Network Disruption in the Preclinical Stages of Alzheimer’s Disease: From Subjective Cognitive Decline to Mild Cognitive Impairment

López‐Sanz, David; Garcés, Pilar; Álvarez, Blanca; Delgado-Losada, María Luisa; López-Higes, Ramón; Maestú, Fernando

doi:10.1142/s0129065717500411

Cited by 66 publications

(45 citation statements)

References 100 publications

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“…Then, disruption of network efficiency can be directly explained by propagated amyloid pathology across the brain region of AD subjects. On the other hand, the increases in modularity for [ 18 F]FDG-PET, accentuated after PVEc, match commonly reported findings from structural and functional MRI network studies into the neurodegenerative side of AD (Lopez-Sanz et al 2017;Pereira et al 2016). The results are in line with recent studies highlighting the relevance of studying networks derived from [ 18 F]FDG-PET in AD (Veronese et al 2019).…”

Section: Impact Of Pvec On Network Modularity Local and Global Efficsupporting

confidence: 90%

Metabolic and amyloid PET network reorganization in Alzheimer’s disease: differential patterns and partial volume effects

González‐Escamilla

Miederer²,

Grothe

et al. 2020

Brain Imaging and Behavior

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Alzheimer's disease (AD) is a neurodegenerative disorder, considered a disconnection syndrome with regional molecular pattern abnormalities quantifiable by the aid of PET imaging. Solutions for accurate quantification of network dysfunction are scarce. We evaluate the extent to which PET molecular markers reflect quantifiable network metrics derived through the graph theory framework and how partial volume effects (PVE)-correction (PVEc) affects these PET-derived metrics 75 AD patients and 126 cognitively normal older subjects (CN). Therefore our goal is twofold: 1) to evaluate the differential patterns of [ 18 F]FDG-and [ 18 F]AV45-PET data to depict AD pathology; and ii) to analyse the effects of PVEc on global uptake measures of [ 18 F]FDG-and [ 18 F]AV45-PET data and their derived covariance network reconstructions for differentiating between patients and normal older subjects. Network organization patterns were assessed using graph theory in terms of "degree", "modularity", and "efficiency". PVEc evidenced effects on global uptake measures that are specific to either [ 18 F]FDG-or [ 18 F]AV45-PET, leading to increased statistical differences between the groups. PVEc was further shown to influence the topological characterization of PET-derived covariance brain networks, leading to an optimised characterization of network efficiency and modularisation. Partial-volume effects correction improves the interpretability of PET data in AD and leads to optimised characterization of network properties for organisation or disconnection.

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Section: Impact Of Pvec On Network Modularity Local and Global Efficsupporting

confidence: 90%

Metabolic and amyloid PET network reorganization in Alzheimer’s disease: differential patterns and partial volume effects

González‐Escamilla

Miederer²,

Grothe

et al. 2020

Brain Imaging and Behavior

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“…Multifaceted patterns of increased and decreased connectivity between regions could reflect breakdown in processing within a subnetwork that shifts processing load to more intact components of the broader network. Diffuse and frontally localized MEG alpha band power reductions have also been noted in older adults with SCD [39,46], without group differences in the small world properties of theta and beta bands [58]. Moreover, lower subgraph centrality (a measure of weighted, closed walks starting and ending at a node, representing mid-scale connectivity) has been observed in occipital and paracentral regions in older adults with SCD [48].…”

Section: Brain Network Functional Connectivity In Subjective Cognitivmentioning

confidence: 93%

Functional neuroimaging in subjective cognitive decline: current status and a research path forward

Viviano

Damoiseaux

2020

Alz Res Therapy

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Subjective cognitive decline is a putative precursor to dementia marked by perceived worsening of cognitive function without overt performance issues on neuropsychological assessment. Although healthy older adults with subjective cognitive decline may function normally, perceived worsening may indicate incipient dementia and predict future deterioration. Therefore, the experience of decline represents a possible entry point for clinical intervention. However, intervention requires a physical manifestation of neuroabnormality to both corroborate incipient dementia and to target clinically. While some individuals with subjective cognitive decline may harbor pathophysiology for specific neurodegenerative disorders, many do not display clear indicators. Thus, disorder-agnostic brain measures could be useful to track the trajectory of decline, and functional neuroimaging in particular may be sensitive to detect incipient dementia and have the ability to track disease-related change when the underlying disease etiology remains unclear. Therefore, in this review, we discuss functional neuroimaging studies of subjective cognitive decline and possible reconciliations to inconsistent findings. We conclude by proposing a functional model where noisy signal propagation and inefficient signal processing across whole-brain networks may lead to the subjective experience of decline and discuss future research directions guided by this model.

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“…Artifact-free data were segmented in 4 seconds epochs. Then MEG time series were filtered into delta (2-4Hz), theta (4-8Hz), alpha (8-12Hz) and beta (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). This procedure has been reported in detailed in (22).…”

Section: Magnetoencephalographymentioning

confidence: 99%

“…Early loss of inhibitory neurons in preclinical AD leads to a state of increased hyperexcitability and hypersynchrony (13)(14)(15), which has been found to augment amyloid release and produce neurotoxic effects (16,17). We hypothesize that PA exerts a neuroprotective effect that will be associated with reduced network synchrony in both groups, in opposition to the state of synaptic hyperexcitability that characterizes preclinical and prodromal AD (18)(19)(20)(21)(22). Then, once we have identified the functional connectivity (FC) patterns that are influenced by PA level, we will explore if there are any associations between these FC patterns and structural integrity (grey and white matter), cognition, and mood.…”

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confidence: 99%

The relationship between physical activity, apolipoprotein E ε4 carriage and brain health

Frutos-Lucas

Cuesta

López‐Sanz

et al. 2020

Preprint

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BACKGROUND: Neuronal hyperexcitability and hypersynchrony have been described as key features of neurophysiological dysfunctions in the Alzheimer’s disease (AD) continuum. Conversely, physical activity (PA) has been associated with improved brain health and reduced AD risk. However, there is controversy regarding whether AD genetic risk (in terms of APOE ε4 carriage) modulates these relationships. The utilization of multiple outcome measures within one sample may strengthen our understanding of this complex phenomenon. METHOD: The relationship between PA and functional connectivity (FC) was examined in a sample of 107 healthy older adults using magnetoencephalography. Additionally, we explored whether ε4 carriage modulates this association. The correlation between FC and brain structural integrity, cognition and mood was also investigated. RESULTS: A relationship between higher PA and decreased FC (hyposynchrony) in the left temporal lobe was observed among all individuals (across the whole sample, in ε4 carriers and in ε4 non-carriers), but its effects manifest differently according to genetic risk. In ε4 carriers, we report an association between this region-specific FC profile and preserved brain structure (greater gray matter volumes and higher integrity of white matter tracts). In this group decreased FC also correlated with reduced anxiety levels. In ε4 non-carriers, this profile is associated with improved cognition (working and episodic memory). CONCLUSIONS: PA could mitigate the increase in FC (hypersynchronization) that characterizes preclinical AD, being beneficial for all individuals, specially ε4 carriers.

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Network Disruption in the Preclinical Stages of Alzheimer’s Disease: From Subjective Cognitive Decline to Mild Cognitive Impairment

Cited by 66 publications

References 100 publications

Metabolic and amyloid PET network reorganization in Alzheimer’s disease: differential patterns and partial volume effects

Metabolic and amyloid PET network reorganization in Alzheimer’s disease: differential patterns and partial volume effects

Functional neuroimaging in subjective cognitive decline: current status and a research path forward

The relationship between physical activity, apolipoprotein E ε4 carriage and brain health

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