Motor Function in Older Adults: the Importance of Apolipoprotein-E ε4 Inheritanc

老年人的运动功能:载脂蛋白-E ε4 遗传的重要性

基本信息

  • 批准号:
    8891343
  • 负责人:
  • 金额:
    $ 18.6万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-07-15 至 2017-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Increased age-related variability of motor function indicates that some older adults are more vulnerable to motor decline than others. Impaired motor function in vulnerable adults, leads to loss of ability to work and to lost independence, ultimately leading to substantially greater costs to an aging society. This proposal adopts a new and innovative approach to understanding motor function and motor fatigue (exercise induced reduction in strength) in vulnerable older men and women. We explore the large inter-subject variability that occurs with increased age to provide insight to a genetic mechanism underlying motor decline of the lower limb in men and women. Specifically, we associate inter-subject variability of motor function and fatigue with inheritance of the ε4 allele of the apolipoprotein-E (APOE) gene. We propose that APOE ε4 carriers have reduced effectiveness of the glutamate receptor (NMDA) in motor cortical areas and a subsequent reduction in intracortical excitability and lower neural drive during motor tasks than APOE ε4 non carriers: these mechanisms will be assessed with transcranial magnetic stimulation (TMS). Despite the substantive potential for intervention with vulnerable older adults, the cortical mechanisms underlying motor decline have received very limited attention. APOE ε4 inheritance is typically associated with risk of Alzheimer's Disease but was recently shown to increase the risk of motor function decline with advanced age. Whether motor fatigue during dynamic tasks, which is a common component of ergonomic and daily activities, exacerbates impaired strength and power in older adults with APOE ε4 inheritance is unknown. Thus, we hypothesize that impaired motor function and greater fatigue among older adults is related to possession of the APOE ε4 allele and mediated by reduced effectiveness of the glutamate receptor in motor cortical areas, reduced intracortical facilitation and decreased neural drive from motor cortical centers. Aim 1 will determine whether APOE ε4 allele possession is associated with increased motor fatigue in lower limb muscles and decreased functionality of motor tasks (walking speed, balance, stair climbing) among independently living older men and women. Aim 2 will compare intracortical facilitation and neural drive from the motor cortex during motor function tasks before and after motor fatigue among older men and women who are carriers and non-carriers of APOE ε4. Intracortical facilitation and supraspinal drive will be quantified with TMS of the motor cortex. Because older women are weaker and closer to functional performance thresholds without added vulnerability, sex differences will be explored to determine if older men or women are more vulnerable to motor impairment with APOE ε4 inheritance associated with reduced intracortical facilitation and supraspinal drive. The results will have high impact by: (1) providing insight into successful aging and the mediating role of intracortical facilitation and supraspinal drive; (2) identifying 'healthy' but vulnerable older adults for accelerated motor decline, and (3) providing a rationale for early, targeted strategies to offset altered neural networks and early motor decline.
描述(由申请人提供):与年龄相关的运动功能变异性增加表明,一些老年人比其他人更容易出现运动功能下降。弱势成年人的运动功能受损,导致丧失工作能力和失去独立性,最终导致老龄化社会的成本大幅增加。该提案采用了一种新的创新方法来了解弱势老年男性和女性的运动功能和运动疲劳(运动引起的力量下降)。我们探讨了随年龄增长而发生的较大的受试者间变异性,以深入了解男性和女性下肢运动功能下降的遗传机制。具体来说,我们将运动功能和疲劳的个体间变异性与载脂蛋白E ε4等位基因的遗传相关联。 (APOE)基因。我们认为,与APOE ε4非携带者相比,APOE ε4携带者在运动皮层区域的谷氨酸受体(NMDA)的有效性降低,随后皮质内兴奋性降低,运动任务期间的神经驱动降低:这些机制将通过经颅磁刺激(TMS)进行评估。尽管对脆弱的老年人进行干预的潜力很大,但运动功能下降的皮质机制受到的关注非常有限。APOE ε4遗传通常与阿尔茨海默病的风险相关,但最近显示随着年龄的增长,运动功能下降的风险增加。动态任务中的运动疲劳是人体工程学和日常活动的常见组成部分,是否会加剧APOE ε4遗传的老年人的力量和力量受损尚不清楚。因此,我们假设老年人的运动功能受损和更大的疲劳与APOE ε4等位基因的拥有有关,并通过运动皮质区谷氨酸受体有效性降低、皮质内易化减少和运动皮质中心神经驱动减少介导。目的1将确定APOE ε4等位基因是否与独立生活的老年男性和女性下肢肌肉运动疲劳增加和运动任务(步行速度,平衡,爬楼梯)功能下降相关。目的2将比较APOE ε4携带者和非携带者的老年男性和女性在运动疲劳前后运动功能任务期间来自运动皮层的皮质内易化和神经驱动。皮质内易化和脊髓上驱动将用运动皮质的TMS量化。由于老年女性更虚弱,更接近功能表现阈值,而不会增加脆弱性,因此将探索性别差异,以确定老年男性或女性是否更容易发生与皮质内易化和脊髓上驱动减少相关的APOE ε4遗传性运动障碍。这些结果将通过以下方式产生重大影响:(1)提供对成功衰老以及皮质内促进和脊髓上驱动的介导作用的见解;(2)识别“健康”但易受影响的老年人加速运动衰退,以及(3)提供早期有针对性的策略来抵消改变的神经网络和早期运动衰退的基本原理。

