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

Abstract

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