PROJECT SUMMARY As the U.S. population ages, the number of people with Alzheimer’s disease and related neurodegenerative diseases (NDDs) that cause dementia will grow. Emerging disease-modifying treatments are/will be designed to address the specific biology of each form of dementia. They are likely to be most effective early in the course of illness, increasing the importance of prompt and accurate diagnosis. Specific identification of the cause of cognitive impairment is routine in Neurology and Psychiatry, but exclusive reliance on this limited workforce for assessment of cognitive and behavioral changes will result in treatment delays with meaningful clinical impact, particularly for medically underserved communities that face obstacles in accessing specialists. Early evaluation in the primary care (PC) setting can reduce delays, but PC practitioners (PCPs) identify time and a lack of confidence as barriers preventing them from assessing cognitive and behavioral complaints. Biomarkers can facilitate the identification of NDD, but expert guidelines stress that they must be paired with clinical findings to guide diagnosis. In addition, the available biomarkers only address some of the entities that cause NDD. The goal of this project is to support more thorough assessment of cognitive and behavioral complaints in PC by supporting PCPs to use a comprehensive diagnostic toolkit developed by the California Alzheimer’s Disease Centers. The toolkit includes a pre-visit questionnaire that can potentially shorten future assessments if the sensitivity of the questions can be established. This project will demonstrate first that assessment with this toolkit, in combination with regular expert-led case conferences, facilitates accurate distinction by PC providers of mild cognitive impairment and dementia likely due to Alzheimer’s disease from other, less typical NDD syndromes, and second, that the implementation of this approach is feasible and acceptable to PCPs, patients, and families. We will implement the model in five CA PC practices that work with medically underserved communities to facilitate the assessment of approximately 750 patients by at least 30 PC providers. Each participant will be re-evaluated at an expert center, where blood biomarkers of NDD will be collected. We will support PC practitioners to provide a biomarker-informed diagnostic disclosure to each patient. We will examine the accuracy of PCP diagnoses, using expert opinions and biomarkers as the gold standard, and evaluate the feasibility of toolkit use in the practices through surveys, interviews, and focus groups. To help address the sensitivity of pre-visit questions to atypical symptoms of NDD, we will also recruit 200 patients with atypical presentations at UCSF. Achievement of the project goals will establish an efficient model for earlier, etiologically-specific diagnosis of cognitive and behavioral changes due to Alzheimer’s disease and other NDDs.