Iron Status at Perimenopause: Effects on Brain and Behavior

项目概要/摘要 从初潮开始，到生育年龄，全世界有相当多的妇女 缺铁性贫血（IDA）或缺铁性贫血（ID）。ID的负面影响包括 认知和身体表现。然而，在绝经期和绝经后， 铁的状态和认知能力以及大脑健康更加模糊，关于这些的文献 尽管有证据表明，脑铁积累可能在神经系统中起作用，但这种关系是相当稀疏的。 退化和认知能力下降。 在文献中一个有趣的潜在规律是铁蛋白的全身水平之间的反比关系 以及绝经后妇女在一系列记忆任务中的表现。这表明，闭经可能会产生不同的变化，脑铁的妇女谁是ID或缺铁性贫血在或之前绝经相对 对那些没有的人。至少有两种可能性。首先，当失血停止时， 可能以与全身铁水平成反比的方式加速。对于ID女性来说，这可能会逆转任何 这些缺陷可能是由于ID，但加速了铁沉积（包括氧化应激）的负面影响， 特定的大脑区域，包括那些对注意力和记忆力至关重要的区域。第二，脑铁积累的速度可能与绝经期的铁状况无关。对于有身份证的女性来说，这意味着大脑 铁水平，虽然随着时间的推移而增加（因此，最终，扭转任何与ID相关的缺陷）将保持不变 比那些铁充足（IS）的女性更低，可能会在保护方面获得贝内。 铁积累对脑组织和功能的不利影响。 处理这些可能性的能力取决于衡量各级之间关系的可行性 血液中的铁，已知参与认知特定方面的大脑区域中的铁水平， 认知工作和休息时的动态，以及认知特定方面的行为测量。这个项目 据我们所知，这将是第一次评估评估所有这些关系的可行性。一组绝经前、绝经后和绝经后的非贫血女性，其中一半人的血铁水平较低，另一半人的血铁水平较低。 足够的，将提供结构性脑扫描，用于脑铁的区域特异性估计。他们将在 认知表现的行为测量，在大脑活动时选择性地参与这些区域 使用脑电图（EEG）测量，并且还将在两个休息时段期间记录EEG。所有 这将允许血液和脑铁之间的关系的第一个已知的定量表征 水平，大脑动力学（在工作和休息时）和行为，所有这些都与更年期的开始有关。这种横截面表征将提供有效纵向检查所急需的数据 这些问题，并将代表一个独特的贡献，现在稀疏的文学之间的关系， 铁和大脑健康以及女性晚年的认知能力。

Project summary/abstract From the onset of menarche, through the child-bearing years, a substantial number of women worldwide are challenged by iron deficiency (ID) or iron deficiency anemia (IDA). The negative effects of ID include deficits in cognitive and physical performance. At and following menopause, however, the nature of the relationship between iron status and both cognitive performance and brain health is much more ambiguous, and the literature on these relationships is quite sparse, in spite of evidence suggesting that brain iron accumulation may play a role in neural degeneration and cognitive decline. One intriguing potential regularity in the literature is an inverse relationship between systemic levels of ferritin and performance on a range of memory tasks in peri- and post-menopausal women. This suggests that amenorrhea may produce differential changes in brain iron for women who are ID or IDA at or prior to menopause relative to those who are not. There are at least two competing possibilities. First, when blood loss stops, brain iron levels may accelerate in a manner inversely proportional to systemic iron levels. For ID women, this may reverse any deficits that may be due to ID, but accelerate the negative effects of iron deposits (including oxidative stress) in specific brain regions, including those critical to attention and memory. Second, the rate of brain iron accumulation may have no relationship to iron status at menopause. For women who are ID, this would mean that brain iron levels, although increasing over time (and thus, eventually, reversing any ID-related deficits) would remain lower than those of women who are iron sufficient (IS), possibly conferring a protective benefit with respect to the adverse effects of accumulating iron on brain tissue and function. The ability to address these possibilities depends on the feasibility of measuring relationships among levels of iron in the blood, levels of iron in brain in regions known to be involved in specific aspects of cognition, brain dynamics during cognitive work and at rest, and behavioral measures of specific aspects of cognition. This project will be, to our knowledge, the first to assess the feasibility of assessing all of these relationships. A set of non-anemic pre-, peri-, and post-menopausal women, half of whom have low levels of blood iron and half of whom are sufficient, will provide structural brain scans for region-specific estimates of brain iron. They will be tested on behavioral measures of cognitive performance that selectively engage those regions while having brain activity measured using electroencephelography (EEG), and will also have EEG recorded during two periods of rest. All of this will allow for the first known quantitative characterization of the relationships among blood and brain iron levels, brain dynamics (both at work and at rest), and behavior, all relative to the onset of menopause. This cross-sectional characterization will provide the data that are critically needed for an efficient longitudinal examination of these questions, and will represent a unique contribution to a now-sparse literature on the relationship between iron and brain health and cognition in women in later life.