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

阿尔茨海默病遗传亚型的运动、视觉和嗅觉变化

• 批准号: 10549307
• 负责人: JOHN M RINGMAN
• 金额: $ 82.08万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10549307
• 关键词: Aging; Alzheimer' s Disease; Amyloid; Anatomy; Anosmia; Biological Markers; Blood Vessels; Blood capillaries; CNS degeneration; Cessation of life; Clinical; Cognition; Contrast Sensitivity; Deposition; Deterioration; Development; Diagnosis; Differential Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease Management; Disease Progression; Equilibrium; Esthesia; Etiology; Evaluation; Event; Future; Gait; Gait abnormality; Genetic; Glaucoma; Human; Image; Knowledge; Late Onset Alzheimer Disease; Lateral Geniculate Body; Macular degeneration; Measurable; Measures; Memory; Mexican; Modeling; Motor; Motor Cortex; Musculoskeletal System; Mutation; Nature; Odors; Olfactory Pathways; Optic Nerve; Optics; Pathology; Pennsylvania; Peripheral; Peripheral Nervous System Diseases; Persons; Photophobia; Physiologic pulse; Polyneuropathy; Positron-Emission Tomography; Prognosis; Protocols documentation; Radiation; Reading; Resolution; Retina; Risk; Sensory; Smell Perception; Speed; Standardization; Structure; Symptoms; Testing; Thick; Thinking; Thinness; United States National Institutes of Health; Universities; Vision; Visual; Visual Acuity; Visual Pathways; Visual System; autosomal dominant Alzheimer' s disease; autosome; biomarker identification; clinically relevant; comorbidity; connectome; density; disability; falls; ganglion cell; in vivo imaging; motor deficit; mutational status; pre-clinical; presenilin-1; retinal nerve fiber layer; senescence; tau Proteins; therapeutic target; walking speed

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

题目：阿尔茨海默病遗传亚型的运动、视觉和嗅觉变化