Optimal combinations of CSF biomarkers for predicting cognitive decline and clinical conversion in cognitively unimpaired participants and mild cognitive impairment patients: A multi‐cohort study
Gemma Salvadó, Victoria Larsson, Karly Alex Cody, Nicholas Cullen, Erin M. Jonaitis, Erik Stomrud, Gwendlyn Kollmorgen, Norbert Wild, Sebastian Palmqvist, Shorena Janelidze, Niklas Mattsson, Henrik Zetterberg, Kaj Blennow, Sterling C. Johnson, Rik Ossenkoppele, Oskar Hansson
Abstract
INTRODUCTION: Our objective was determining the optimal combinations of cerebrospinal fluid (CSF) biomarkers for predicting disease progression in Alzheimer's disease (AD) and other neurodegenerative diseases. METHODS: We included 1,983 participants from three different cohorts with longitudinal cognitive and clinical data, and baseline CSF levels of Aβ42, Aβ40, phosphorylated tau at threonine-181 (p-tau), neurofilament light (NfL), neurogranin, α-synuclein, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), glial fibrillary acidic protein (GFAP), YKL-40, S100b, and interleukin 6 (IL-6) (Elecsys NeuroToolKit). RESULTS: ≥ 0.19) was sufficient to accurately predict change of the Mini-Mental State Examination (MMSE) in mild cognitive impairment (MCI) patients. P-tau/Aβ42 (AUC ≥ 0.87) and p-tau/Aβ42 together with NfL (AUC ≥ 0.75) were the best predictors of conversion to AD and all-cause dementia, respectively. DISCUSSION: P-tau/Aβ42 is sufficient for predicting progression in AD, with very high accuracy. Adding NfL improves the prediction of all-cause dementia conversion and cognitive decline.