Laura M Wright
Brain network connectivity underlying neuropsychiatric symptoms in prodromal Lewy body dementia
Wright, Laura M; Donaghy, Paul C; Burn, David J; Taylor, John-Paul; O'OBrien, John T; Yarnall, Alison J; Matthews, Fiona E; Firbank, Michael J; Sigurdsson, Hilmar P; Schumacher, Julia; Thomas, Alan J; Lawson, Rachael A
Authors
Paul C Donaghy
David J Burn
John-Paul Taylor
John T O'OBrien
Alison J Yarnall
Professor Fiona Matthews F.Matthews@hull.ac.uk
Pro-Vice-Chancellor Research and Enterprise
Michael J Firbank
Hilmar P Sigurdsson
Julia Schumacher
Alan J Thomas
Rachael A Lawson
Abstract
Neuropsychiatric symptoms (NPS) are prevalent, emerge early, and are associated with poorer outcomes in Lewy body dementia (LBD). Research suggests NPS may reflect LBD-related dysfunction in distributed neuronal networks. This study investigated NPS neural correlates in prodromal LBD using resting-state functional MRI.
Fifty-seven participants were included with mild cognitive impairment (MCI) with Lewy bodies (MCI-LB, n=28) or Parkinson’s disease (PD-MCI, n=29). Functional MRI assessed connectivity within five resting-state networks: primary visual, dorsal attention, salience, limbic, and default mode networks. NPS were measured using the Neuropsychiatric Inventory. Principal component analyses identified three neuropsychiatric factors: affective disorder (apathy, depression), psychosis (delusions, hallucinations) and anxiety. Seed-to-voxel connectivity maps were analysed to determine associations between NPS and network connectivity.
In PD-MCI, affective symptoms and anxiety were associated with greater connectivity between limbic orbitofrontal cortex and default mode areas, including medial prefrontal cortex, subgenual cingulate and precuneus, and weaker connectivity between limbic orbitofrontal cortex and the brainstem and between the salience network and medial prefrontal cortex (all pFWE<0.001). Psychosis severity in PD-MCI correlated with connectivity across multiple networks (all pFWE<0.001). In MCI-LB, no significant correlations were found between NPS severity and network connectivity. However, participants with anxiety demonstrated a trend towards greater connectivity within medial prefrontal areas than those without (pFWE=0.046).
Altered connectivity within and between networks associated with mood disorders may explain affective and anxiety symptoms in PD-MCI. Neural correlates of NPS in MCI-LB, however, remain unclear, highlighting the need for research in larger, more diverse LBD populations to identify symptomatic treatment targets.
Citation
Wright, L. M., Donaghy, P. C., Burn, D. J., Taylor, J.-P., O'OBrien, J. T., Yarnall, A. J., Matthews, F. E., Firbank, M. J., Sigurdsson, H. P., Schumacher, J., Thomas, A. J., & Lawson, R. A. (in press). Brain network connectivity underlying neuropsychiatric symptoms in prodromal Lewy body dementia. Neurobiology of Aging, https://doi.org/10.1016/j.neurobiolaging.2025.04.007
| Journal Article Type | Article |
|---|---|
| Acceptance Date | Apr 16, 2025 |
| Online Publication Date | Apr 17, 2025 |
| Deposit Date | Apr 17, 2025 |
| Publicly Available Date | Apr 18, 2026 |
| Print ISSN | 0197-4580 |
| Publisher | Elsevier |
| Peer Reviewed | Peer Reviewed |
| DOI | https://doi.org/10.1016/j.neurobiolaging.2025.04.007 |
| Keywords | Parkinson’s disease; Dementia with Lewy bodies; Neuroimaging; Neuropsychiatry; Mild cognitive impairment; fMRI; Resting-state networks |
| Public URL | https://hull-repository.worktribe.com/output/5131252 |
Files
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