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.

Predicting progression to Alzheimer's disease dementia using cognitive measures

“…Change scores for TMT‐B and ADLs were the only metrics to predict AD in a multivariable model 27 . Darmanthé et al 28 . evaluated the prognostic value of plasma neurofilament light (pNfL) and MMSE to predict incident AD in ADNI patients with MCI.…”

“…Darmanthé et al28 evaluated the prognostic value of plasma neurofilament light (pNfL) and MMSE to predict incident AD in ADNI patients with MCI. The addition of MMSE change scores to a model including baseline pNfL and MMSE significantly improved the prediction of AD 28.…”

“…Darmanthé et al28 evaluated the prognostic value of plasma neurofilament light (pNfL) and MMSE to predict incident AD in ADNI patients with MCI. The addition of MMSE change scores to a model including baseline pNfL and MMSE significantly improved the prediction of AD 28. Whilst, in the present study, MMSE change scores were not predictive of incident AD, scores on a more comprehensive measure of global cognition (CAMCOG-R) were.…”

Cluster analysis dissecting cognitive deficits in older adults with major depressive disorder and the association with neurofilament light chain

“…It offered an easier way to monitor longitudinal changes without the need to obtain CSF specimen. Recent studies have revealed the implications of peripheral NfL levels to predict the progression to dementia from mild neurocognitive impairment (MCI) [ 20 – 22 ].…”

The impact of mild cognitive impairment on decision-making under explicit risk conditions: Evidence from the Personality and Total Health (PATH) Through Life longitudinal study

“…Although MCI diagnostic criteria require that activities of daily living are essentially unimpaired, functional impairments can be observed in more complex tasks, including bill paying (Griffith et al, 2003), driving (Anstey et al, 2017), and decision-making in health and financial contexts (Griffith et al, 2010; Martin et al, 2019; Okonkwo et al, 2008). A diagnosis of MCI confers an increased risk of conversion to dementia, estimated in the range of 5–10% annually (Mitchell & Shiri-Feshki, 2009), or 25–65% over a five-year period (Darmanthé, Tabatabaei-Jafari, & Cherbuin, 2021).…”