DBS-based Biomarkers of Neurodegeneration predict Cognitive Decline and Dementia Seven Years Ahead in a Large Population-Based Sample

INTRODUCTIONIt is unknown whether biomarkers of neurodegeneration collected from dried blood spots (DBS) in large-scale population settings are useful in predicting cognitive decline many years later. METHODSIn 2015, we collected DBS of 13,679 individuals aged 58 and older. All DBS were assayed for ApoE4 protein, and a smaller subsample for pTau217, GFAP, and NfL. In 2022, we obtained detailed cognition measures for 6,523 respondents. Regression analyses tested the likelihood of cognitive impairment as a function of biomarker levels. RESULTSRespondents with ApoE4 detection have worse cognitive performance seven years later as measured by six different cognitive performance measures (p<0.001). The combination of all four biomarkers is a statistically significant predictor for five cognitive performance measures, with pTau217 having the most systematic association. DISCUSSIONDBS-based biomarkers of neurodegeneration provide a cost-efficient and scalable early warning signal enabling preventive measures against AD/ADRD before the onset of serious symptoms.