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

Abstract

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.

Declined functional connectivity of white matter during rest and working memory tasks associates with cognitive impairments in schizophrenia

“…Accordingly, in this study we extend our previous analyses (19, 21, 22) to a large cohort of patients with schizophrenia and healthy controls on both spontaneous signal during a resting state and activated signal during a spatial working memory task in order to: 1) quantitatively characterize the alterations of FC in WM affected by schizophrenia; 2) explore associations between FC in WM and cognitive functioning across the cohort; 3) further determine whether the FC alterations at WM and cognitive associates detected in schizophrenia are changed by cognitive functional loading.…”

“…Our recent work has shown that BOLD signals from WM bundles correlate with those from specific GM regions to which they connect (19, 20). Based on this correlation, we derived a WM-centered FC analysis approach and revealed that the FC at specific WM bundles declined and associated with cognitive scores in Alzheimer’s disease during resting state (21, 22).…”

Power spectra reveal distinct BOLD resting‐state time courses in white matter

“…In a resting state, the BOLD signals from white matter regions show correlations with other white and grey matter areas in a manner similar to the correlations used to infer functional connectivity between cortical volumes 21 . We, therefore, constructed the resting state matrices showing the correlations between each pair of the 80 ICs for each entire component as well as only the SP and DP portions respectively.…”

Altered Homotopic Functional Connectivity Within White Matter in the Early Stages of Alzheimer’s Disease

“…As the WM structural alterations have characterized many brain disorders, researchers have further explored the functional anomaly within WM during rest, such as schizophrenia ( Jiang et al, 2019 ), Parkinson’s disease ( Ji et al, 2019 ), and pontine strokes ( Wang et al, 2019 ). However, few studies have investigated the abnormal homotopic functional connectivity within WM (WM-HFC) in patients within the brain ( Zhao et al, 2019 ; Gao et al, 2020 ).…”