Causal structural covariance network revealing atrophy progression in Alzheimer's disease continuum

Qing, Zhao; Feng, Chen; Lu, Jiaming; Lv, Pin; Li, Weiping; Liang, Xue; Wang, Maoxue; Wang, Zhengge; Zhang, Xin; Zhang, Bing

doi:10.1002/hbm.25531

Cited by 19 publications

(11 citation statements)

References 51 publications

(81 reference statements)

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“…The MCI group in the present study showed an increased small-word property compared to the SCD group. Consistent with this, a recent study conducted on 194 elderly subjects with records on amyloid and tau status also suggested that the structural covariance was enhanced during AD progression [ 79 ]. Increased structural covariance seeding from hippocampal subfields and basal forebrain in MCI patients has been reported by the voxel-based analysis [ 80 , 81 ].…”

Section: Discussionsupporting

confidence: 61%

Spatial navigation is associated with subcortical alterations and progression risk in subjective cognitive decline

Chen

Long

et al. 2023

Alz Res Therapy

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Background Subjective cognitive decline (SCD) may serve as a symptomatic indicator for preclinical Alzheimer’s disease; however, SCD is a heterogeneous entity regarding clinical progression. We aimed to investigate whether spatial navigation could reveal subcortical structural alterations and the risk of progression to objective cognitive impairment in SCD individuals. Methods One hundred and eighty participants were enrolled: those with SCD (n = 80), normal controls (NCs, n = 77), and mild cognitive impairment (MCI, n = 23). SCD participants were further divided into the SCD-good (G-SCD, n = 40) group and the SCD-bad (B-SCD, n = 40) group according to their spatial navigation performance. Volumes of subcortical structures were calculated and compared among the four groups, including basal forebrain, thalamus, caudate, putamen, pallidum, hippocampus, amygdala, and accumbens. Topological properties of the subcortical structural covariance network were also calculated. With an interval of 1.5 years ± 12 months of follow-up, the progression rate to MCI was compared between the G-SCD and B-SCD groups. Results Volumes of the basal forebrain, the right hippocampus, and their respective subfields differed significantly among the four groups (p < 0.05, false discovery rate corrected). The B-SCD group showed lower volumes in the basal forebrain than the G-SCD group, especially in the Ch4p and Ch4a-i subfields. Furthermore, the structural covariance network of the basal forebrain and right hippocampal subfields showed that the B-SCD group had a larger Lambda than the G-SCD group, which suggested weakened network integration in the B-SCD group. At follow-up, the B-SCD group had a significantly higher conversion rate to MCI than the G-SCD group. Conclusion Compared to SCD participants with good spatial navigation performance, SCD participants with bad performance showed lower volumes in the basal forebrain, a reorganized structural covariance network of subcortical nuclei, and an increased risk of progression to MCI. Our findings indicated that spatial navigation may have great potential to identify SCD subjects at higher risk of clinical progression, which may contribute to making more precise clinical decisions for SCD individuals who seek medical help.

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Section: Discussionsupporting

confidence: 61%

Spatial navigation is associated with subcortical alterations and progression risk in subjective cognitive decline

Chen

Long

et al. 2023

Alz Res Therapy

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“…Recently, a causal SCN approach, i.e., causal relationships between morphometric features of different brain regions, has been proposed to better understand the underlying structural abnormalities related to AD progression, as it is likely that the atrophy in some brain regions has a causal influence on the atrophy of other regions (Zhang et al, 2017). In a recent study, causal SCN was evaluated in MCI and AD patients using the Granger causality analysis, and this study reported the atrophy in hippocampus, thalamus, and precuneus/posterior cingulate cortex had causal effects on the atrophy of other regions during AD progression (Qing et al, 2021). These findings demonstrate causal relationships among the brain atrophy in different regions related to the progression of AD.…”

Section: Introductionmentioning

confidence: 74%

Progressive structural and covariance connectivity abnormalities in patients with Alzheimer’s disease

Xiao

Wang²,

Huang³

et al. 2023

Front. Aging Neurosci.

