Comparing machine learning-derived MRI-based and blood-based neurodegeneration biomarkers in predicting syndromal conversion in early AD

Abstract

Introduction: We compared the machine learning-derived, MRI-based Alzheimer's disease (AD) resemblance atrophy index (AD-RAI) with plasma neurofilament light chain (NfL) level in predicting conversion of early AD among cognitively unimpaired (CU) and mild cognitive impairment (MCI) subjects.

Methods: We recruited participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) who had the following data: clinical features (age, gender, education, Montreal Cognitive Assessment [MoCA]), structural MRI, plasma biomarkers (p-tau₁₈₁ , NfL), cerebrospinal fluid biomarkers (CSF) (Aβ42, p-tau₁₈₁ ), and apolipoprotein E (APOE) ε4 genotype. We defined AD using CSF Aβ42 (A+) and p-tau₁₈₁ (T+). We defined conversion (C+) if a subject progressed to the next syndromal stage within 4 years.

Results: Of 589 participants, 96 (16.3%) were A+T+C+. AD-RAI performed better than plasma NfL when added on top of clinical features, plasma p-tau₁₈₁ , and APOE ε4 genotype (area under the curve [AUC] = 0.832 vs. AUC = 0.650 among CU, AUC = 0.853 vs. AUC = 0.805 among MCI) in predicting A+T+C+.

Discussion: AD-RAI outperformed plasma NfL in predicting syndromal conversion of early AD.

Highlights: AD-RAI outperformed plasma NfL in predicting syndromal conversion among early AD. AD-RAI showed better metrics than volumetric hippocampal measures in predicting syndromal conversion. Combining clinical features, plasma p-tau₁₈₁ and apolipoprotein E (APOE) with AD-RAI is the best model for predicting syndromal conversion.

Keywords: Alzheimer's disease; machine learning; magnetic resonance imaging; mild cognitive impairment; neurodegeneration; neurofilament light; phosphorylated tau; plasma biomarkers.