Dataset Information

Differential white matter connectivity in early mild cognitive impairment according to CSF biomarkers.

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 beta1-42 ratios.

SUBMITTER: Lim JS

PROVIDER: S-EPMC3948821 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Differential white matter connectivity in early mild cognitive impairment according to CSF biomarkers.

Lim Jae-Sung JS Park Young Ho YH Jang Jae-Won JW Park So Yong SY Kim Sangyun S

PloS one 20140310 3

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 contro ...[more]

PMID: 24614676

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Project description:Aims: To investigate the white matter (WM) integrity and hippocampal functional connectivity (FC) in type 2 diabetes mellitus (T2DM) patients without mild cognitive impairment (MCI) by using diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI), respectively. Methods: Twelve T2DM patients without MCI and 24 age, sex and education matched healthy controls (HC) were recruited. DTI and rs-fMRI data were subsequently acquired on a 3.0T MR scanner. Tract-based spatial statistics (TBSS) combining region of interests (ROIs) analysis was used to investigate the alterations of DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), λ1 and λ23) and FC measurement was performed to calculate hippocampal FC with other brain regions. Cognitive function was evaluated by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Brain volumes were also evaluated among these participants. Results: There were no difference of MMSE and MoCA scores between two groups. Neither whole brain nor regional brain volume decrease was revealed in T2DM patients without MCI. DTI analysis revealed extensive WM disruptions, especially in the body of corpus callosum (CC). Significant decreases of hippocampal FC with certain brain structures were revealed, especially with the bilateral frontal cortex. Furthermore, the decreased FA in left posterior thalamic radiation (PTR) and increased MD in the splenium of CC were closely related with the decreased hippocampal FC to caudate nucleus and frontal cortex. Conclusions: T2DM patients without MCI showed extensive WM disruptions and abnormal hippocampal FC. Moreover, the WM disruptions and abnormal hippocampal FC were closely associated. Highlights -T2DM patients without MCI demonstrated no obvious brain volume decrease.-Extensive white matter disruptions, especially within the body of corpus callosum, were revealed with DTI analysis among the T2DM patients.-Despite no MCI in T2DM patients, decreased functional connectivity between hippocampal region and some critical brain regions were detected.-The alterations in hippocampal functional connectivity were closely associated with those of the white matter structures in T2DM patients. This trial was registered to ClinicalTrials.gov (NCT02420470, https://www.clinicaltrials.gov/).

Project description:Research shows that late mild cognitive impairment (LMCI) has a high risk of turning into Alzheimer's disease (AD). Due to the invasion of detection methods and physical damage to the patients, it is not a convenient way to diagnose and detect early AD and LMCI by cerebrospinal fluid (CSF) data. So there is an urgent need to find the correlation between peripheral biological data and CSF data in the brain, and to find new diagnostic methods through changes in the peripheral biological data. Studies have shown that during the pathogenesis of LMCI and AD, peripheral immune cells specifically infiltrate into the brain through the blood-brain barrier, causing an imbalance in the brain's immune response and dysregulating the clearance of Aβ in CSF. Therefore, in this paper, canonical correlation analysis (CCA) algorithm is presented to derive the correlation between peripheral and CSF biomarkers based on LMCI peripheral gene expression data and plasma marker information. Firstly, to explore the influence of the infiltration of peripheral blood immune cells on the brain, the abundance of 28 immune cells were calculated by using the gene set enrichment analysis algorithm of LMCI samples. Then, to identify the correlation between biomarkers inside and outside of the brain, we performed CCA to calculate the relationship between CSF and peripheral biomarkers. Results of CCA showed significant correlations between the variable sets of 8 peripheral biomarkers and the variable sets of CSF biomarkers (at 0.794). Finally, according to Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis, it was found that the obtained peripheral biomarkers are involved in many immune-related pathways and functions which can be activated in peripheral blood of LMCI patients. Most related genes enriched in immune-related pathways and functions were up-regulated. Through receiver operating characteristic curve (ROC) analysis, it was also found that FP40/FP42 and type 1 T helper can accurately predict the pathological changes of LMCI (at 0.747).

Dataset Information

Differential white matter connectivity in early mild cognitive impairment according to CSF biomarkers.

Publications

Differential white matter connectivity in early mild cognitive impairment according to CSF biomarkers.

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