Episodic Memory-Related Imaging Features as Valuable Biomarkers for the Diagnosis of Alzheimer's Disease: A Multicenter Study Based on Machine Learning

Abstract

Background: Individualized and reliable biomarkers are crucial for diagnosing Alzheimer's disease (AD). However, lack of accessibility and neurobiological correlation are the main obstacles to their clinical application. Machine learning algorithms can effectively identify personalized biomarkers based on the prominent symptoms of AD.

Methods: Episodic memory-related magnetic resonance imaging (MRI) features of 143 patients with amnesic mild cognitive impairment (MCI) were identified using a multivariate relevance vector regression algorithm. The support vector machine classification model was constructed using these MRI features and verified in 2 independent datasets (N = 994). The neurobiological basis was also investigated based on cognitive assessments, neuropathologic biomarkers of cerebrospinal fluid, and positron emission tomography images of amyloid-β plaques.

Results: The combination of gray matter volume and amplitude of low-frequency fluctuation MRI features accurately predicted episodic memory impairment in individual patients with amnesic MCI (r = 0.638) when measured using an episodic memory assessment panel. The MRI features that contributed to episodic memory prediction were primarily distributed across the default mode network and limbic network. The classification model based on these features distinguished patients with AD from normal control subjects with more than 86% accuracy. Furthermore, most identified episodic memory-related regions showed significantly different amyloid-β positron emission tomography measurements among the AD, MCI, and normal control groups. Moreover, the classification outputs significantly correlated with cognitive assessment scores and cerebrospinal fluid pathological biomarkers' levels in the MCI and AD groups.

Conclusions: Neuroimaging features can reflect individual episodic memory function and serve as potential diagnostic biomarkers of AD.

Keywords: Alzheimer’s disease; Biomarker; Classification; Episodic memory; Machine learning; Magnetic resonance imaging.