Age-related Changes in the Vestibular System and Functional Implications

描述(由申请人提供)：该项目旨在描述与年龄相关的前庭功能变化，并探索它们对增加老年人跌倒风险和死亡率的重要步态结果的影响。这些目标将在巴尔的摩老龄化纵向研究(BLSA)中实现，这是一项对20-103岁的1000人进行的严格、全面的纵向研究。具体地说，目标1是描述BLSA人群中鳞状细胞癌和耳石的功能状态和年龄相关的变异，并评估这些与人口统计学和并存的医学因素的相关性。我们将估计每个鳞状细胞癌平面和颈部和眼部VEMP波幅随年龄变化的总体均值和AVOR增益的异质性(方差)。我们将通过人口统计因素(性别、种族)和合并症(糖尿病)来评估与年龄相关的SCC和耳石功能的差异。在目标2中，我们计划评估BLSA参与者在5年内SCC和耳石功能的纵向变化，并调查人口统计学和并存的医学因素的差异。在5年内，约600名BLSA参与者将在3-5次重复访问中接受评估。我们将评估每个鳞状细胞癌平面内AVOR增益变化率的平均值和异质性，以及颈部和眼部VEMP幅度随时间的变化。我们将评估变化率是否因人口统计学和共病亚组不同而不同。在目标3中，我们将调查鳞状细胞癌和耳石功能与年龄相关步态障碍的关系。我们还将评估提高凝视稳定性的代偿策略是否改变了SCC功能和年龄相关步态损害之间的联系。我们将评估SCC和耳石功能与两种重要的与年龄相关的步态障碍-步态速度缓慢和步态变异性增加(例如步长、步幅、步速)之间的关系，控制潜在的混杂因素，包括踝关节本体感觉、视力、下肢力量和神经认知功能。对于SCC功能丧失的一个很好的补偿策略是稳定凝视的补偿性眼跳。重要的是，这种眼跳可以通过前庭康复来诱导和改善。我们将评估BLSA队列中这种代偿性眼跳的频率和时间作为年龄和avor增益的函数，并调查这种眼跳的早期时间是否减少了低avor增益对步态速度和变异性的影响。这项工作代表了一种跨学科的方法来表征随着年龄增长而发生的前庭生理功能的变化，并探索这些变化对包括步态速度和可变性在内的临床显著结果的影响，以及前庭适应在改变这些关联中的作用。这项拟议的工作将填补关于前庭生理功能如何随年龄变化的基本知识空白。此外，这项研究的结果将通过建立鳞癌和耳石功能的预测值范围来指导临床实践。 通过根据个人水平的患者咨询的基线患者特征提供SCC和耳石功能的预期轨迹，以及通过识别特定的缺陷(例如，代偿性眼跳延迟)，可以在临床上针对这些缺陷来改善功能结果，并最终降低老年人的跌倒风险。

DESCRIPTION (provided by applicant): This project aims to characterize age-related changes in vestibular function, and explore their influence on important gait outcomes that increase fall risk and mortality in older individuals. These aims will be carried out within the Baltimore Longitudinal Study of Aging (BLSA), a rigorous, comprehensive longitudinal study of >1000 individuals age 20-103. Specifically, Aim 1 is to characterize SCC and otolith functional status and age- related variation in the BLSA population, and evaluate these for associations with demographic and comorbid medical factors. We will estimate population means and heterogeneity (variance) in AVOR gain in each SCC plane and cervical and ocular VEMP amplitudes as a function of age. We will evaluate differences in age- related SCC and otolith function by demographic factors (gender, race) and comorbidities (diabetes). In Aim 2, we plan to evaluate longitudinal changes in SCC and otolith function within BLSA participants over 5 years and investigate differences by demographic and comorbid medical factors. In 5 years, ~600 BLSA participants will be evaluated at 3-5 repeated visits. We will estimate mean and heterogeneity in rate of change of AVOR gain in each SCC plane and cervical and ocular VEMP amplitudes as a function of time. We will assess whether rates of change differ by demographic and comorbidity subgroups. In Aim 3, we will investigate the association of SCC and otolith function with age-related gait impairment. We will also evaluate whether a compensatory strategy that improves gaze stabilization modifies the association between SCC function and age-related gait impairment. We will evaluate associations between SCC and otolith function and two important age-related gait impairments - slow gait speed and increased gait variability (e.g. in step length, width, velocity), controlling for potential confounders including ankle proprioception, vision, lower extremity strength and neurocognitive function. A well-characterized compensatory strategy for SCC function loss is the gaze-stabilizing compensatory saccade. Importantly, this saccade can be induced and improved through vestibular rehabilitation. We will evaluate the frequency and timing of this compensatory saccade in the BLSA cohort as a function of age and AVOR gain, and investigate whether early timing of this saccade reduces the impact of low AVOR gain on gait speed and variability. This work represents an interdisciplinary approach to characterize the changes in vestibular physiologic function that occur with aging, and to explore the impact of these changes on clinically-significant outcomes including gait speed and variability and the role of vestibular adaptation in modifying these associations. The proposed work will fill fundamental knowledge gaps about how vestibular physiologic function changes with age. Moreover, findings from this study will inform clinical practice by establishing the range of predicted values for SCC and otolith function by age, by providing expected trajectories for SCC and otolith function according to baseline patient characteristics for individual- level patient counseling, and by identifying specific deficts (e.g. delay of compensatory saccades) that can be targeted clinically to improve functional outcomes and ultimately reduce fall risk in older individuals.