Joana B. Pereira – Page 3 – Soft Matter Lab

Amyloid Network Topology in Alzheimer published in Cerebral Cortex

Amyloid network topology characterizes the progression of Alzheimer’s disease during the predementia stages
Joana B. Pereira, Tor Olof Strandberg, Sebastian Palmqvist, Giovanni Volpe, Danielle van Westen, Eric Westman & Oskar Hansson, for the Alzheimer’s Disease Neuroimaging Initiative
Cerebral Cortex 28(1), 340—349 (2018)
DOI: 10.1093/cercor/bhx294

There is increasing evidence showing that the accumulation of the amyloid-β (Aβ) peptide into extracellular plaques is a central event in Alzheimer’s disease (AD). These abnormalities can be detected as lowered levels of Aβ42 in the cerebrospinal fluid (CSF) and are followed by increased amyloid burden on positron emission tomography (PET) several years before the onset of dementia. The aim of this study was to assess amyloid network topology in nondemented individuals with early stage Aβ accumulation, defined as abnormal CSF Aβ42 levels and normal Florbetapir PET (CSF+/PET−), and more advanced Aβ accumulation, defined as both abnormal CSF Aβ42 and Florbetapir PET (CSF+/PET+). The amyloid networks were built using correlations in the mean 18F-florbetapir PET values between 72 brain regions and analyzed using graph theory analyses. Our findings showed an association between early amyloid stages and increased covariance as well as shorter paths between several brain areas that overlapped with the default-mode network (DMN). Moreover, we found that individuals with more advanced amyloid accumulation showed more widespread changes in brain regions both within and outside the DMN. These findings suggest that amyloid network topology could potentially be used to assess disease progression in the predementia stages of AD.

Abnormal Structural Brain Connectome in Preclinical Alzheimer published in Cerebral Cortex

Abnormal structural brain connectome in individuals with preclinical Alzheimer’s disease
Joana B. Pereira, Danielle van Westen, Erik Stomrud, Tor Olof Strandberg, Giovanni Volpe, Eric Westman & Oskar Hansson
Cerebral Cortex 28(10), 3638—3649 (2018)
DOI: 10.1093/cercor/bhx236

Alzheimer’s disease has a long preclinical phase during which amyloid pathology and neurodegeneration accumulate in the brain without producing overt cognitive deficits. It is currently unclear whether these early disease stages are associated with a progressive disruption in the communication between brain regions that subsequently leads to cognitive decline and dementia. In this study we assessed the organization of structural networks in cognitively normal (CN) individuals harboring amyloid pathology (A+N−), neurodegeneration (A−N+), or both (A+N+) from the prospective and longitudinal Swedish BioFINDER study. We combined graph theory with diffusion tensor imaging to investigate integration, segregation, and centrality measures in the brain connectome in the previous groups. At baseline, our findings revealed a disrupted network topology characterized by longer paths, lower efficiency, increased clustering and modularity in CN A−N+ and CN A+N+, but not in CN A+N−. After 2 years, CN A+N+ showed significant abnormalities in all global network measures, whereas CN A−N+ only showed abnormalities in the global efficiency. Network connectivity and organization were associated with memory in CN A+N+ individuals. Altogether, our findings suggest that amyloid pathology is not sufficient to disrupt structural network topology, whereas neurodegeneration is.

Featured in “Nuke med helps diagnose early Alzheimer’s from amyloid network topology”, HealthImaging, 14 Nov 2017

BRAPH published in Plos ONE

BRAPH: A graph theory software for the analysis of brain connectivity
Mite Mijalkov, Ehsan Kakaei, Joana B. Pereira, Eric Westman & Giovanni Volpe
PLoS ONE 12(8), e0178798 (2017)
DOI: 10.1371/journal.pone.0178798
bioRxiv: 106625

The brain is a large-scale complex network whose workings rely on the interaction between its various regions. In the past few years, the organization of the human brain network has been studied extensively using concepts from graph theory, where the brain is represented as a set of nodes connected by edges. This representation of the brain as a connectome can be used to assess important measures that reflect its topological architecture. We have developed a freeware MatLab-based software (BRAPH–BRain Analysis using graPH theory) for connectivity analysis of brain networks derived from structural magnetic resonance imaging (MRI), functional MRI (fMRI), positron emission tomography (PET) and electroencephalogram (EEG) data. BRAPH allows building connectivity matrices, calculating global and local network measures, performing non-parametric permutations for group comparisons, assessing the modules in the network, and comparing the results to random networks. By contrast to other toolboxes, it allows performing longitudinal comparisons of the same patients across different points in time. Furthermore, even though a user-friendly interface is provided, the architecture of the program is modular (object-oriented) so that it can be easily expanded and customized. To demonstrate the abilities of BRAPH, we performed structural and functional graph theory analyses in two separate studies. In the first study, using MRI data, we assessed the differences in global and nodal network topology in healthy controls, patients with amnestic mild cognitive impairment, and patients with Alzheimer’s disease. In the second study, using resting-state fMRI data, we compared healthy controls and Parkin- son’s patients with mild cognitive impairment.