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BackgroundAlzheimer’s disease (AD) is one of most prevalent neurodegenerative diseases worldwide and characterized by cognitive decline and brain structure atrophy. While studies have reported substantial grey matter atrophy related to progression of AD, it remains unclear about brain regions with progressive grey matter atrophy, covariance connectivity, and the associations with cognitive decline in AD patients.ObjectiveThis study aims to investigate the grey matter atrophy, structural covariance connectivity abnormalities, and the correlations between grey matter atrophy and cognitive decline during AD progression.MaterialsWe analyzed neuroimaging data of healthy controls (HC, n = 45) and AD patients (n = 40) at baseline (AD-T1) and one-year follow-up (AD-T2) obtained from the Alzheimer’s Disease Neuroimaging Initiative. We investigated AD-related progressive changes of grey matter volume, covariance connectivity, and the clinical relevance to further understand the pathological progression of AD.ResultsThe results showed clear patterns of grey matter atrophy in inferior frontal gyrus, prefrontal cortex, lateral temporal gyrus, posterior cingulate cortex, insula, hippocampus, caudate, and thalamus in AD patients. There was significant atrophy in bilateral superior temporal gyrus (STG) and left caudate in AD patients over a one-year period, and the grey matter volume decrease in right STG and left caudate was correlated with cognitive decline. Additionally, we found reduced structural covariance connectivity between right STG and left caudate in AD patients. Using AD-related grey matter atrophy as features, there was high discrimination accuracy of AD patients from HC, and AD patients at different time points.

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“…Decreased structural covariance pattern may indicate that structural association is weakened. It may be that neurodegeneration occurs in some regions and then spreads to other regions (Qing et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Percentage amplitude of fluctuation and structural covariance changes of subjective cognitive decline in patients: A multimodal imaging study

Wei¹,

Zhang²,

Zhao³

et al. 2022

Front. Neurosci.

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Back groundSubjective cognitive decline (SCD) may be the first clinical sign of Alzheimer’s disease (AD). The possible neural mechanisms of SCD are not well known. This study aimed to compare percent amplitude of fluctuation (PerAF) and structural covariance patterns in patients with SCD and healthy controls (HCs).MethodsWe enrolled 53 patients with SCD and 65 HCs. Resting-state functional magnetic resonance imaging (MRI) data and T1-weighted anatomical brain 3.0-T MRI scans were collected. The PerAF approach was applied to distinguish altered brain functions between the two groups. A whole-brain voxel-based morphometry analysis was performed, and all significant regions were selected as regions of interest (ROIs) for the structural covariance analysis. Statistical analysis was performed using two-sample t-tests, and multiple regressions were applied to examine the relationships between neuroimaging findings and clinical symptoms.ResultsFunctional MRI results revealed significantly increased PerAF including the right hippocampus (HIPP) and right thalamus (THA) in patients with SCD relative to HCs. Gray matter volume (GMV) results demonstrated decreased GMV in the bilateral ventrolateral prefrontal cortex (vlPFC) and right insula in patients with SCD relative to HCs. Taking these three areas including the bilateral vlPFC and right insula as ROIs, differences were observed in the structural covariance of the ROIs with several regions between the two groups. Additionally, significant correlations were observed between neuroimaging findings and clinical symptoms.ConclusionOur study investigated the abnormal PerAF and structural covariance patterns in patients with SCD, which might provide new insights into the pathological mechanisms of SCD.

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Causal structural covariance network revealing atrophy progression in Alzheimer's disease continuum

Cited by 19 publications

References 51 publications

Spatial navigation is associated with subcortical alterations and progression risk in subjective cognitive decline

Spatial navigation is associated with subcortical alterations and progression risk in subjective cognitive decline

Progressive structural and covariance connectivity abnormalities in patients with Alzheimer’s disease

Percentage amplitude of fluctuation and structural covariance changes of subjective cognitive decline in patients: A multimodal imaging study

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