Differential White Matter Connectivity in Early Mild Cognitive Impairment According to CSF Biomarkers

Jae-Sung Lim,Sangyun Kim,Jae-Won Jang,Young Ho Park,So Yong Park,Karl Herholz

doi:10.1371/journal.pone.0091400

Abstract

Mild cognitive impairment (MCI) is a heterogeneous group and certain MCI subsets eventually convert to dementia. Cerebrospinal fluid (CSF) biomarkers are known to predict this conversion. We sought evidence for the differences in white matter connectivity between early amnestic MCI (EMCI) subgroups according to a CSF phosphorylated tau181p/amyloid beta1–42 ratio of 0.10. From the Alzheimer's Disease Neuroimaging Initiative database, 16 high-ratio, 25 low-ratio EMCI patients, and 20 normal controls with diffusion tensor images and CSF profiles were included. Compared to the high-ratio group, radial diffusivity significantly increased in both sides of the corpus callosum and the superior and inferior longitudinal fasciculus in the low-ratio group. In widespread white matter skeleton regions, the low-ratio group showed significantly increased mean, axial, and radial diffusivity compared to normal controls. However, the high-ratio group showed no differences when compared to the normal group. In conclusion, our study revealed that there were significant differences in white matter connectivity between EMCI subgroups according to CSF phosphorylated tau181p/amyloid beta1–42ratios.

Highlights

Mild cognitive impairment (MCI) is a heterogeneous group, and certain subsets eventually convert to dementia [1]
After excluding 6 subjects with old lacunar infarction or significant white matter hyperintensities, a total of 61 early amnestic MCI (EMCI) and normal subjects (16 high-ratio, 25 low-ratio, 20 normal controls) with Diffusion tensor images (DTI) and Cerebrospinal fluid (CSF) profiles were included from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (Figure 1)
In corrected images for multiple comparisons, we found that DR of the low-ratio group was significantly increased in both sides of the corpus callosum, forceps minor, and superior and inferior longitudinal fasciculus after adjusting for covariates compared to the high-ratio group (Figure 2)

Summary

Introduction

Mild cognitive impairment (MCI) is a heterogeneous group, and certain subsets eventually convert to dementia [1]. Cerebrospinal fluid (CSF) Amyloid beta peptides 1–42 (Ab1–42) are considered as an early indicator of AD conversion compared to CSF tau [4]. Though decreased CSF Ab1–42 levels usually accompany high-tau groups, Ab1–42 levels may show variable concentrations even with similar tau levels, especially in early amnestic MCI or stable MCI [5,6]. Considering that there are heterogeneous subsets in MCI, this variability brought up questions about grouping MCI based on absolute values of CSF total tau, even with age-attributed norm data [7,8]. We thought both CSF Ab1–42 and tau should be simultaneously considered to optimally classify MCI subgroups

Methods

Results

Conclusion