Hormones and Cognition Over the Lifespan

一生中的激素和认知

• 批准号: 8149843
• 负责人: Miriam T. Weber
• 金额: $ 14.99万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8149843
• 关键词: Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Behavioral; Brain; Clinical; Clinical Trials; Cognition; Cognitive; Cognitive aging; Cognitive deficits; Dementia; Dendritic Spines; Development; Elderly; Endocrinology; Epidemiology; Estrogens; Event; Female; Foundations; Hormonal; Hormonal Change; Hormones; Hot flushes; Impaired cognition; Investigational Therapies; K-Series Research Career Programs; Knowledge; Lead; Life Cycle Stages; Longevity; Measurable; Measures; Mediating; Memory; Menopause; Mentored Patient-Oriented Research Career Development Award; Mentors; Methodology; Neuropsychology; Neurosciences; Outcome; Pattern; Performance; Perimenopause; Postpartum Period; Pregnancy; Pregnant Women; Research; Research Personnel; Research Proposals; Research Training; Risk; Risk Factors; Series; Sleep disturbances; Time; Training Programs; Woman; Work; axonal sprouting; cholinergic; critical period; depressive symptoms; experience; hypothalamic pituitary gonadal axis; improved; mild neurocognitive impairment; neuron loss; prevent; programs; protective effect; public health relevance; reproductive; reproductive hormone; statistics

DESCRIPTION (provided by applicant): Reproductive hormones have several protective effects on the brain, such as promoting cholinergic activity, reducing neuronal loss, and stimulating axonal sprouting and dendritic spine formation. In this application, it is hypothesized that reproductive events characterized by significant hormonal fluctuation (such as pregnancy and the menopausal transition) are associated with measurable decreases in cognition, and that multiple periods of estrogen depletion increases the risk of cognitive decline and dementia in later life. The overall aim of this Mentored Patient-Oriented Research Career Development Award (K23) is to lay the foundation for a programmatic approach to the study of hormones and cognition in women across the lifespan and to facilitate the candidate's development into an independent clinical neuroscience researcher. The candidate has extensive training and research experience in the neuropsychology of aging, dementia, and perimenopause and clinical trial methodology. The training program focuses on increasing knowledge and expertise in additional fields critical to this program of study: behavioral neuroscience, endocrinology, epidemiology, and statistics. The research proposal aims to clarify how hormonal changes during critical periods in the female reproductive life cycle might increase the risk of cognitive decline and Alzheimer's disease in later life and to develop a working hypothesis of how and when to intervene with experimental therapies aimed at preventing or limiting this outcome. The specific aims of the research plan are to: 1) determine if pregnancy is associated with measurable cognitive declines and if such declines ameliorate in the postpartum period, and 2) determine if the menopausal transition (MT) is associated with subjective and objective cognitive declines that ameliorate in menopause. Secondary aims are to determine the risk factors of cognitive impairment in the MT and to determine if cognitive impairments during the MT are predictive of age-related cognitive decline. PUBLIC HEALTH RELEVANCE: The results of these studies will lead to a greater understanding of hormonal effects on cognition throughout a woman's lifespan, with a particular emphasis on cognitive aging and risk of dementia. Further, they will clarify the trajectory of cognitive declines during reproductive events such as pregnancy and the menopausal transition, and may reveal risk factors for cognitive impairment during these events.

描述（由申请人提供）：生殖激素对大脑有几种保护作用，如促进胆碱能活性、减少神经元损失、刺激轴突发芽和树突棘形成。在本申请中，假设以显著的激素波动为特征的生殖事件（例如怀孕和绝经过渡）与可测量的认知能力下降相关，并且多个时期的雌激素耗竭增加了晚年认知能力下降和痴呆的风险。该指导以患者为导向的研究职业发展奖（K23）的总体目标是为整个生命周期中女性激素和认知研究的程序化方法奠定基础，并促进候选人发展成为独立的临床神经科学研究人员。候选人在衰老，痴呆和围绝经期神经心理学以及临床试验方法学方面拥有丰富的培训和研究经验。该培训计划的重点是增加知识和专业知识，在其他领域的关键，这个研究计划：行为神经科学，内分泌学，流行病学和统计学。该研究提案旨在阐明女性生殖生命周期关键时期的激素变化如何可能增加晚年认知能力下降和阿尔茨海默病的风险，并制定一个工作假设，即如何以及何时干预旨在预防或限制这种结果的实验疗法。研究计划的具体目标是：1）确定怀孕是否与可测量的认知下降相关，以及这种下降是否在产后期间得到改善，以及2）确定绝经过渡期（MT）是否与绝经期改善的主观和客观认知下降相关。次要目的是确定MT中认知功能障碍的风险因素，并确定MT期间的认知功能障碍是否可预测与年龄相关的认知功能下降。 公共卫生关系：这些研究的结果将使人们更好地了解荷尔蒙对女性一生中认知的影响，特别强调认知老化和痴呆症的风险。此外，他们将阐明在怀孕和绝经过渡等生殖事件期间认知下降的轨迹，并可能揭示这些事件期间认知障碍的风险因素。