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

成年期小脑的纵向研究：解剖和网络变化、运动功能和认知

• 批准号: 10170211
• 负责人: Jessica Ann Bernard
• 金额: $ 69.07万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10170211
• 关键词: Address; Adult; Age; Aging; Alzheimer' s Disease; American; Anatomy; Animal Model; Anterior; Area; Behavior; Behavioral; Brain; Cerebellum; Cerebral cortex; Cognition; Cognitive; Cross-Sectional Studies; Data; Disease; Elderly; Estrogens; Female; Future; Goals; Health; Health Care Costs; Healthcare; Healthcare Systems; Hippocampus (Brain); Hormonal Change; Human; Impaired cognition; Individual; Injury; Intervention; Investigation; Knowledge; Life Expectancy; Lobule; Longevity; Longitudinal Studies; Menopause; Modeling; Motor; Musculoskeletal Equilibrium; Neurons; Occupations; Older Population; Outcome; Pathology; Pattern; Performance; Perimenopause; Population; Postmenopause; Prefrontal Cortex; Premenopause; Process; Public Health; Publishing; Quality of life; Research; Research Personnel; Sex Differences; Signal Transduction; Societies; Structure; Targeted Research; Time; United States; Woman; Work; age related; aging brain; aging mind; base; brain behavior; brain volume; cognitive change; cognitive function; cognitive performance; design; early onset; fall risk; falls; functional decline; healthy aging; human old age (65+); improved; innovation; insight; male; middle age; motor learning; multimodality; neuroimaging; noninvasive brain stimulation; older men; older women; programs; recruit; relating to nervous system; senescence; sexual dimorphism

Project Summary The rapid aging of the population of the United States presents new challenges to our society and healthcare system. 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, particularly as related to Alzheimer’s disease. 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 and the action of estrogen on the cerebellum. In the limited work investigating the aging cerebellum, its volumetric declines are second only to those of the hippocampus, and animal models suggest that cerebellar senescence begins sooner than in 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. All three aims will include exploratory analyses that will investigate the relative contributions of the cerebellum, the prefrontal cortex, and the hippocampus. 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.

项目概要 美国人口的迅速老龄化给我们的社会和医疗保健系统带来了新的挑战。了解导致运动和认知能力下降的因素对于帮助老年人保持生活质量和独立性至关重要。此外，有必要更好地了解与年龄相关的规范变化模式，以便查明可能表明病理学的不同轨迹，特别是与阿尔茨海默病相关的轨迹。了解性别差异也非常重要，因为老年女性比老年男性更容易受到阿尔茨海默病的影响，更容易跌倒，而且更虚弱。虽然对大脑皮层的研究扩大了我们对衰老的认识，但小脑的贡献却被忽视了。小脑占大脑总体积的 10%，包含大脑中一半以上的神经元，是通过非侵入性脑刺激进行干预的特别好的目标。此外，它有助于运动和认知功能，并显示老年人体积的性别差异，这可能部分归因于更年期荷尔蒙的变化以及雌激素对小脑的作用。在研究衰老小脑的有限工作中，其体积下降仅次于海马体，动物模型表明小脑衰老比海马体开始得更早。因此，将小脑纳入大脑和行为变化模型代表了一种创新方法，可以提高对与年龄相关的性能下降的理解，并且实际上可能比单独的皮质做得更好。初步研究结果表明，小脑衰退可能从中年开始，并且在衰老的横断面研究中，该结构与运动和认知表现相关。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150名35岁以上的健康成年人（75名男性，75名女性），对中年和老年时期的小脑和行为进行为期2年的纵向研究。该提案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，以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，以定义成年期和衰老过程中的这些轨迹。目标 2 旨在研究大脑与行为的关系，并确定小脑变化与运动和认知能力下降之间的关系。目标 3 将探讨小脑和行为轨迹的性别差异，重点关注更年期荷尔蒙变化的影响。所有三个目标都将包括探索性分析，调查小脑、前额叶皮层和海马体的相对贡献。预期的结果将对我们对衰老思维和大脑的理解产生重大影响，并改善我们对成年期大脑和行为变化的模型。研究小脑轨迹将扩大我们对健康衰老的认识，并为包括阿尔茨海默病在内的与年龄相关的疾病提供新的研究目标。