Cortical Inhibition and Mobility in Older Adults

老年人的皮质抑制和活动性

• 批准号: 10544177
• 负责人: Kathleen Elizabeth Hupfeld
• 金额: $ 7.34万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 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 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10544177
• 关键词: Acute; Address; Adult; Aerobic Exercise; Affect; Age; Aging; Alzheimer' s disease risk; American; Anterior; Balance training; Biomechanics; Brain; Brain imaging; Complex; Dementia; Deterioration; Development; Elderly; Equilibrium; Exercise; Exercise Test; Functional disorder; Future; Gait; Glutamates; Glutamine; Goals; Health; Hospitalization; Impairment; Individual Differences; International; Intervention; Knowledge; Link; Longevity; Lower Extremity; Magnetic Resonance Spectroscopy; Measures; Mediating; Mentorship; Methods; Motor; Movement; Muscle; Muscle Contraction; Neurobehavioral Manifestations; Neurosciences; Neurotransmitters; Outcome; Performance; Postdoctoral Fellow; Posture; Process; Quality of life; Reporting; Research; Research Personnel; Research Project Grants; Skeletal Muscle; Specificity; Structure; 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; human old age (65+); 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% 65 岁以上的美国人表示存在严重的行动不便问题。行动障碍会降低生活质量，并导致跌倒、残疾和死亡的风险增加。然而，与年龄相关的大脑变化对行动障碍的影响尚不清楚。 F99 的工作将研究皮质抑制功能如何与步态和平衡随着衰老而下降相关。 K00 工作将检查轻度认知障碍 (MCI) 中的相同问题，并测试运动作为改善皮质抑制功能的干预措施。 申办者（Rachael Seidler 博士）过去的工作支持了这一新假设：皮质抑制过程的下降至少部分是衰老引起的运动损伤的原因。对于目标 1 (F99)，候选人正在收集 30 名年轻人和 30 名老年人的下肢皮质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质静默期。 GABA 编辑的 MRS 提供了 GABA 神经递质浓度的测量，而皮质静默期提供了肌肉活动期间功能性皮质抑制的测量。 F99 的工作探讨了这两种皮质抑制指标在老年时是否会减少（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更严重。运动症状通常比认知症状出现得早得多，并且运动症状的存在与阿尔茨海默病的较高风险有关。过去的研究表明，MCI 和痴呆症中皮质抑制功能受损，这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 (K00)，候选人将与 Kirk Erickson 博士合作，测试与健康衰老相比，MCI 中的皮质抑制是否减少（目标 2a），以及皮质抑制是否与 MCI 中的步态和平衡相关（目标 2b）。鉴于健康成人皮质抑制和运动控制之间的关系，皮质抑制的变化也可能与 MCI 的运动能力下降有关。了解与活动能力下降有关的神经递质系统对于干预措施的制定非常重要。因此，考生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皮质抑制的影响，但这尚未在衰老或 MCI 中得到测试。 这项工作直接有助于 NIA 保持衰老过程中的活动能力和利用 MCI 研究大脑变化的主要目标。为了成功完成这些目标，候选人将接受专家指导团队在生物力学、脑成像、脑刺激、MCI 和运动干预工作方面的广泛培训。这项培训将为候选人提供一个全面的工具包，帮助他们成为一名成功的老龄化研究人员，我未来的独立研究计划重点关注：1）确定导致老年和 MCI 运动衰退的大脑变化，2）确定维持老年和 MCI 运动功能的干预措施。