scholarly journals From single layer to multilayer networks in Mild Cognitive Impairment and Alzheimer’s Disease

Author(s):  
Ignacio Echegoyen ◽  
David López-Sanz ◽  
Fernando Maestú ◽  
Javier M. Buldú

Abstract We investigate the alterations of functional networks of patients suffering from mild cognitive impairment (MCI) and Alzheimer’s disease (AD) when compared to healthy individuals. Departing from the magnetoencephalographic recordings of these three groups, we construct and analyse the corresponding single layer functional networks at different frequency bands, both at the sensors and the ROIs (regions of interest) levels. Different network parameters show statistically significant differences, with global efficiency being the one having the most pronounced differences between groups. Next, we extend the analyses to the frequency-band multilayer networks of the same dataset. Using the mutual information as a metric to evaluate the coordination between brain regions, we construct the αβ multilayer networks and analyse their algebraic connectivity at baseline λ2−BSL (i.e., the second smallest eigenvalue of the corresponding Laplacian matrices). We report statistically significant differences at the sensor level, despite the fact that these differences are not clearly observed when networks are obtained at the ROIs level (i.e., after a source reconstruction procedure). Next, we modify the weights of the inter-links of the multilayer network to identify the value of the algebraic connectivity λ2−T leading to a transition where layers can be considered to be fully merged. However, differences between the values of λ2−T of the three groups are not statistically significant. Finally, we developed nested multinomial logistic regression models (MNR models), with the aim of predicting group labels with the parameters extracted from the multilayer networks (λ2−BSL and λ2−T ). Using these models, we are able to quantify how age influences the risk of suffering AD and how the algebraic connectivity of frequency-based multilayer functional networks could be used as a biomarker of AD in clinical contexts.

2021 ◽  
Author(s):  
Noel Valencia ◽  
Johann Lehrner

Summary Background Visuo-Constructive functions have considerable potential for the early diagnosis and monitoring of disease progression in Alzheimer’s disease. Objectives Using the Vienna Visuo-Constructional Test 3.0 (VVT 3.0), we measured visuo-constructive functions in subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer’s disease (AD), and healthy controls to determine whether VVT performance can be used to distinguish these groups. Materials and methods Data of 671 participants was analyzed comparing scores across diagnostic groups and exploring associations with relevant clinical variables. Predictive validity was assessed using Receiver Operator Characteristic curves and multinomial logistic regression analysis. Results We found significant differences between AD and the other groups. Identification of cases suffering from visuo-constructive impairment was possible using VVT scores, but these did not permit classification into diagnostic subgroups. Conclusions In summary, VVT scores are useful indicators for visuo-constructive impairment but face challenges when attempting to discriminate between several diagnostic groups.


2020 ◽  
Author(s):  
Sang Won Seo ◽  
Seung Joo Kim ◽  
Sook-Young Woo ◽  
Young Ju Kim ◽  
Yeshin Kim ◽  
...  

Abstract Background: Few studies have investigated cognitive trajectories or developed a prediction model for amyloid beta-positive (Aβ+) mild cognitive impairment (MCI) patients. We aimed to identify distinct cognitive trajectories in Aβ+ MCI patients based on longitudinal Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-cog) 13 scores. Furthermore, we aimed to develop and visualize a prediction model to predict trajectory groups using the demographic, genetic, and clinical biomarkers of Aβ+ MCI patients.Methods: We performed a retrospective analysis of the data in 238 Aβ+ MCI patients from the Alzheimer’s Disease Neuroimaging Initiative who underwent at least three rounds of annual neuropsychological testing to identify cognitive trajectories. A group-based trajectory model (GBTM) was used to classify distinct groups based on ADAS-cog 13 scores. The prediction model was estimated using multinomial logistic regression and visualized using a bar-based method for risk prediction. Results: Three distinct classes, namely slow decliners (18.5%), intermediate decliners (42.9%), and fast decliners (38.7%), were suggested. Intermediate decliners were associated with higher age (≥70 years) (odds ratio [OR] 2.72, 95% confidence interval [CI] 1.78-6.28), higher AV45 standardized uptake value ratios (SUVRs)*10 (OR 1.69, 95% CI 1.22-2.34), and lower fluorodeoxyglucose (FDG) SUVR*10 (OR 0.65, 95% CI 0.46-0.93) than slow decliners. Fast decliners were associated with higher age (≥70 years) (OR 3.76, 95% CI 1.40-10.10), greater likelihood of being an apolipoprotein E 4 carrier (OR 4.2, 95% CI 1.53-11.58), higher AV45 positron emission tomography SUVR*10 (OR 2.14, 95% CI 1.50-3.05), and lower FDG SUVR*10 (OR 0.31, 95% CI 0.20-0.48) than slow decliners. The predicted probability of being classified to a trajectory group according to the risk scores of predictors was visualized.Conclusions: Our GBTM analysis yielded novel insights into the heterogeneous cognitive trajectories among Aβ+ MCI patients, which further facilitates the effective stratification of Aβ+ MCI patients in Aβ-targeted clinical trials.


