Abstract

Purpose: To investigate the brain information flow pattern in patients with early mild cognitive impairment (EMCI) and explore its potential ability of differentiation and prediction for EMCI.Methods: In this study, 49 patients with EMCI and 40 age- and sex-matched healthy controls (HCs) with available resting-state functional MRI images and neurological measures [including the neuropsychological evaluation and cerebrospinal fluid (CSF) biomarkers] were included from the Alzheimer's Disease Neuroimaging Initiative. Functional MRI measures including preferred information flow direction between brain regions and preferred information flow index of each brain region parcellated by the Atlas of Intrinsic Connectivity of Homotopic Areas (AICHA) were calculated by using non-parametric multiplicative regression-Granger causality analysis (NPMR-GCA). Edge- and node-wise Student's t-test was conducted for between-group comparison. Support vector classification was performed to differentiate EMCI from HC. The least absolute shrinkage and selection operator (lasso) regression were used to evaluate the predictive ability of information flow measures for the neurological state.Results: Compared to HC, disturbed preferred information flow directions between brain regions involving default mode network (DMN), executive control network (ECN), somatomotor network (SMN), and visual network (VN) were observed in patients with EMCI. An altered preferred information flow index in several brain regions (including the thalamus, posterior cingulate, and precentral gyrus) was also observed. Classification accuracy of 80% for differentiating patients with EMCI from HC was achieved by using the preferred information flow directions. The preferred information flow directions have a good ability to predict memory and executive function, level of amyloid β, tau protein, and phosphorylated tau protein with the high Pearson's correlation coefficients (r > 0.7) between predictive and actual neurological measures.Conclusion: Patients with EMCI were presented with a disturbed brain information flow pattern, which could help clinicians to identify patients with EMCI and assess their neurological state.

Highlights

  • Mild cognitive impairment (EMCI) has been considered as the mildest neuropsychological impairment state preceding Alzheimer’s disease (AD) [1]

  • Classification accuracy of 80% for differentiating patients with Early mild cognitive impairment (EMCI) from healthy controls (HCs) was achieved by using the preferred information flow directions

  • No difference was observed on age, sex, Alzheimer’s Disease Neuroimaging Initiative (ADNI)-EF, amyloid β (Aβ), Tau, and phosphorylated tau (pTau) between EMCI and HC

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Summary

Introduction

Mild cognitive impairment (EMCI) has been considered as the mildest neuropsychological impairment (including memory and cognitive deficit) state preceding Alzheimer’s disease (AD) [1]. The clinical manifestations of EMCI include mild loss of motor functions, speech difficulties, memory concerns, and decreased ability to read and write, which could be observed in the normal elderly population as well, making it difficult for clinical diagnosis [2,3,4,5]. Serologic tests, cerebrospinal fluid (CSF) biomarkers, and genotypes contribute to early identification of EMCI and assessment of neurological state [6,7,8,9]. Noninvasive objective biomarkers were warranted to accurately differentiate EMCI from normal elders and assess the neurological state (e.g., cognitive state and CSF biomarker levels)

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