University of California, San Francisco (UCSF)

Early Markers and Brain Bases of Spatial Impairment in Alpha-Synuclein Disorders

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Spatial processing involves the perception, acquisition, organization, and utilization of location-based information, and provides a structure for how we interact with and navigate through our physical environments. Difficulties with spatial processing and navigation are among the earliest and most distressing symptoms of Parkinson’s disease and related disorders and of Alzheimer’s disease. Spatial impairments represent the most reliable aspect of observed cognitive dysfunction in transgenic mouse models of dementia, where new treatments are usually first developed. Despite the potential utility of spatial cognitive assessment tools for differential diagnosis, as outcome measures for clinical trials, and for translating basic science findings to the clinic, most neurocognitive evaluations do not measure spatial processing in a comprehensive or anatomically-specific manner. The most common method for evaluating spatial processing in a dementia evaluation is to ask the patient to copy a complex figure. Unfortunately, patients can fail this type of test due to disparate cognitive mechanisms or neuroanatomical substrates.

I aim to develop new spatial cognitive measures, including virtual reality tests of navigation, that are sensitive to the earliest cognitive changes in these disorders and that will help with early diagnosis and with monitoring disease progression and response to treatment. To develop these measures, I translate insights and methods from animal models of dementia (e.g., the Morris Water Maze). Performance on the spatial measures is correlated with multimodal neuroimaging in order to elucidate the neural substrates of spatial cognitive impairment in neurodegenerative disease. I am grateful to the Larry L. Hillblom Foundation for their generous support of this research.