Combination of Plasma Neurofilament Light Chain and Mini-Mental State Examination Score Predicts Progression from Mild Cognitive Impairment to Alzheimer’s Disease within 5 Years

Abstract

Background: Individuals with mild cognitive impairment (MCI) are at high risk of progression to Alzheimer’s disease (AD) dementia, but some remain stable. There is a need to identify those at higher risk of progression to improve patient management and outcomes. Objective: To evaluate the trajectory of plasma neurofilament light chain (pNFL) prior to progression from MCI to AD dementia, the performance of pNFL, in combination with the Mini-Mental State Examination (MMSE), as a predictor of progression from MCI to AD dementia and to inform clinicians on the use of pNFL as a predictive biomarker. Methods: Participants (n = 440) with MCI and longitudinal follow-up (mean = 4.2 years) from the AD Neuroimaging Initiative dataset were included. pNFL as a marker for neurodegeneration and the MMSE as a cognitive measure were investigated as simple/practical predictors of progression. The risk of progressing from MCI to AD dementia associated with pNFL and MMSE scores was assessed using Cox and logistic regression models. Results: The current risk of progression to AD dementia was 37%higher in individuals with high pNFL (> 56 ng/L) compared to those with average pNFL (≤40 ng/L). A combination of baseline pNFL and MMSE could differentiate those who progressed within 5 years (AUC = 0.75) from stable individuals. Including change in MMSE over 6-12 months further improved the model (AUC = 0.84). Conclusion: Our findings reveal that combining pNFL with a simple dementia screener (MMSE) can reliably predict whether a person with MCI is likely to progress to AD dementia within 5 years.