Cortical Inhibition and Mobility in Older Adults

老年人的皮质抑制和活动性

• 批准号: 10045129
• 负责人: Kathleen Elizabeth Hupfeld
• 金额: $ 4.25万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-02 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10045129
• 关键词: Acute; Address; Adult; Aerobic Exercise; Affect; Age; Aging; Alzheimer' s disease risk; American; Anterior; Biomechanics; Brain; Brain imaging; Cognitive; Complex; Dementia; Development; Elderly; Equilibrium; Exercise; Exercise Test; Functional disorder; Future; Gait; Glutamates; Glutamine; Goals; Health; Hospitalization; Impaired cognition; Impairment; Individual Differences; International; Intervention; Knowledge; Lead; Link; Lower Extremity; Magnetic Resonance Spectroscopy; Measures; Mediating; Mentorship; Methods; Motor; Movement; Muscle; Muscle Contraction; Neurobehavioral Manifestations; Neurosciences; Neurotransmitters; Outcome; Performance; Posture; Process; Quality of life; Reporting; Research; Research Personnel; Research Project Grants; Skeletal Muscle; Specificity; System; Testing; Training; Transcranial magnetic stimulation; Upper Extremity; Walking; Work; age difference; age effect; age related; cognitive testing; dementia risk; disability; exercise intervention; fall risk; falls; functional disability; gamma-Aminobutyric Acid; health goals; healthy aging; high risk; improved; mild cognitive impairment; mortality; motor control; motor impairment; motor symptom; novel; preservation; prevent; programs; response; restoration; therapy development; young adult

Nearly 25% of Americans age 65+ report serious mobility problems. Mobility impairments decrease quality of life and predict increased risk of falls, disability, and mortality. However, the contribution of age-related brain changes to mobility impairments is not well understood. F99 work will examine how cortical inhibitory function relates to gait and balance declines with aging. K00 work will examine the same questions in mild cognitive impairment (MCI) and test exercise as an intervention to improve cortical inhibitory function. The sponsor's (Dr. Rachael Seidler) past work supports the novel hypothesis that declines in cortical inhibitory processes at least partially underlie motor impairments with aging. For Aim 1 (F99), the candidate is collecting two measures of lower limb cortical inhibition in 30 young and 30 older adults: 1) gamma-aminobutyric acid (GABA)-edited magnetic resonance spectroscopy (MRS) and 2) transcranial magnetic stimulation-induced cortical silent period. GABA-edited MRS provides a measure of GABA neurotransmitter concentration, while cortical silent periods provide a measure of functional cortical inhibition during muscle activity. The F99 work addresses whether these two measures of cortical inhibition are reduced in older age (Aim 1a) and whether cortical inhibition relates to individual differences in gait (Aim 1b) and balance (Aim 1c). Mobility is often more impaired in MCI than in healthy aging. Motor symptoms typically arise much earlier than cognitive symptoms, and presence of motor symptoms relates to higher risk of Alzheimer's disease. Past work suggests that cortical inhibitory function is impaired in MCI and dementia, supporting that changes in cortical inhibition could be a component of MCI. Thus, for Aim 2 (K00), the candidate will work with Dr. Kirk Erickson to test whether cortical inhibition is reduced in MCI compared to healthy aging (Aim 2a) and if cortical inhibition relates to gait and balance in MCI (Aim 2b). Given relationships between cortical inhibition and motor control in healthy adults, it is feasible that cortical inhibition changes could also relate to mobility declines in MCI. Understanding neurotransmitter systems involved in mobility declines is important for development of interventions. Thus, the candidate will test whether aerobic exercise influences cortical inhibition in aging and MCI (Aim 2c). Past work demonstrated effects of exercise on cortical inhibition in young adults, but this has yet to be tested in aging or MCI. This work directly contributes to the NIA's major goals of preserving mobility in aging and studying brain changes with MCI. To successfully complete these aims, the candidate will receive extensive training from an expert mentorship team in biomechanics, brain imaging, brain stimulation, MCI, and exercise intervention work. This training will provide the candidate with a comprehensive toolkit to succeed as an aging researcher, with my future independent research program focused on: 1) determining the brain changes that contribute to motor declines in older age and MCI, and 2) identifying interventions to preserve motor function in older age and MCI.

近25%的65岁以上的美国人报告严重的流动性问题。行动障碍降低生活质量，并预测福尔斯、残疾和死亡的风险增加。然而，与年龄相关的大脑变化对移动障碍的贡献还没有得到很好的理解。F99的工作将研究皮层抑制功能如何与步态和平衡随着年龄的增长而下降。K 00工作将在轻度认知障碍（MCI）和测试运动中检查相同的问题，作为改善皮质抑制功能的干预措施。 发起人（Rachael Seidler博士）过去的工作支持了新的假设，即皮质抑制过程的下降至少部分地导致了衰老引起的运动障碍。对于目标1（F99），候选人正在收集30名年轻人和30名老年人的下肢皮层抑制的两种测量结果：1）γ-氨基丁酸（GABA）编辑的磁共振波谱（MRS）和2）经颅磁刺激诱导的皮层沉默期。GABA编辑的MRS提供了GABA神经递质浓度的测量，而皮质沉默期提供了肌肉活动期间功能性皮质抑制的测量。F99的工作解决了这两个测量皮质抑制是否在老年人中减少（目标1a），以及皮质抑制是否与步态（目标1b）和平衡（目标1c）的个体差异有关。 MCI患者的活动能力通常比健康老龄化患者受损更严重。运动症状通常比认知症状早得多，运动症状的存在与阿尔茨海默病的高风险有关。过去的工作表明，皮质抑制功能受损MCI和痴呆，支持皮质抑制的变化可能是MCI的一个组成部分。因此，对于目标2（K 00），候选人将与Kirk Erickson博士合作，以测试与健康老龄化相比，MCI中的皮质抑制是否减少（目标2a），以及皮质抑制是否与MCI中的步态和平衡有关（目标2b）。考虑到健康成年人中皮质抑制和运动控制之间的关系，皮质抑制变化也可能与MCI中的运动能力下降有关。了解参与行动能力下降的神经递质系统对于干预措施的发展非常重要。因此，候选人将测试有氧运动是否影响衰老和MCI中的皮质抑制（目标2c）。过去的工作证明了运动对年轻人大脑皮层抑制的影响，但这还有待于在衰老或MCI中进行测试。 这项工作直接有助于NIA的主要目标，即在衰老过程中保持活动能力，并研究MCI的大脑变化。为了成功完成这些目标，候选人将接受生物力学，脑成像，脑刺激，MCI和运动干预工作的专家导师团队的广泛培训。这项培训将为候选人提供一个全面的工具包，以成功地成为一名老龄化研究人员，我未来的独立研究计划集中在：1）确定大脑的变化，有助于在老年和MCI运动下降，2）确定干预措施，以保持运动功能在老年和MCI。