Novel Cognitive Markers of Early Alzheimer's Disease.

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PROJECT SUMMARY A great deal of progress has been made in identifying biomarkers that signal a preclinical phase of Alzheimer’s disease (AD) that occurs after the onset of pathophysiological processes (e.g., amyloid deposition) but prior to the appearance of clinical symptoms. While extremely valuable for disease detection, biomarker positivity does not correspond to level of cognitive functioning in preclinical AD, nor does it provide prognostic information about the timeline for future cognitive and clinical decline. There is a critical need for inexpensive and easily administered methods of detecting and staging AD as it runs its course from the preclinical to symptomatic stages. Novel neurocognitive tasks that yield early behavioral markers of AD pathology could fill this critical need. A cognitive “stress test” that could serve as a harbinger of impending decline among AD biomarker-positive individuals would be a significant contribution to the field. The proposed project will determine the diagnostic and prognostic utility of two innovative neurocognitive tasks – Visual Sensory Binding (VSB) and Visual Short Term Memory Binding (VSTMB) – as novel cognitive markers of AD pathology during the preclinical and prodromal stages of the disease. Impairment of VSB and VSTMB has previously been shown to be sensitive and specific for dementia and MCI due to AD. VSB and VSTMB are not impacted by normal aging, depression, or non-AD dementias, hence these tasks have great potential as cognitive markers to detect and stage early AD pathophysiology. To further evaluate the clinical utility of these novel tasks, they will be administered to participants from the UC San Diego Alzheimer’s Disease Research Center (ADRC) diagnosed as cognitively normal (CN) or with mild cognitive impairment (MCI). Data from the ADRC Clinical Core (clinical ratings, neuropsychological test results, APOE genotype, and CSF biomarker levels) will be used in tandem with the study-specific tasks to achieve the Aims. Specific aims of the project are (1) To demonstrate the diagnostic utility of VSB and VSTMB by comparing the performance of CN biomarker positive (CN+), CN biomarker negative (CN-) and MCI participants; (2) To determine the prognostic utility of VSB and VSTMB by evaluating their ability to predict cognitive decline; (2a) To evaluate the ability of VSB and VSTMB to measure longitudinal change; and (3) To explore the associations of VSB and VSTMB with CSF markers of synaptic function and neurodegeneration. VSB and VSTMB are easily administered, inexpensive, and noninvasive. They could aid in the detection and staging of preclinical and prodromal AD, and provide a valuable resource to clinicians and researchers who need to identify individuals with early AD or predict longitudinal decline.