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Lookup NU author(s): Dr Laura WrightORCiD, Dr Paul DonaghyORCiD, Professor David BurnORCiD, Professor John-Paul TaylorORCiD, Professor Alison YarnallORCiD, Professor Fiona MatthewsORCiD, Dr Michael FirbankORCiD, Dr Hilmar SigurdssonORCiD, Julia SchumacherORCiD, Professor Alan ThomasORCiD, Dr Rachael LawsonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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 (MCILB, 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
Author(s): Wright LM, Donaghy PC, Burn DJ, Taylor J-P, OBrien JT, Yarnall AJ, Matthews FE, Firbank MJ, Sigurdsson HP, Schumacher J, Thomas AJ, Lawson RA
Publication type: Article
Publication status: Published
Journal: Neurobiology of Aging
Year: 2025
Volume: 151
Pages: 95-106
Print publication date: 01/07/2025
Online publication date: 17/04/2025
Acceptance date: 16/04/2025
Date deposited: 17/04/2025
ISSN (print): 0197-4580
ISSN (electronic): 1558-1497
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.neurobiolaging.2025.04.007
DOI: 10.1016/j.neurobiolaging.2025.04.007
ePrints DOI: 10.57711/zzxy-sb13
Data Access Statement: Data are available upon reasonable request.
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