The Predictive Ability of Blood Neurofilament Light Chain in Predicting Cognitive Decline in the Alzheimer’s Disease Continuum: A Systematic Review and Meta-Analysis

Abstract

Background: Alzheimer’s disease (AD) is a neurodegenerative disease with insidious onset. Identifying candidate predictors to forecast AD dementia risk before disease onset is crucial for early diagnosis and treatment. Objective: We aimed to assess the predictive ability of blood neurofilament light (NfL) chain in anticipating cognitive decline in the AD continuum. Methods: We systematically searched PubMed, Web of Science, and Embase from inception until April 7, 2023. Longitudinal observational studies examining the association between baseline blood NfL and cognitive decline or clinical disease conversion were included based on inclusion/exclusion criteria. The final effect size was represented by adjusted hazard ratios (HR) or standardized beta (s.β) coefficients with a 95% confidence interval (CI). Results: A total of 2,862 articles were identified, and 26 studies were included in this meta-analysis. The results indicated that baseline blood NfL could predict cognitive decline, with MMSE [s.β= –0.17, 95% CI (–0.26, –0.07)]; PACC [s.β= –0.09, 95% CI (–0.16, –0.03)]; ADAS-cog [s.β= 0.21, 95% CI (0.13, 0.29)]; CDR-SOB [s.β= 0.27, 95% CI (0.03, 0.50)]; Global cognitive composite [s.β= –0.05, 95% CI (–0.08, –0.01)]; Memory subdomain [s.β= –0.06, 95% CI (–0.09, –0.03)]; Language subdomain [s.β= –0.07, 95% CI (–0.10, –0.05)]; Executive function subdomain [s.β= –0.02, 95% CI (–0.03, –0.01)]; Visuospatial subdomain [s.β= –0.06, 95% CI (–0.08, –0.04)]. Additionally, baseline blood NfL could predict disease progression (conversion from CU/SCD/MCI to MCI/AD) in the AD continuum [Adjust HR = 1.32, 95% CI (1.12, 1.56)]. Conclusions: Baseline blood NfL demonstrated predictive capabilities for global cognition and its memory, language, executive function, visuospatial subdomains decline in the AD continuum. Moreover, it exhibited the potential to predict disease progression in non-AD dementia participants.