Motor, Visual, and Olfactory Changes in Genetic Subtypes of Alzheimer’s Disease

标题：阿尔茨海默病遗传亚型的运动、视觉和嗅觉变化 尽管认知变化是阿尔茨海默病(AD)最显著的特征，但微妙的 感觉和运动功能的改变发生在AD病程的早期，并可能作为 生物标志物，并提供导致进展性残疾的一连串事件的线索。我们会 在一项正在进行的研究中执行基线(n=135)和3年f/u评估(n=60) 墨西哥裔常染色体携带者和常染色体高危人群连接体项目(HCP)议定书 主导(ADAD)和迟发性AD(LOAD)，以实现以下具体目标： 具体目标1)确定ADAD和ADAD中步态异常的根本原因和机制 负荷，我们将使用NIH工具箱、HCP成像协议、 用氟他西平进行tau PET成像。 具体目的1b)表征ADAD和LOAD中皮质高兴奋性的开始和过程 使用单脉冲TMS。 具体目标2a)表征ADAD患者和ADAD高危人群的临床相关视力缺陷 和使用标准化功能测量的负荷，包括基于logMAR的视力、对比度 灵敏度，以及低对比度和高对比度读取速度。 具体目标2b)通过进行高分辨率、在- 包括视网膜神经纤维层在内的中央和周围视觉通路结构的活体成像 (RNFL)、视网膜毛细血管密度、视神经/视交叉体积和外侧膝状体核(LGN) 和使用HCP的连接。 具体目标3)描述患有ADAD和ADAD高危人群的嗅觉缺陷 加载，我们将使用宾夕法尼亚大学气味识别测试(UPSIT)来评估嗅觉 并将这与tau病理和使用hcp测量的嗅觉系统的连通性有关。 ADAD和负荷的运动和感觉变化的综合特征可以识别 用于诊断、预后和治疗目标的生物标记物。 1

Title: Motor, Visual, and Olfactory Changes in Genetic Subtypes of Alzheimer's Disease Though changes in cognition are the most salient features of Alzheimer's disease (AD), subtle changes in sensation and motor function occur early in the course of AD and might serve as biomarkers and provide clues as to the cascade of events leading to progressive disability. We will perform baseline (n = 135) and 3-year f/u evaluations (n = 60) in an ongoing study using the Human Connectome Project (HCP) protocol of persons of Mexican descent with and at-risk for autosomal dominant (ADAD) and late-onset AD (LOAD) in order to achieve the following specific aims: Specific Aim 1a) To define the underlying cause and mechanisms of gait abnormalities in ADAD and LOAD, we will characterize motor and gait function using the NIH toolbox, the HCP imaging protocol, and tau PET imaging with flortaucipir. Specific Aim 1b) To characterize the onset and course of cortical hyperexcitability in ADAD and LOAD using single-pulse TMS. Specific Aim 2a) To characterize clinically relevant visual deficits in persons with and at-risk for ADAD and LOAD using standardized functional measures including logMAR based visual acuity, contrast sensitivity, as well as low and high contrast reading speed. Specific Aim 2b) To define the underlying etiology of visual deficits by performing high-resolution, in- vivo imaging of central and peripheral visual pathway structures including retinal nerve fiber layer (RNFL), retinal capillary density, volume of optic nerve/chiasm and the lateral geniculate nucleus (LGN) and connectivity using the HCP. Specific Aim 3) To characterize deficits in olfaction occurring in persons with and at-risk for ADAD and LOAD, we will assess olfaction using the University of Pennsylvania Smell Identification Test (UPSIT) and relate this to tau pathology and connectivity in the olfactory system measured using the HCP. Comprehensive characterization of motor and sensory changes in ADAD and LOAD could identify biomarkers for diagnosis, prognosis, and therapeutics targets in the management of the disease. 1