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

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 Neuro imaging 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). Acombination 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.

Automated summary

This study aimed to evaluate the relationship between plasma neurofilament light chain (pNFL) and disease progression, finding that MCI patients with high pNFL levels are more likely to progress to AD dementia. Combining pNFL and MMSE can predict the risk of progression for patients within 5 years, with the addition of MMSE changes assessment further improving this predictive model.