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: 10412042
• 负责人: Jessica Ann Bernard
• 金额: $ 54.96万
• 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/10412042
• 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; multimodal 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.

项目摘要 美国人口的迅速衰老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表现下降的因素对于帮助老年人保持其生活质量和独立性至关重要。此外，必须更好地理解与年龄相关的正常变化的模式，以查明可能表明病理学的轨迹的分歧，尤其是与阿尔茨海默氏病有关的轨迹。了解性别差异也非常重要，因为老年女性受阿尔茨海默氏病的影响不成比例，遭受了更多的跌倒，并且比老年男性更脆弱。尽管研究大脑皮层的研究扩大了我们对衰老的理解，但小脑贡献被忽略了。小脑占总大脑体积的10％，包括大脑中所有神经元的一半以上，并且是通过非侵入性大脑刺激进行干预的特别好的靶标。此外，它既有助于运动和认知功能，并且显示出老年人体积的性别差异，这可能部分归因于绝经中的马匹变化以及雌激素对小脑的作用。在调查小脑衰老的有限工作中，其容量下降仅次于海马的衰老，动物模型表明小脑感应比海马早期开始。这是大脑模型和行为变化中的小脑，这是一种创新的方法，可以提高对年龄相关性能的理解，实际上可能比单独的皮质做得更好。初步发现表明，小脑的下降可能在中年开始，并且该结构与衰老的横截面研究中的运动和认知性能有关。在这里，一个小脑，衰老和性别差异的专家团队将招募35岁以上的150名健康成年人（75名男性，75名女性），以对中年和年龄较大的小脑和行为进行了两年的纵向研究。该建议的目的是量化小脑体积，小脑 - 丘脑 - 皮层网络以及运动和认知功能，以研究小脑和行为轨迹。 AIM 1将在小脑结构和网络中量化随时间的变化，以在成年期和衰老中定义这些轨迹。 AIM 2旨在研究大脑行为的关系，并确定小脑变化与运动和认知性能下降的关系。 AIM 3将探索小脑和行为轨迹的性别差异，重点是更年期激素变化的影响。这三个目标将包括探索性分析，这些分析将研究小脑，前额叶皮层和海马的相对贡献。预期的结果对我们对衰老思想和大脑的理解产生了重大影响，并改善了我们的大脑模式和成年后的行为改变。对小脑轨迹进行调查将扩大我们对健康衰老的了解，并将为包括老年人的疾病（包括阿尔茨海默氏病）提供新的投资目标。