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Brain network connectivity underlying neuropsychiatric symptoms in prodromal Lewy body dementia
Laura Wright, Paul C. Donaghy, David John Burn, John‐Paul Taylor, John Tiernan O'Brien, Alison Jane Yarnall, Fiona E. Matthews, Michael John Firbank et al.. Neurobiology of Aging, 2025-04-17
Topic: Brain proteins, microglia and lab models
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.
Key findings
- Neuropsychiatric symptoms (NPS) are prevalent, emerge early, and are associated with poorer outcomes in Lewy body dementia (LBD).
- 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).
- 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.
Why it matters
In this small study of 57 participants, no significant correlations were found between neuropsychiatric symptom severity and network connectivity in MCI with Lewy bodies. In Parkinson's disease MCI, affective symptoms, anxiety and psychosis were linked to patterns of brain network connectivity, but this does not establish a treatment or cure.
Study details
- Participants28
- Evidence strengthLow
How this study scored 44/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of Aging) |
| Journal's citation record | 3 / 4 | Neurobiology of Aging: journal h-index 263 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 28 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Rachael Ashleigh Lawson: h-index 33 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40267731) |
| Free to read | 2 / 2 | Free to read |
| Total | 44 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.neurobiolaging.2025.04.007
- PubMed: 40267731
- Original source →
- Free full text: Neurobiology of Aging →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Wright, L., Donaghy, P. C., Burn, D. J., Taylor, J., O'Brien, J. T., Yarnall, A. J., et al. (2025). Brain network connectivity underlying neuropsychiatric symptoms in prodromal Lewy body dementia. Neurobiology of Aging. https://doi.org/10.1016/j.neurobiolaging.2025.04.007
Vancouver
Wright L, Donaghy PC, Burn DJ, Taylor J, O'Brien JT, Yarnall AJ, et al. Brain network connectivity underlying neuropsychiatric symptoms in prodromal Lewy body dementia. Neurobiology of Aging. 2025. doi:10.1016/j.neurobiolaging.2025.04.007. PMID: 40267731.
BibTeX
@article{wright2025-40267731,
author = {Wright, Laura and Donaghy, Paul C. and Burn, David John and Taylor, John‐Paul and O'Brien, John Tiernan and Yarnall, Alison Jane and Matthews, Fiona E. and Firbank, Michael John and others},
title = {{Brain network connectivity underlying neuropsychiatric symptoms in prodromal Lewy body dementia}},
journal = {Neurobiology of Aging},
year = {2025},
doi = {10.1016/j.neurobiolaging.2025.04.007},
pmid = {40267731},
url = {https://doi.org/10.1016/j.neurobiolaging.2025.04.007}
}
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