Cerebrospinal fluid neurofilament light predicts the rate of executive function decline in younger-onset dementia

Introduction: Determining disease severity and predicting prognosis in younger onset-dementia (YOD) remains challenging. Whether CSF biomarkers neurofilament light (NfL), tau and amyloidβ 42 (Aβ42) can help provide such information has been underexplored.

Methods: Patients with YOD and CSF analysis were identified. We compared baseline NfL, tau and Aβ42 concentrations with contemporaneous Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG) scores to assess their association with severity of cognitive impairment. Cognitive decline, as measured by longitudinal NUCOG assessment, was correlated against baseline biomarker levels to assess their utility in predicting the rate of cognitive decline.

Results: 78 patients with YOD (mean age = 56 years, SD = 8) and CSF analysis were identified. Dementia types included Alzheimer's disease, behavioural variant frontotemporal dementia, dementia not-otherwise-specified and other. Tau was associated with contemporaneous memory dysfunction (r = -0.556, 95% CI:[-0.702,-0.393], p < .001). 21 patients had longitudinal cognitive assessment up to 82 months from CSF sampling. NfL was associated with the rate of executive function decline (r = 0.755, 95% CI:[0.259,0.937], p < .001). Aβ42 was associated with the rate of memory decline (r = -0.582, 95% CI:[-0.855,-0.274], p = .007) and rate of total NUCOG decline (r = -0.515, 95% CI: [-0.809, -0.227], p = .017).

Conclusion: CSF tau is related to contemporaneous memory impairment in YOD. NfL and Aβ42 levels are associated with the rate of executive function and memory decline, respectively, and may have a role in prognostication in YOD.