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
Affiliations: [a]
ANU Medical School, Australian National University, Canberra, Australia
| [b]
Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, Australia
Correspondence:
[*]
Correspondence to: Nicolas Cherbuin, PhD, Centre for Research on Ageing, Health and Wellbeing, Australian National University, Florey Building 54, Mills Road, Acton, ACT 2601 Australia. E-mail: nicolas.cherbuin@anu.edu.au.
Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
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.
