Multi-cohort and longitudinal Bayesian clustering study of stage and subtype in Alzheimer’s disease
Konstantinos Poulakis, Joana B. Pereira, J.-Sebastian Muehlboeck, Lars-Olof Wahlund, Örjan Smedby, Giovanni Volpe, Colin L. Masters, David Ames, Yoshiki Niimi, Takeshi Iwatsubo, Daniel Ferreira, Eric Westman, Japanese Alzheimer’s Disease Neuroimaging Initiative & Australian Imaging, Biomarkers and Lifestyle study
Nature Communications 13, 4566 (2022)
Understanding Alzheimer’s disease (AD) heterogeneity is important for understanding the underlying pathophysiological mechanisms of AD. However, AD atrophy subtypes may reflect different disease stages or biologically distinct subtypes. Here we use longitudinal magnetic resonance imaging data (891 participants with AD dementia, 305 healthy control participants) from four international cohorts, and longitudinal clustering to estimate differential atrophy trajectories from the age of clinical disease onset. Our findings (in amyloid-β positive AD patients) show five distinct longitudinal patterns of atrophy with different demographical and cognitive characteristics. Some previously reported atrophy subtypes may reflect disease stages rather than distinct subtypes. The heterogeneity in atrophy rates and cognitive decline within the five longitudinal atrophy patterns, potentially expresses a complex combination of protective/risk factors and concomitant non-AD pathologies. By alternating between the cross-sectional and longitudinal understanding of AD subtypes these analyses may allow better understanding of disease heterogeneity.
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)
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 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)
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.