Poster No:
227
Submission Type:
Abstract Submission
Authors:
Tao Chen1, Rebekah Ahmed1, Olivier Piguet1, Muireann Irish1
Institutions:
1The University of Sydney, Sydney, New South Wales
First Author:
Tao Chen
The University of Sydney
Sydney, New South Wales
Co-Author(s):
Introduction:
The behavioural variant of frontotemporal dementia (bvFTD) is a younger-onset dementia syndrome characterised by early atrophy of frontoinsular cortices, manifesting in profound socioemotional and behavioural disturbances (Rascovsky et al., 2011). With disease progression, atrophy gradually progresses into anterior temporal and subcortical regions (Landin-Romero et al., 2017). Converging evidence from correlational, data-driven, and computational approaches indicates large-scale network-degeneration in bvFTD. While the insula is commonly implicated, it remains unclear whether insular atrophy causally impacts progressive large-scale structural network alterations in this population.
Methods:
To determine disease stage-specific grey matter atrophy in bvFTD, 82 patients were classified into very mild/mild (n=35), moderate (n=30), and severe (n=17) disease stage according to the FTLD-modified Clinical Dementia Rating (FTLD-CDR) scale (Miyagawa et al., 2020). Then, whole-brain voxel-based morphology (VBM) analysis was performed by CAT12 software to measure grey matter volume of all participants. Two-independent sample t-tests were used to compare grey matter volume between each bvFTD subgroup and corresponding healthy control groups matched for sex distribution, age, and education. These results were FDR-corrected at the voxel level (P < 0.005; k=300). To determine the potential causal effects of anterior insula on network-based atrophy in bvFTD, the grey matter maps of all bvFTD patients were ranked from low to high based on the FTLD-CDR sum of boxes score, supplemented by carer-rated behavioural changes on the Cambridge Behavioural Inventory. This enabled us to attribute "time-series" information to the cross-sectional structural imaging data. The left anterior insula was determined as the seed region, based on it being the most atrophied region in the overall bvFTD group (n=82) compared to controls (n=80). Using the REST software, the voxel-wise causal structural covariance network (CaSCN) was constructed to map anterior insula-driven structural network atrophy (Zhang et al., 2017). The CaSCN analysis was FDR-corrected at the voxel level (P < 0.01; k=300). Sex, age, education, total intracranial volume and scanning site were controlled as covariates in the above analyses. The difference between the FTLD-CDR scores across the neighbouring pseudo time points was additionally controlled for in the CaSCN analysis.
Results:
Patients in the very mild/mild disease burden stage showed predominant atrophy of frontotemporal (e.g., insula, temporal pole, middle frontal gyrus), limbic (e.g., hippocampus, amygdala), and subcortical (e.g., putamen, nucleus accumbens) brain areas. The moderate disease stage patients displayed widespread atrophy, extending to the middle cingulate, paracingulate gyri, and the thalamus, while the severe disease stage patients, extending from the frontotemporal and paracingulate/thalamic atrophy to more posterior brain regions, like the fusiform gyrus and Crus I of cerebellum. Importantly, our CaSCN analysis uncovered that grey matter atrophy progressively spreads from the left anterior insula to the dorsolateral prefrontal cortex, precuneus, lingual gyrus, posterior middle temporal gyrus, fusiform.
Conclusions:
Our findings suggest that atrophy of the anterior insula plays a central role in driving the progressive atrophy commonly seen in bvFTD, spreading to key regions in the executive control network and default mode network. The current study shed light into the network spread mechanism in terms of the causal influence of anterior insula atrophy on progressive brain atrophy in bvFTD.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Keywords:
Other - Insula, network degeneration, behavioral variant of frontotemporal dementia, causal network of structural covariance, disease progression
1|2Indicates the priority used for review
Provide references using author date format
Landin-Romero, R. (2017), “Disease-specific patterns of cortical and subcortical degeneration in a longitudinal study of Alzheimer's disease and behavioural-variant frontotemporal dementia”. NeuroImage, vol. 151, pp. 72-80
Miyagawa, T. (2020), “Utility of the global CDR® plus NACC FTLD rating and development of scoring rules: Data from the ARTFL/LEFFTDS Consortium”, Alzheimer's & dementia, vol. 16, no. 1, pp. 106-117
Rascovsky, K. (2011), “Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia”, Brain, vol. 134, no. 9, pp. 2456-2477
Zhang, Z. (2017), “Hippocampus-associated causal network of structural covariance measuring structural damage progression in temporal lobe epilepsy”, Human Brian Mapping, vol. 38, no. 2, pp. 753-766