Impact of Reproductive Aging on the Functional and Structural Architecture of the Human Brain

生殖衰老对人脑功能和结构的影响

• 批准号: 10313384
• 负责人: Laura Pritschet
• 金额: $ 3.84万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-19 至 2022-09-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10313384
• 关键词: Adult; Affect; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Amyloid deposition; Animals; Applications Grants; Architecture; Area; Attention; Biological; Brain; Brain imaging; Brain region; Characteristics; Chronology; Cognition; Cognitive; Cognitive aging; Complex; Computational Technique; Disease Progression; Dorsal; Early Intervention; Endocrine; Episodic memory; Estradiol; Estrogen Receptors; Face; Female; Fogs; Functional Magnetic Resonance Imaging; Goals; Gonadal Steroid Hormones; Hippocampus (Brain); Hormone Receptor; Human; Impairment; Individual; Investigation; Knowledge; Learning; Life; Literature; Medial; Memory; Menopausal Status; Menopause; Morphology; Nerve Degeneration; Neurologic; Neuromodulator; Neurosecretory Systems; Ovarian; Ovarian hormone; Participant; Patient Self-Report; Pattern; Performance; Perimenopause; Play; Population; Postmenopause; Prefrontal Cortex; Premenopause; Prevalence; Process; Production; Progesterone; Protocols documentation; Regulation; Research; Resolution; Rest; Risk; Role; Sampling; Shapes; Stimulus; Structure; Systems Analysis; Tauopathies; Temporal Lobe; Training; Woman; Women' s Health; age related; aging brain; anatomic imaging; base; brain morphology; cingulate cortex; cognitive change; cognitive neuroscience; cognitive performance; dentate gyrus; extrastriate visual cortex; fusiform face area; hormone regulation; human old age (65+); imaging study; insight; middle age; multimodality; neural circuit; neuroimaging; neuromechanism; preservation; regional difference; relating to nervous system; reproductive; reproductive senescence; selective attention; sex; skills; symposium; targeted treatment; tool; young woman

Project Summary Despite the over-representation of women in the Alzheimer’s disease population, the influence that sex and sex steroid hormones have on the aging brain remains understudied. Over the last quarter century, the vast majority of brain imaging studies have studied the neural basis of age-related cognitive decline in adults aged 65 and older. This convention overlooks one of the most significant neuroendocrine changes in a woman’s life—the transition to menopause—and leaves a gap in our understanding of the aging brain during the critical midlife years. The menopausal transition is marked by a sweeping decline in the production of sex hormones—up to 90% in the case of 17-estradiol and progesterone. For many women, this endocrine change is accompanied by self-reported decrements in memory and attention, or “menopause fog”. Animal studies provide powerful evidence that estradiol and progesterone play a neuroprotective role in brain regions vulnerable to neurodegeneration, including the prefrontal cortex and medial temporal lobes. The degree to which female reproductive aging leads to changes in human macrostructural brain morphology, intrinsic brain network connectivity, and the neural circuits underlying higher-order cognition represents a significant knowledge gap that has yet to be adequately examined. This project will probe the effects of reproductive aging on the brain in healthy midlife women (N=90, ages 45–55), investigating the endocrine basis of neural and cognitive aging in midlife. The well-characterized sample is enriched to include a balanced distribution of pre, peri-, and post- menopausal women across a limited age range in order to isolate the effects of reproductive aging from chronological aging. This project will build on the existing menopause literature by applying state-of-the-art computational techniques to extend beyond our current understanding of fairly coarse regional differences in brain activity and morphology by menopause status. In Aim 1, I will determine how the depletion of sex hormones in midlife alters large-scale functional brain networks using resting-state fMRI and computational approaches from complex systems analysis. In Aim 2, I will use high-resolution anatomical imaging of the hippocampus and surrounding medial temporal lobe to determine whether the depletion of sex hormones impacts specific hippocampal subfields (CA1-3, dentate gyrus, subiculum) and entorhinal, perirhinal, and parahippocampal cortices, regions enriched with sex hormone receptors. In Aim 3, I will determine the effects of reproductive aging on neural mechanisms of selective attention, including the ability to suppress neural processing of irrelevant information, with the goal of elucidating the neural underpinnings of common cognitive complaints during menopause. This project will clarify the endocrine basis of age-related neural and cognitive changes, a severely understudied area in cognitive neuroscience with clear implications for women’s health.

项目摘要 尽管女性在阿尔茨海默氏病中的人数过多，但性别和性别的影响 衰老大脑的类固醇骑马仍然可以理解。在过去的四分之一世纪，绝大多数 大脑成像研究研究了65岁成年人与年龄相关的认知下降的神经基础 年龄较大。该公约忽略了女性生活中最重要的神经内分泌变化之一 - 过渡到更年期 - 并且在关键中年对衰老大脑的理解留下了差距 年。更年期的过渡以性激素生产的大幅下降为标志 - 在17-雌二醇和孕酮的情况下为90％。对于许多女性，这种内分泌变化是实现的 通过自我报告的记忆和注意力减少，或“更年期雾”。动物研究提供了强大的 雌二醇和孕酮在大脑区域中起神经保护作用的证据 神经变性，包括前额叶皮层和媒体临时爱。女性的程度 生殖衰老会导致人类宏结构脑形态的变化，内在的脑网络 连通性和高阶认知基础的神经回路代表了一个重要的知识差距 尚未得到充分检查。该项目将探测生殖衰老对大脑的影响 健康的中年妇女（n = 90，45-55岁），研究神经和认知衰老的内分泌基础 中年。特征良好的样品富含以包括前，周期和之后的平衡分布 在有限的年龄范围内的更年期妇女，以隔离生殖老化的影响 年代老化。该项目将通过应用最先进的现有更年期文献建立 计算技术超出了我们当前对相当粗糙区域差异的理解 大脑活动和形态的绝经状态。在AIM 1中，我将确定性恐怖的耗尽 在中年，使用静止状态fMRI和计算方法来改变大规模的功能性脑网络 来自复杂的系统分析。在AIM 2中，我将使用海马的高分辨率解剖成像和 周围媒体临时叶子，以确定性恐怖的耗竭是否影响特定 海马子场（CA1-3，齿状回，亚曲线）和内嗅，周围和帕拉希帕克群岛 皮质，富含性激素受体的区域。在AIM 3中，我将确定生殖衰老的影响 关于选择性注意的神经力学，包括抑制无关紧要的神经化学的能力 信息，目的是阐明在 绝经。该项目将阐明与年龄相关的神经和认知变化的内分泌基础，这是一个严重的 认知神经科学领域正在研究，对妇女健康有明显的影响。