| Title: |
Pathologic Substrates of Structural Brain Network Resilience and Topology in Parkinson Disease Decedents |
| Authors: |
Frigerio, I; Broeders, TAA; Lin, CP; Bouwman, MMA; Koubiyr, I; Barkhof, F; Berendse, HW; Van De Berg, WDJ; Douw, L; Jonkman, LE |
| Source: |
Neurology , 103 (4) , Article e209678. (2024) (In press). |
| Publisher Information: |
Ovid Technologies (Wolters Kluwer Health) |
| Publication Year: |
2024 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Humans; Parkinson Disease; Female; Male; Aged; 80 and over; Brain; alpha-Synuclein; Diffusion Magnetic Resonance Imaging; Nerve Net; Magnetic Resonance Imaging |
| Description: |
BACKGROUND AND OBJECTIVES: In Parkinson disease (PD), α-synuclein spreading through connected brain regions leads to neuronal loss and brain network disruptions. With diffusion-weighted imaging (DWI), it is possible to capture conventional measures of brain network organization and more advanced measures of brain network resilience. We aimed to investigate which neuropathologic processes contribute to regional network topologic changes and brain network resilience in PD. METHODS: Using a combined postmortem MRI and histopathology approach, PD and control brain donors with available postmortem in situ 3D T1-weighted MRI, DWI, and brain tissue were selected from the Netherlands Brain Bank and Normal Aging Brain Collection Amsterdam. Probabilistic tractography was performed, and conventional network topologic measures of regional eigenvector centrality and clustering coefficient, and brain network resilience (change in global efficiency upon regional node failure) were calculated. PSer129 α-synuclein, phosphorylated-tau, β-amyloid, neurofilament light-chain immunoreactivity, and synaptophysin density were quantified in 8 cortical regions. Group differences and correlations were assessed with rank-based nonparametric tests, with age, sex, and postmortem delay as covariates. RESULTS: Nineteen clinically defined and pathology-confirmed PD (7 F/12 M, 81 ± 7 years) and 15 control (8 F/7 M, 73 ± 9 years) donors were included. With regional conventional measures, we found lower eigenvector centrality only in the parahippocampal gyrus in PD (d = -1.08, 95% CI 0.003-0.010, p = 0.021), which did not associate with underlying pathology. No differences were found in regional clustering coefficient. With the more advanced measure of brain network resilience, we found that the PD brain network was less resilient to node failure of the dorsal anterior insula compared with the control brain network (d = -1.00, 95% CI 0.0012-0.0015, p = 0.018). This change was not directly driven by neuropathologic processes within the dorsal ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10195561/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10195561/3/Barkhof_frigerio-et-al-2024-pathologic-substrates-of-structural-brain-network-resilience-and-topology-in-parkinson-disease.pdf; https://discovery.ucl.ac.uk/id/eprint/10195561/ |
| Rights: |
open |
| Accession Number: |
edsbas.88D9A3B6 |
| Database: |
BASE |