Disrupted Network Topology in Alzheimer published in Cerebral Cortex

Disrupted Network Topology in Patients with Stable and Progressive Mild Cognitive Impairment and Alzheimer’s Disease
Joana B. Pereira, Mite Mijalkov, Ehsan Kakaei, Patricia Mecocci, Bruno Vellas, Magda Tsolaki, Iwona Kłoszewska, Hilka Soininen, Christian Spenger, Simmon Lovestone, Andrew Simmons, Lars-Olof Wahlund, Giovanni Volpe & Eric Westman, AddNeuroMed consortium, for the Alzheimer’s Disease Neuroimaging Initiative
Cerebral Cortex 26(8), 3476—3493 (2016)
DOI: 10.1093/cercor/bhw128

Recent findings suggest that Alzheimer’s disease (AD) is a disconnection syndrome characterized by abnormalities in large- scale networks. However, the alterations that occur in network topology during the prodromal stages of AD, particularly in patients with stable mild cognitive impairment (MCI) and those that show a slow or faster progression to dementia, are still poorly understood. In this study, we used graph theory to assess the organization of structural MRI networks in stable MCI (sMCI) subjects, late MCI converters (lMCIc), early MCI converters (eMCIc), and AD patients from 2 large multicenter cohorts: ADNI and AddNeuroMed. Our findings showed an abnormal global network organization in all patient groups, as reflected by an increased path length, reduced transitivity, and increased modularity compared with controls. In addition, lMCIc, eMCIc, and AD patients showed a decreased path length and mean clustering compared with the sMCI group. At the local level, there were nodal clustering decreases mostly in AD patients, while the nodal closeness centrality detected abnormalities across all patient groups, showing overlapping changes in the hippocampi and amygdala and nonoverlapping changes in parietal, entorhinal, and orbitofrontal regions. These findings suggest that the prodromal and clinical stages of AD are associated with an abnormal network topology.

Aberrant Cerebral Topology in Early Parkinson published in Human Brain Mapp.

Aberrant cerebral network topology and mild cognitive impairment in early Parkinson’s disease
Joana B. Pereira, Dag Aarsland, Cedric E. Ginestet, Alexander V. Lebedev, Lars-Olof Wahlund, Andrew Simmons, Giovanni Volpe & Eric Westman
Human Brain Mapping 36(8), 2980—2995 (2015)
DOI: 10.1002/hbm.22822

The aim of this study was to assess whether mild cognitive impairment (MCI) is associated with disruption in large-scale structural networks in newly diagnosed, drug-na€ıve patients with Parkin- son’s disease (PD). Graph theoretical analyses were applied to 3T MRI data from 123 PD patients and 56 controls from the Parkinson’s progression markers initiative (PPMI). Thirty-three patients were classified as having Parkinson’s disease with mild cognitive impairment (PD-MCI) using the Movement Disorders Society Task Force criteria, while the remaining 90 PD patients were classified as cognitively normal (PD- CN). Global measures (clustering coefficient, characteristic path length, global efficiency, small-world- ness) and regional measures (regional clustering coefficient, regional efficiency, hubs) were assessed in the structural networks that were constructed based on cortical thickness and subcortical volume data. PD-MCI patients showed a marked reduction in the average correlation strength between cortical and subcortical regions compared with controls. These patients had a larger characteristic path length and reduced global efficiency in addition to a lower regional efficiency in frontal and parietal regions com- pared with PD-CN patients and controls. A reorganization of the highly connected regions in the network was observed in both groups of patients. This study shows that the earliest stages of cognitive decline in PD are associated with a disruption in the large-scale coordination of the brain network and with a decrease of the efficiency of parallel information processing. These changes are likely to signal further cognitive decline and provide support to the role of aberrant network topology in cognitive impairment in patients with early PD.