A longitudinal investigation of the cerebellum in adulthood: anatomical and network changes, motor function, and cognition

项目摘要 此处的项目摘要改编自母基金R 01 AG 064010 -01。了解因素 导致运动和认知能力下降的基因对于帮助老年人维持 生活质量和独立性。此外，更好地了解与年龄有关的规范模式， 改变是必要的，以便查明可能指示病理学的偏离轨迹。理解 性别差异也非常重要，因为老年女性受到阿尔茨海默病的影响尤其严重 疾病，遭受更多的福尔斯，比老年人更脆弱。在研究大脑 大脑皮层扩大了我们对衰老的理解，小脑的贡献却被忽视了。小脑 占大脑总体积的10%，包括大脑中一半以上的神经元，是一种 尤其是通过非侵入性脑刺激进行干预的良好目标。此外，它有助于电机和 认知功能，并显示老年人在体积上的性别差异，这可能部分是由于激素 随着更年期的变化。在有限的研究老化小脑的工作中，其体积下降是 仅次于海马体。因此，将小脑包括在大脑和行为模型中， 改变代表了一种创新的方式，以提高对年龄相关的性能下降的理解，并可能 实际上比单独的大脑皮层做得更好。初步发现表明小脑衰退可能开始 在中年期间，并且该结构与横截面中的运动和认知表现相关 老化的调查。在这里，一个由小脑、衰老和性别差异研究人员组成的专家团队将招募一名 一组150名35岁以上的健康成年人（75名男性，75名女性）进行为期2年的纵向研究， 小脑和行为之间的关系。本建议的目的是量化区域 小脑体积、小脑-丘脑-皮质网络以及运动和认知功能进行研究 小脑和行为轨迹目标1将量化小脑结构和网络随时间的变化 来定义这些在成年期和衰老期的轨迹。Aim 2旨在研究大脑行为 关系，并确定小脑的变化如何与运动和认知能力下降。目标3 将探讨小脑和行为轨迹的性别差异，重点是更年期的影响。 荷尔蒙变化预期的结果将对我们对老龄化的理解产生重大影响 心智和大脑，并改善我们的大脑模型和成年后的行为变化。研究小脑 轨迹将扩大我们对健康老龄化的认识，并为研究提供新的目标， 包括老年痴呆症在内的与年龄有关的疾病。拟议补编将支持伊万·埃雷洪先生 他的头两年的博士教育，为他提供了专门的研究时间以外的典型 教学助理职位，以及额外的深入培训。伊万将对小脑进行新颖的分析- 基底神经节连接，为他提供数据收集、处理和分析方面的培训， 作为他未来论文工作的基础。

Project Summary The project summary here is adapted from that of the parent grant R01AG064010-01. Understanding the factors that contribute to declines in both motor and cognitive performance is crucial for helping older individuals maintain their quality of life and independence. Further, a better understanding of the patterns of normative age-related change is necessary in order to pinpoint diverging trajectories that may be indicative of pathology. Understanding sex differences is also of great importance as older women are disproportionately impacted by Alzheimer’s disease, suffer from more falls, and are more frail than older men. While research investigating the cerebral cortex has expanded our understanding of aging, cerebellar contributions have been overlooked. The cerebellum makes up 10% of the total brain volume, includes more than half of all the neurons in the brain, and is an especially good target for intervention via non-invasive brain stimulation. Further, it contributes to both motor and cognitive function, and shows sex differences in volume in older adults, that may be due in part to hormonal changes with menopause. In the limited work investigating the aging cerebellum, its volumetric declines are second only to those of the hippocampus. Thus, including the cerebellum in models of brain and behavioral change represents an innovative way to improve understanding of age-related performance declines, and may in fact do a better job than the cortex alone. Preliminary findings indicate that cerebellar declines may begin during middle age, and that the structure is associated with motor and cognitive performance in cross-sectional investigations of aging. Here, an expert team of cerebellar, aging, and sex difference researchers will recruit a group of 150 healthy adults over the age of 35 (75 males, 75 females) for a 2-year longitudinal study of the cerebellum and behavior in middle age and older adulthood. The objective of this proposal is to quantify regional cerebellar volume, cerebello-thalamo-cortical networks, and motor and cognitive function to investigate cerebellar and behavioral trajectories. Aim 1 will quantify changes over time in cerebellar structure and networks to define these trajectories across adulthood and in aging. Aim 2 is designed to investigate brain-behavior relationships and determine how cerebellar changes relate to motor and cognitive performance declines. Aim 3 will explore sex differences in cerebellar and behavioral trajectories, with a focus on the influence of menopausal hormonal changes. The expected results stand to have a significant impact on our understanding of the aging mind and brain and improve our models of brain and behavioral change in adulthood. Investigating cerebellar trajectories will expand our knowledge of healthy aging and stands to provide new targets of investigation with respect to age-related diseases, including Alzheimer’s. The proposed supplement will support Mr. Ivan Herrejon for his first two years of doctoral education, providing him with dedicated research time outside of the typical teaching assistant positions, and additional in-depth training. Ivan will conduct novel analyses on cerebellar- basal ganglia connectivity, providing him training on data collection, processing and analyses, which will serve as a foundation for his future dissertation work.