CT-based volumetric measures obtained through deep learning: Association with biomarkers of neurodegeneration published on Alzheimer’s & Dementia

Imaging-based volumetric measures. (Image by the Authors of the manuscript.)
CT-based volumetric measures obtained through deep learning: Association with biomarkers of neurodegeneration
Meera Srikrishna, Nicholas J. Ashton, Alexis Moscoso, Joana B. Pereira, Rolf A. Heckemann, Danielle van Westen, Giovanni Volpe, Joel Simrén, Anna Zettergren, Silke Kern, Lars-Olof Wahlund, Bibek Gyanwali, Saima Hilal, Joyce Chong Ruifen, Henrik Zetterberg, Kaj Blennow, Eric Westman, Christopher Chen, Ingmar Skoog, Michael Schöll
Alzheimer’s & Dementia 20, 629–640 (2024)
arXiv: 2401.06260
doi: 10.1002/alz.13445

INTRODUCTION
Cranial computed tomography (CT) is an affordable and widely available imaging modality that is used to assess structural abnormalities, but not to quantify neurodegeneration. Previously we developed a deep-learning–based model that produced accurate and robust cranial CT tissue classification.

MATERIALS AND METHODS
We analyzed 917 CT and 744 magnetic resonance (MR) scans from the Gothenburg H70 Birth Cohort, and 204 CT and 241 MR scans from participants of the Memory Clinic Cohort, Singapore. We tested associations between six CT-based volumetric measures (CTVMs) and existing clinical diagnoses, fluid and imaging biomarkers, and measures of cognition.

RESULTS
CTVMs differentiated cognitively healthy individuals from dementia and prodromal dementia patients with high accuracy levels comparable to MR-based measures. CTVMs were significantly associated with measures of cognition and biochemical markers of neurodegeneration.

DISCUSSION
These findings suggest the potential future use of CT-based volumetric measures as an informative first-line examination tool for neurodegenerative disease diagnostics after further validation.

Multi-cohort and longitudinal Bayesian clustering study of stage and subtype in Alzheimer’s disease published in Nature Communications

Comparison of cluster-specific covariance matrixes with node strength. (Image by the Authors.)
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)
doi: 10.1038/s41467-022-32202-6

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 Alzheimer published in Cerebral Cortex

Disrupted Network Topology in Patients with Stable and Progressive Mild Cognitive Impairment and Alzheimer’s Disease

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

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.