Project Summary The Alzheimer’s Association’s 2019 Facts and Figures Report reports that while a cognitive assessment is required for all Medicare Annual Wellness Visit, only 16% of surveyed older adults reported having any form of memory assessment. While standardized neuropsychological tasks are sensitive to gross memory deficits, they are not as sensitive to milder deficits associated with healthy aging or early disease stages and they are often poorly suited for routine testing outside of trained neuropsychologist practitioners. Thus, there is a critical need for an easy-to administer, reliable, and sensitive measure of hippocampal memory function for clinical use. We have designed the Mnemonic Similarity Task (MST), a modified object recognition memory task, to provide not only a traditional measure of object recognition memory, but also a measure of “mnemonic discrimination” that is highly sensitive hippocampal function by placing strong demands on pattern separation. Thus, the goal of this proposal is to complete the development and validation of version of the clinical MST (cMST) as a fully encapsulated tool that would be ready for use in clinical research and for evaluation as a routine clinical tool. First, we will develop an optimized version of the MST designed for clinical use as a sensitive assay of hippocampal function that rapidly, but robustly, estimates hippocampal memory performance. The design goals are that it is: 1) easy to administer in a short amount of time, 2) has clear scoring and interpretation of results, 3) is sensitive to modest hippocampal dysfunction, 4) demonstrates reliability, and 5) exhibits general utility across a range of racial/ethnic/age groups. At the core of the MST is the use of highly similar lure items that have a range of pre-determined “mnemonic similarity” to the original studied item. We have now developed a version of the MST that uses a continuous recognition memory format and optimizes the distribution of targets, foils, and lures, along with the mnemonic similarity of those lures, for use in the cMST. Here, we will determine whether that is an ideal format or whether a Bayesian adaptive version is superior. Then we will establish normative data on the cMST across the lifespan and in early dementia. In Aim 2.1, we will evaluate the sensitivity and validity of the cMST to memory decline in healthy aging, comparing it to the standard research-grade MST and to traditional neuropsychological tests in a large lifespan sample. Repeat testing of individuals will be used to establish reliability and assess practice effects. We will use these data to create normative data. In Aim 2.2, we will extend these investigations to clinical populations - specifically to those with Mild Cognitive Impairment or early AD through the UCI Alzheimer’s Disease Research Center (ADRC) to determine both viability and normative performance of our measures in these impaired populations and diagnostic ability of the cMST. B...