Dataset Information

Functional connectivity of white matter as a biomarker of cognitive decline in Alzheimer's disease.

ABSTRACT: OBJECTIVE:In vivo functional changes in white matter during the progression of Alzheimer's disease (AD) have not been previously reported. Our objectives are to measure changes in white matter functional connectivity (FC) in an elderly population undergoing cognitive decline as AD develops, to establish their relationship to neuropsychological scores of cognitive abilities, and to assess the performance in prediction of AD using white matter FC measures as features. METHODS:Analyses were conducted using resting state functional MRI and neuropsychological data from 383 ADNI participants, including 136 cognitive normal (CN) controls, 46 with significant memory concern, 83 with early mild cognitive impairment (MCI), 37 with MCI, 46 with late MCI, and 35 with AD dementia. FC metrics between segregated white matter tracts and discrete gray matter volumes or between white matter tracts were quantitatively analyzed and characterized, along with their relationships to 6 cognitive measures. Finally, supervised machine learning was implemented on white matter FCs to classify the participants and performance of the classification was evaluated. RESULTS:Significant decreases in FC measures were found in white matter with prominent, specific, regional deficits appearing in late MCI and AD dementia patients from CN. These changes significantly correlated with neuropsychological measurements of impairments in cognition and memory. The sensitivity and specificity of distinguishing AD dementia and CN using white matter FCs were 0.83 and 0.81 respectively. CONCLUSIONS AND RELEVANCE:The white matter FC decreased in late MCI and AD dementia patients compared to CN participants, and this decrease was correlated with cognitive measures. White matter FC is valuable in the prediction of AD. All these findings suggest that white matter FC may be a promising avenue for understanding functional impairments in white matter tracts during AD progression.

SUBMITTER: Gao Y

PROVIDER: S-EPMC7567362 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Functional connectivity of white matter as a biomarker of cognitive decline in Alzheimer's disease.

Gao Yurui Y Sengupta Anirban A Li Muwei M Zu Zhongliang Z Rogers Baxter P BP Anderson Adam W AW Ding Zhaohua Z Gore John C JC

PloS one 20201016 10

<h4>Objective</h4>In vivo functional changes in white matter during the progression of Alzheimer's disease (AD) have not been previously reported. Our objectives are to measure changes in white matter functional connectivity (FC) in an elderly population undergoing cognitive decline as AD develops, to establish their relationship to neuropsychological scores of cognitive abilities, and to assess the performance in prediction of AD using white matter FC measures as features.<h4>Methods</h4>Analys ...[more]

PMID: 33064765

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Project description:While cerebrovascular disease can be observed in vivo using MRI, the multiplicity and heterogeneity in the mechanisms of cerebrovascular damage impede accounting for these measures in ageing and dementia studies. Our primary goal was to investigate the key sources of variability across MRI markers of cerebrovascular disease and evaluate their impact in comparison to amyloidosis on cognitive decline in a population-based sample. Our secondary goal was to evaluate the prognostic utility of a cerebrovascular summary measure from all markers. We included both visible lesions seen on MRI (white matter hyperintensities, cortical and subcortical infarctions, lobar and deep microbleeds) and early white matter damage due to systemic vascular health using diffusion changes in the genu of the corpus callosum. We identified 1089 individuals aged ≥60 years with concurrent amyloid-PET and MRI scans from the population-based Mayo Clinic Study of Aging. We divided these into discovery and validation datasets. Using the discovery dataset, we conducted principal component analyses and ascertained the main sources of variability in cerebrovascular disease markers. Using linear regression and mixed effect models, we evaluated the utility of these principal components and combinations of these components for the prediction of cognitive performance along with amyloidosis. Our main findings were (i) there were three primary sources of variability among the CVD measures-white matter changes are driven by white matter hyperintensities and diffusion changes; number of microbleeds (lobar and deep); and number of infarctions (cortical and subcortical); (ii) Components of white matter changes and microbleeds but not infarctions significantly predicted cognition trajectories in all domains with greater contributions from white matter; and (iii) The summary vascular score explained 3-5% of variability in baseline global cognition in comparison to 3-6% variability explained by amyloidosis. Across all cognitive domains, the vascular summary score had the least impact on memory performance (∼1%). Though there is mechanistic heterogeneity in the cerebrovascular disease markers measured on MRI, these changes can be grouped into three components and together explain variability in cognitive performance equivalent to the impact of amyloidosis on cognition. White matter changes represent dynamic ongoing damage, predicts future cognitive decline across all domains and diffusion measurements help capture white matter damage due to systemic vascular changes. Therefore, measuring and accounting for white matter changes using diffusion MRI and white matter hyperintensities along with microbleeds will allow us to capture vascular contributions to cognitive impairment and dementia.

Project description:BackgroundWhite matter hyperintensity (WMH) is one of the typical neuroimaging manifestations of cerebral small vessel disease (CSVD), and the WMH correlates closely to cognitive impairment (CI). CSVD patients with WMH own altered topological properties of brain functional network, which is a possible mechanism that leads to CI. This study aims to identify differences in the characteristics of some brain functional network among patients with different grades of WMH and estimates the correlations between these different brain functional network characteristics and cognitive assessment scores.Methods110 CSVD patients underwent 3.0 T Magnetic resonance imaging scans and neuropsychological cognitive assessments. WMH of each participant was graded on the basis of Fazekas grade scale and was divided into two groups: (A) WMH score of 1-2 points (n = 64), (B) WMH score of 3-6 points (n = 46). Topological indexes of brain functional network were analyzed using graph-theoretical method. T-test and Mann-Whitney U test was used to compare the differences in topological properties of brain functional network between groups. Partial correlation analysis was applied to explore the relationship between different topological properties of brain functional networks and overall cognitive function.ResultsPatients with high WMH scores exhibited decreased clustering coefficient values, global and local network efficiency along with increased shortest path length on whole brain level as well as decreased nodal efficiency in some brain regions on nodal level (p < 0.05). Nodal efficiency in the left lingual gyrus was significantly positively correlated with patients' total Montreal Cognitive Assessment (MoCA) scores (p < 0.05). No significant difference was found between two groups on the aspect of total MoCA and Mini-mental State Examination (MMSE) scores (p > 0.05).ConclusionTherefore, we come to conclusions that patients with high WMH scores showed less optimized small-world networks compared to patients with low WMH scores. Global and local network efficiency on the whole-brain level, as well as nodal efficiency in certain brain regions on the nodal level, can be viewed as markers to reflect the course of WMH.

Dataset Information

Functional connectivity of white matter as a biomarker of cognitive decline in Alzheimer's disease.

Publications

Functional connectivity of white matter as a biomarker of cognitive decline in Alzheimer's disease.

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