Age-related Changes in the Vestibular System and Functional Implications

描述（由申请人提供）：该项目旨在表征与年龄相关的前庭功能变化，并探讨其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) 内实现，这是一项针对超过 1000 名 20-103 岁个体的严格、全面的纵向研究。具体来说，目标 1 是描述 BLSA 人群中鳞状细胞癌和耳石功能状态以及年龄相关变异的特征，并评估这些与人口统计和共病医疗因素的关联。我们将估计每个 SCC 平面中 AVOR 增益的总体平均值和异质性（方差）以及颈部和眼部 VEMP 幅度作为年龄的函数。我们将通过人口因素（性别、种族）和合并症（糖尿病）来评估与年龄相关的鳞状细胞癌和耳石功能的差异。在目标 2 中，我们计划评估 BLSA 参与者 5 年内 SCC 和耳石功能的纵向变化，并调查人口统计和共病医疗因素的差异。 5 年内，约 600 名 BLSA 参与者将在 3-5 次重复访视中接受评估。我们将估计每个 SCC 平面中 AVOR 增益变化率以及颈部和眼部 VEMP 幅度随时间变化的平均值和异质性。我们将评估变化率是否因人口和合并症亚组而异。在目标 3 中，我们将研究鳞状细胞癌和耳石功能与年龄相关步态障碍的关系。我们还将评估改善凝视稳定性的补偿策略是否会改变 SCC 功能与年龄相关步态障碍之间的关联。我们将评估鳞状细胞癌和耳石功能以及两种重要的与年龄相关的步态障碍——步态速度慢和步态变异性增加（例如步长、宽度、速度）之间的关联，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。针对 SCC 功能丧失的一种典型的补偿策略是凝视稳定补偿性扫视。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 队列中这种补偿性扫视的频率和时间作为年龄和 AVOR 增益的函数，并研究这种扫视的早期时间是否会减少低 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描述随衰老而发生的前庭生理功能的变化，并探讨这些变化对具有临床意义的结果的影响，包括步态速度和变异性以及前庭适应在改变这些关联中的作用。拟议的工作将填补有关前庭生理功能如何随年龄变化的基础知识空白。此外，这项研究的结果将通过建立鳞状细胞癌和耳石功能的预测值范围来为临床实践提供信息 根据年龄，根据基线患者特征提供鳞状细胞癌和耳石功能的预期轨迹，以进行个体层面的患者咨询，并确定可在临床上针对的特定缺陷（例如代偿性眼跳延迟），以改善功能结果并最终降低老年人跌倒的风险。

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.