Abstract
Normative aging and Alzheimer’s disease (AD) propagation alter anatomical connections among brain parcels. However, the interaction between the trajectories of age- and AD-linked alterations in the topology of the structural brain network is not well understood. In this study, diffusion-weighted magnetic resonance imaging (MRI) datasets of 139 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were used to document their structural brain networks. The 139 participants consist of 45 normal controls (NCs), 37 with early mild cognitive impairment (EMCI), 27 with late mild cognitive impairment (LMCI), and 30 AD patients. All subjects were further divided into three subgroups based on their age (56–65, 66–75, and 71–85 years). After the structural connectivity networks were built using anatomically-constrained deterministic tractography, their global and nodal topological properties were estimated, including network efficiency, characteristic path length, transitivity, modularity coefficient, clustering coefficient, and betweenness. Statistical analyses were then performed on these metrics using linear regression, and one- and two-way ANOVA testing to examine group differences and interactions between aging and AD propagation. No significant interactions were found between aging and AD propagation in the global topological metrics (network efficiency, characteristic path length, transitivity, and modularity coefficient). However, nodal metrics (clustering coefficient and betweenness centrality) of some cortical parcels exhibited significant interactions between aging and AD propagation, with affected parcels including left superior temporal, right pars triangularis, and right precentral. The results collectively confirm the age-related deterioration of structural networks in MCI and AD patients, providing novel insight into the cross effects of aging and AD disorder on brain structural networks. Some early symptoms of AD may also be due to age-associated anatomic vulnerability interacting with early anatomic changes associated with AD.
Highlights
Increasing evidence suggests that both aging and Alzheimer’s disease (AD) can cause deterioration in anatomical brain connections, which is associated with a decline in cognitive abilities (Peters, 2002; Perl, 2010; Teipel et al, 2016)
The primary goal of Alzheimer’s Disease Neuroimaging Initiative (ADNI) has been to test whether magnetic resonance imaging (MRI), positron emission tomography (PET), biomarkers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early AD (Jack et al, 2008; Risacher et al, 2009; Petersen et al, 2010)
Linear regression was performed on the global topological metrics to examine whether, over age, the structural networks of MCI and AD patients exhibited similar deterioration patterns
Summary
Increasing evidence suggests that both aging and Alzheimer’s disease (AD) can cause deterioration in anatomical brain connections, which is associated with a decline in cognitive abilities (Peters, 2002; Perl, 2010; Teipel et al, 2016). As a neurodegenerative disorder that reduces synaptic transmission (Morabito et al, 2015), AD causes a gradual breakdown in brain structural connectivity, eventually resulting in dementia (Voevodskaya et al, 2018; Dai et al, 2019; Wu et al, 2019). This disruption of structural connectivity between key functional subregions may explain the characteristic deficits found in AD patients (Yao et al, 2010; Fischer et al, 2015; delEtoile and Adeli, 2017; Li et al, 2020). These age- and AD-related alterations in white matter organization can profoundly affect topological features of the brain structural network and synergistically damage its integrity (Palop et al, 2006)
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