Abstract
BackgroundStructural network alterations in Alzheimer’s disease (AD) are related to worse cognitive impairment. The aim of this study was to quantify the alterations in gray matter associated with impaired cognition and their pathological biomarkers in AD-spectrum patients.MethodsWe extracted gray matter networks from 3D-T1 magnetic resonance imaging scans, and a graph theory analysis was used to explore alterations in the network metrics in 34 healthy controls, 70 mild cognitive impairment (MCI) patients, and 40 AD patients. Spearman correlation analysis was computed to investigate the relationships among network properties, neuropsychological performance, and cerebrospinal fluid pathological biomarkers (i.e., Aβ, t-tau, and p-tau) in these subjects.ResultsAD-spectrum individuals demonstrated higher nodal properties and edge properties associated with impaired memory function, and lower amyloid-β or higher tau levels than the controls. Furthermore, these compensations at the brain regional level in AD-spectrum patients were mainly in the medial temporal lobe; however, the compensation at the whole-brain network level gradually extended from the frontal lobe to become widely distributed throughout the cortex with the progression of AD.ConclusionThe findings provide insight into the alterations in the gray matter network related to impaired cognition and pathological biomarkers in the progression of AD. The possibility of compensation was detected in the structural networks in AD-spectrum patients; the compensatory patterns at regional and whole-brain levels were different and the clinical significance was highlighted.
Highlights
Alzheimer’s disease (AD), the most prevalent cause of dementia, is characterized by progressive loss in the activities of daily living and cognitive impairment, which causes a very large socioeconomic burden (van der Lee et al, 2018)
Multiple cognitive functions were more impaired in mild cognitive impairment (MCI) and AD patients than in the controls, and the largest differences were between AD patients and the
No significant correlation was calculated between altered nodal properties and cerebrospinal fluid (CSF) biomarkers in healthy controls (HC) and MCI patients, and the betweenness centrality in the right parahippocampal gyrus was negatively correlated with CSF t-tau (r =-0.373, P = 0.03) (Figure 4A) and p-tau (r = -0.386, P = 0.024) (Figure 4B) concentration in AD patients
Summary
Alzheimer’s disease (AD), the most prevalent cause of dementia, is characterized by progressive loss in the activities of daily living and cognitive impairment, which causes a very large socioeconomic burden (van der Lee et al, 2018). Previous studies have shown that changes in structural properties in gray matter are related to the degree of cognitive impairment and disease severity in individuals with AD (Vipin et al, 2018). Structural similarity within the gray matter network in individuals with cognitive impairment was mainly related to the thalamus, insula, and occipital cortex and was associated with poor memory performance (Ahmed et al, 2019). There has been no research exploring the altered structural network measures related to pathological biomarkers in combination with the structural similarity and topological properties in patients with cognitive impairment. The aim of this study was to quantify the alterations in gray matter associated with impaired cognition and their pathological biomarkers in AD-spectrum patients
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