项目成果

期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Differential effects of aging and physical activity on corticospinal excitability of upper and lower limb muscles.
衰老和体力活动对上肢和下肢肌肉皮质脊髓兴奋性的不同影响。
  • DOI:
    10.1152/jn.00077.2019
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    2.5
  • 作者:
    Rozand,Vianney;Senefeld,JonathonW;Sundberg,ChristopherW;Smith,AshleighE;Hunter,SandraK
  • 通讯作者:
    Hunter,SandraK
The Relevance of Sex Differences in Performance Fatigability.
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SANDRA K HUNTER其他文献

SANDRA K HUNTER的其他文献

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{{ truncateString('SANDRA K HUNTER', 18)}}的其他基金

Mechanisms of Fatigability and the Protective Effects of Exercise in People with Diabetes
糖尿病患者的疲劳机制和运动的保护作用
  • 批准号:
    10419130
  • 财政年份:
    2022
  • 资助金额:
    $ 18.6万
  • 项目类别:
Mechanisms of Fatigability and the Protective Effects of Exercise in People with Diabetes
糖尿病患者的疲劳机制和运动的保护作用
  • 批准号:
    10705020
  • 财政年份:
    2022
  • 资助金额:
    $ 18.6万
  • 项目类别:
Motor Function in Older Adults: the Importance of Apolipoprotein-E ??4 Inheritanc
老年人的运动功能:载脂蛋白-E ??4 遗传的重要性
  • 批准号:
    8690518
  • 财政年份:
    2014
  • 资助金额:
    $ 18.6万
  • 项目类别:
Neuromuscular Fatigue: Age and Sex Differences
神经肌肉疲劳:年龄和性别差异
  • 批准号:
    8232477
  • 财政年份:
    2011
  • 资助金额:
    $ 18.6万
  • 项目类别:
Neuromuscular Fatigue in Older Adults
老年人的神经肌肉疲劳
  • 批准号:
    7515713
  • 财政年份:
    2008
  • 资助金额:
    $ 18.6万
  • 项目类别:
Task Dependence of Muscle Fatigue in Older Adults
老年人肌肉疲劳的任务依赖性
  • 批准号:
    6828507
  • 财政年份:
    2004
  • 资助金额:
    $ 18.6万
  • 项目类别:
Task Dependence of Muscle Fatigue in Older Adults
老年人肌肉疲劳的任务依赖性
  • 批准号:
    6935176
  • 财政年份:
    2004
  • 资助金额:
    $ 18.6万
  • 项目类别:

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