Abstract
BackgroundNeurofilament light chain (NFL) level has been suggested as a blood-based biomarker for neurodegeneration in dementia. However, the association between baseline NFL levels and cognitive stage transition or cortical thickness is unclear. This study aimed to investigate whether baseline NFL levels are associated with cognitive stage transition or cortical thickness in mild cognitive impairment (MCI) and cognitively unimpaired (CU) participants.MethodsThis study analyzed data on participants from the independent validation cohort of the Korea Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (KBASE-V) study. Among the participants of KBASE-V study, 53 MCI and 146 CU participants who were followed up for ≥ 2 years and had data on the serum NFL levels were eligible for inclusion in this study. Participants were classified into three groups according to baseline serum NFL levels of low, middle, or high.ResultsThe Kaplan–Meier analysis showed association between the serum NFL tertiles and risk of cognitive stage transition in MCI (P = 0.002) and CU (P = 0.028) participants, analyzed separately. The same is true upon analysis of MCI and CU participants together (P < 0.001). In MCI participants, the highest serum NFL tertile and amyloid-beta positivity were independent predictors for cognitive stage transition after adjusting for covariates. For CU participants, only amyloid-beta positivity was identified to be an independent predictor.ConclusionThe study shows that higher serum NFL tertile levels correlate with increased risk of cognitive stage transition in both MCI and CU participants. Serum NFL levels were negatively correlated with the mean cortical thickness of the whole-brain and specific brain regions.
Highlights
Neurofilament light chain (NFL) level has been suggested as a blood-based biomarker for neurodegen‐ eration in dementia
mild cognitive impairment (MCI) participants met the core clinical criteria for MCI due to Alzheimer’s disease (AD) established by the National Institute on Aging-Alzheimer’s Association (NIA-AA) workgroups [12] and the following criteria modified from the criteria proposed by Petersen et al [13]: (1) Clinical Dementia Rating (CDR) scale score of 0.5, (2) memory complaints by patients, caregivers, or clinicians; (3) a performance score < 1.5 Standard deviation (SD) below the age, education, and sex-adjusted normative means for one or more of the four memory tests included in the CERAD, (4) the ability to perform independent activities of daily living (ADL) [14], and (5) absence of dementia
Among the 146 cognitively unimpaired (CU) participants, 14 (9.6%) participants progressed to MCI and two (1.4%) participants progressed to dementia
Summary
Neurofilament light chain (NFL) level has been suggested as a blood-based biomarker for neurodegen‐ eration in dementia. The association between baseline NFL levels and cognitive stage transition or cortical thickness is unclear. This study aimed to investigate whether baseline NFL levels are associated with cognitive stage transition or cortical thickness in mild cognitive impairment (MCI) and cognitively unimpaired (CU) participants. (MRI), positron emission tomography (PET) amyloid imaging, or cerebrospinal fluid (CSF) studies, which are expensive and/or invasive. It is unclear whether individuals with brain atrophy and/or Aβ positivity will develop dementia during their lifetime. Neurofilament light chain (NFL) level has been proposed as a blood biomarker that can overcome these limitations [4]
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