Elevated plasma neurofilament light (NfL) is associated with incident Alzheimer’s disease and accelerated cognitive decline in adults with Down syndrome

• DOI: 10.1002/alz.045982
• Publication Date: 2020-12-07T21:45:21Z
• Authors: Lam‐Ha T. Dang; Sharon J. Krinsky...; Sid O'Bryant; Deborah Pang; Warren B Zigman; Wayne Silverman; Nicole Schupf; Joseph H. Lee
• Keywords: Cognitive Decline

Abstract Background The value of plasma neurofilament light (NfL), a marker neurodegeneration, in Alzheimer’s Disease (AD) has been reported the general population. However, evidence for NfL as predictive neurodegeneration adults with Down Syndrome (DS) is limited. small number longitudinal studies have short follow‐up periods. Thus, prognostic indicator AD still unknown. To date, no study examined whether levels predict trajectories cognitive decline DS. In this study, we will examine association incident and decline. Method We studied 271 DS who were dementia‐free at baseline assessed 14‐ to 18‐month intervals up 5‐cycles. Baseline was measured using Simoa platform. Neuropsychological tests assessing various domains administered each visit status determined by consensus diagnosis. Cox proportional hazards models used assess between AD. Linear mixed modeling evaluate relations changes neuropsychological measures over time. Estimates adjusted age blood collection, sex, presence APOE ε4 allele, level premorbid intellectual functioning. Result Over period, 54 (21%) individuals developed mean 4.7 years. Elevated significantly associated dementia (p < 0.001); risk increases 34% per 10 pg/mL increase NfL. Participants highest quartile (41‐120 pg/mL) 8 times (95% CI: 2.5‐25.3) more likely develop AD, compared those lowest quartile. Moreover, elevated faster declines (i.e., mental status, episodic memory, visuospatial organization), but not verbal fluency construction. Conclusion accelerated subsequent Our findings suggest that may utility use routine disease monitoring clinical trial screening.