2012 ◽  
Vol 110 (2) ◽  
pp. 477-488 ◽  
Author(s):  
Jonas Jardim de Paula ◽  
Lafaiete Moreira ◽  
Rodrigo Nicolato ◽  
Luiz Armando De Marco ◽  
Humberto Côrrea ◽  
...  

The Tower of London (TOL) is used for evaluating planning skills, which is a component of the executive functions. Different versions and scoring criteria were developed for this task, and some of them present with different psychometrical properties. This study aimed to evaluate two specific scoring methods of the TOL in diagnosing Mild Cognitive Impairment and probable Alzheimer's disease. The TOL total scores from 60 patients of each diagnosis were compared with the performance of 60 healthy-aged controls using receiver operating characteristics analysis and multinomial logistic regression. Krikorian method better diagnosed Alzheimer's disease, while Portellas's was better at discriminating healthy controls from Mild Cognitive Impairment, but were not efficient at comparing this last group with Alzheimer's patients. Regression analysis indicates that in addition to screening tests, TOL improves the classification of the three groups. The results suggest the two scoring methods used for this task may be useful for different diagnostic purposes.


2020 ◽  
Author(s):  
Ruaridh Clark ◽  
Niia Nikolova ◽  
William J. McGeown ◽  
Malcolm Macdonald

AbstractEigenvector alignment, introduced herein to investigate human brain functional networks, is adapted from methods developed to detect influential nodes and communities in networked systems. It is used to identify differences in the brain networks of subjects with Alzheimer’s disease (AD), amnestic Mild Cognitive Impairment (aMCI) and healthy controls (HC). Well-established methods exist for analysing connectivity networks composed of brain regions, including the widespread use of centrality metrics such as eigenvector centrality. However, these metrics provide only limited information on the relationship between regions, with this understanding often sought by comparing the strength of pairwise functional connectivity. Our holistic approach, eigenvector alignment, considers the impact of all functional connectivity changes before assessing the strength of the functional relationship, i.e. alignment, between any two regions. This is achieved by comparing the placement of regions in a Euclidean space defined by the network’s dominant eigenvectors. Eigenvector alignment recognises the strength of bilateral connectivity in cortical areas of healthy control subjects, but also reveals degradation of this commissural system in those with AD. Surprisingly little structural change is detected for key regions in the Default Mode Network, despite significant declines in the functional connectivity of these regions. In contrast, regions in the auditory cortex display significant alignment changes that begin in aMCI and are the most prominent structural changes for those with AD. Alignment differences between aMCI and AD subjects are detected, including notable changes to the hippocampal regions. These findings suggest eigenvector alignment can play a complementary role, alongside established network analytic approaches, to capture how the brain’s functional networks develop and adapt when challenged by disease processes such as AD.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
David Gamarra ◽  
Xabier Elcoroaristizabal ◽  
Manuel Fernández-Martínez ◽  
Marian M. de Pancorbo

Oxidative stress plays an important part in amnestic mild cognitive impairment (aMCI), the prodromal phase of Alzheimer’s disease (AD). Recent evidence shows that polymorphisms in theSOD2gene affect the elimination of the reactive oxygen species (ROS) generated in mitochondria. The aim of this study was to determine whether the functional rs4880 SNP in theSOD2gene is a risk factor associated with aMCI and sporadic AD. 216 subjects with aMCI, 355 with AD, and 245 controls have been studied. The SNP rs4880 of theSOD2gene was genotyped by RT-PCR and theAPOEgenotype was determined by PCR and RFLPs. Different multinomial logistic regression models were used to determine the risk levels for aMCI and AD. Although the T allele of the SOD2 rs4880 SNP gene (rs4880-T) is not an independent risk for aMCI or AD, this allele increases the risk to aMCI patients carrying at least one APOEε4 allele. Moreover, rs4880-T allele and APOEε4 allele combination has been found to produce an increased risk for AD compared to aMCI reference patients. These results suggest that APOEε4 and rs4880-T genotype may be a risk for aMCI and a predictor of progression from aMCI to AD.


PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e53922 ◽  
Author(s):  
Eun Hyun Seo ◽  
Dong Young Lee ◽  
Jong-Min Lee ◽  
Jun-Sung Park ◽  
Bo Kyung Sohn ◽  
...  

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