Blood Neurofilament Light Chain in Different Types of Dementia

Abstract

Aims: The study aimed to evaluate diagnostic values of circulating neurofilament light chain (NFL) levels in different types of dementia. Background: Previous studies reported inconsistent change of blood NFL for different types of dementia, including Alzheimer’s disease (AD), frontotemporal dementia (FTD), Parkinson’s disease dementia (PDD) and Creutzfeldt-Jakob disease (CJD) and Lewy body dementia (LBD). Objective: Meta-analysis was conducted to summarize the results of studies evaluating diagnostic values of circulating NFL levels in different types of dementia to enhance the strength of evidence. Methods: Articles evaluating change in blood NFL levels in dementia and published before July 2022 were searched on the following databases (PubMed, Web of Science, EMBASE, Medline and Google Scholar). The computed results were obtained by using STATA 12.0 software. Results: AD patients showed increased NFL concentrations in serum and plasma, compared to healthy controls (HC) [standard mean difference (SMD) = 1.09, 95% confidence interval (CI): 0.48, 1.70, I2 = 97.4%, p < 0.001]. In AD patients, higher NFL concentrations in serum and plasma were associated with reduced cerebrospinal fluid (CSF) Aβ1-42, increased CSF t-tau, increased CSF p-tau, reduced Mini-Mental State Examination (MMSE) and decreased memory. Additionally, mild cognitive impairment (MCI) showed elevated NFL concentrations in serum and plasma, compared to HC (SMD = 0.53, 95% CI: 0.18, 0.87, I2 = 93.8%, p < 0.001). However, in MCI, no significant association was found between NFL concentrations in serum, plasma and memory or visuospatial function. No significant difference was found between preclinical AD and HC (SMD = 0.18, 95% CI: -0.10, 0.47, I2 = 0.0%, p = 0.438). FTD patients showed increased NFL concentrations in serum and plasma, compared to HC (SMD = 1.08, 95% CI: 0.72, 1.43, I2 = 83.3%, p < 0.001). Higher NFL concentrations in serum and plasma were associated with increased CSF NFL in FTD. Additionally, the pooled parameters calculated were as follows: sensitivity, 0.82 (95% CI: 0.72, 0.90); specificity, 0.91 (95% CI: 0.83, 0.96). CJD patients showed increased NFL concentrations in serum and plasma, compared to HC. No significant difference in NFL level in serum and plasma was shown between AD and FTD (SMD = -0.03, 95% CI: -0.77, 0.72, I2 = 83.3%, p = 0.003). Conclusion: In conclusion, the study suggested abnormal blood NFL level in AD and MCI, but not in preclinical AD. FTD and CJD showed abnormal blood NFL levels.