Alzheimer’s disease (AD), the most common type of dementia, imposes a substantial, global, socioeconomic burden. An estimated 6.5 million Americans aged 65 and older are living with AD, the most prevalent form of dementia. In the US, estimated health-care payments in 2022 for all patients with AD or related dementias (ADRD) amount to $345 billion. Without the means to identify high risk individuals, many will find care too little and too late: more than half of individuals with dementia or cognitive decline have not been diagnosed. There is a need for accessible and inexpensive early predictive biomarkers of memory loss and/or incident ADRDs to facilitate the early identification of high-risk individuals, providing the time necessary to make meaningful lifestyle changes to slow or prevent disease progression. This is especially important since markers like tau or beta-amyloid are primarily markers of existing, not impending disease. Emerging evidence suggests that erythrocyte (RBC) omega-3 fatty acid (FA) levels may serve as an early signal of impending disease up to 5 years before AD/ADRD develops. As a clinical laboratory that specializes in providing FA measurements, interpretation and customized behavioral interventions, OmegaQuant Analytics (OQA) supports a large and growing customer base of researchers, clinicians, businesses, and individuals. Through a partnership with the Fatty Acid Research Institute (FA expertise; biostatistical support; data access), we propose to develop a highly predictive FA-based profile using an innovative approach leveraging existing prospective cohort data. To do this, we will determine the extent to which it is possible to predict memory loss and/or incident all-cause dementia from an RBC FA signature. We will harmonize data from 19,922 individuals with assessment of incident all-cause dementia or an assessment of memory (e.g., Wechsler Memory Scale), with complete FA profile data and with an average of 10+ years of follow-up. We will then apply statistical / machine learning algorithms to determine the extent to which we can predict incident ADRD or a change in memory from FAs, with separate models for high-risk subgroups, including racial/ethnic groups [Blacks, Hispanics]. Results will be used to create a Fatty Acid Memory Index (FAMI) and Fatty Acid Dementia Index (FADI). We will create consumer-friendly interpretative reports for FAMI and FADI including actionable steps to change dietary FA behaviors to potentially modify memory loss/ dementia risk. We will determine if other clinical laboratories or clinicians are willing to pay at least $30/test (wholesale price) for each test [Profitability pathway #1 (PP#1)]. We will also determine individual consumers’ willingness to pay OQA directly $50/test (retail price per test) for either FAMI or FADI (PP#2). Proof of concept feasibility will set us up for a larger-scale prospective study and improved machine-learning/modelling in Phase II. Ultimately, we hope to generate two simple, early-warning tests that will allow for targeted intervention of individuals at high-risk for developing memory loss and/or dementia, ultimately leading to substantial reductions in the prevalence and societal burden of this disease.

Project Narrative Early identification of patients at risk for memory loss or Alzheimer’s disease related dementias (ADRD) are urgently needed so that preventive measures can be instituted early. We propose to develop and validate a blood fatty acid profile to identify disordered fatty acid patterns predictive of the development of ADRD or memory loss, using existing data from four well-respected US cohort studies. Our ultimate goal is to market a blood fatty acid profile which, either alone or in combination with other risk factors, improves the prediction of impending memory loss and/or ADRD.