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 1 a) 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 1 b) To characterize the onset and course of cortical hyperexcitability in ADAD and LOAD using single-pulse TMS.
Specific Aim 2 a) 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 2 b) 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

Public Health Relevance

Changes in memory and thinking are the most common early symptoms of Alzheimer's disease (AD) but there is also evidence that changes in sensory and motor function also occur early in the course of AD. Greater knowledge of these changes might help us better understand the nature of degeneration of the central nervous system that is occurring in AD and also identify markers of diagnosis and progression of the disease. In the current project we will perform comprehensive clinical and imaging assessments of gait and motor function, vision and the visual system, and olfaction in persons with and destined to develop both a predictable genetic form of AD (autosomal dominant AD, or ADAD) and the much more common late-onset AD (LOAD) in order to characterize the nature and timing of such changes.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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St Hillaire-Clarke, Coryse
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University of Southern California
Schools of Medicine
Los Angeles
United States
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