未来开发年龄相关认知功能障碍的治疗策略非常重要。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对于临床干预措施的进一步设计的重要性。这些结果对于理解为什么以前的雌激素对认知影响的试验失败也很重要，因为老年妇女的胆碱能系统受损，因此没有看到雌激素的积极作用。

DESCRIPTION (provided by applicant): 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.