APOE ε4 positivity predicts centrality of episodic memory nodes in patients with mild cognitive impairment: A cohort-based, graph theory-informed study of cognitive networks.

As network neuroscience can capture the systemic impact of APOE variability at a neuroimaging level, this study investigated the network-based cognitive endophenotypes of ε4-carriers and non-carriers across the continuum between normal ageing and Alzheimer's dementia (AD). We hypothesised that the impact of APOE-ε4 on cognitive functioning can be reliably captured by the measurement of graph-theory centrality. Cognitive networks were calculated in 8118 controls, 3482 MCI patients and 4573 AD patients, recruited in the National Alzheimer's Coordinating Center (NACC) database. Nodal centrality was selected as the neurofunctional readout of interest. ε4-carrier-vs.-non-carrier differences were tested in two independent NACC sub-cohorts assessed with either Version 1 or Version 2 of the Uniform Data Set neuropsychological battery. A significant APOE-dependent effect emerged from the analysis of the Logical-Memory nodes in MCI patients in both sub-cohorts. While non-carriers showed equal centrality in immediate and delayed recall, the latter was significantly less central among carriers (v1: bootstrapped confidence interval 0.107-0.667, p < 0.001; v2: bootstrapped confidence interval 0.018-0.432, p < 0.001). This indicates that, in carriers, delayed recall was, overall, significantly more weakly correlated with the other cognitive scores. These findings were replicated in the sub-groups of sole amnestic-MCI patients (n = 2971), were independent of differences in network communities, clinical severity or other demographic factors. No effects were found in the other two diagnostic groups. APOE-ε4 influences nodal properties of cognitive networks when patients are clinically classified as MCI. This highlights the importance of characterising the impact of risk factors on the wider cognitive network via network-neuroscience methodologies.

The influence of working memory and processing speed on other aspects of cognitive functioning in de novo Parkinson's disease: Initial findings from network modelling and graph theory.

Deficits in working memory (WM) and processing speed (PS) are thought to undermine other cognitive functions in de novo Parkinson's disease (dnPD). However, these interrelationships are only partially understood. This study investigated whether there are stronger relationships between verbal WM and verbal episodic memory encoding and retrieval, whether verbal WM and PS have a greater influence on other aspects of cognitive functioning, and whether the overall strength of interrelationships among several cognitive functions differs in dnPD compared to health. Data for 198 healthy controls (HCs) and 293 dnPD patients were analysed. Participants completed a neuropsychological battery probing verbal WM, PS, verbal episodic memory, semantic memory, language and visuospatial functioning. Deficit analysis, network modelling and graph theory were combined to compare the groups. Results suggested that verbal WM performance, while slightly impaired, was more strongly associated with measures of verbal episodic memory encoding and retrieval, as well as other measured cognitive functions in the dnPD network model compared to the HC network model. PS task performance was impaired and more strongly associated with other neuropsychological task scores in the dnPD model. Associations among task scores were stronger overall in the dnPD model. Together, these results provide further evidence that WM and PS are important influences on the other aspects of cognitive functioning measured in this study in dnPD. Moreover, they provide novel evidence that verbal WM and PS might bear greater influence on the other measured cognitive functions and that these functions are more strongly intertwined in dnPD compared to health.

Network neuropsychology: The map and the territory.

In "network neuropsychology", network modelling and graph theory is applied to the neuropsychological test scores of patients with neurological disorders to investigate cognitive functioning. This review identifies the emerging literature on several disorders before focusing on the assumptions about cognition underlying the studies; specifically, that cognition can be thought of as a network of interrelated variables and that changes in these interrelationships, or cognitive rearrangement, can occur in neurological disorders. Next the review appraises how well network models can provide a "map" of this cognitive "territory". In particular, the review considers the lack of correspondence between the variables and properties of network models and cognitive functioning. The challenges of explicitly accounting for latent cognitive constructs and making inferences about cognition based on associative, as opposed to dissociative, methods are also discussed. It is concluded that the validity of network neuropsychological models is yet to be established and that cognitive theory and experiments, as well as network models, are needed to develop and interpret better maps.