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Neuroinflammation is independently associated with brain network dysfunction in Alzheimer's disease
Leng F, Hinz R, Gentleman S, Hampshire A, Dani M, Brooks DJ, Edison P.. Molecular psychiatry, 2022-12-06
Topic: Amyloid, tau and blood-test diagnosis
Brain network dysfunction is increasingly recognised in Alzheimer's disease (AD). However, the causes of brain connectivity disruption are still poorly understood. Recently, neuroinflammation has been identified as an important factor in AD pathogenesis. Microglia participate in the construction and maintenance of healthy neuronal networks, but pro-inflammatory microglia can also damage these circuits. We hypothesised that microglial activation is independently associated with brain connectivity disruption in AD. We performed a cross-sectional multimodal imaging study and interrogated the relationship between imaging biomarkers of neuroinflammation, Aβ deposition, brain connectivity and cognition. 42 participants (12 Aβ-positive MCI, 14 Aβ-positive AD and 16 Aβ-negative healthy controls) were recruited. Participants had 11 C-PBR28 and 18 F-flutemetamol PET to quantify Aβ deposition and microglial activation, T1-weighted, diffusion tensor and resting-state functional MRI to assess structural network and functional network. 11 C-PBR28 uptake, structural network integrity and functional network orgnisation were compared across diagnostic groups and the relationship between neuroinflammation and brain network was tested in 26 Aβ-positive patients. Increased 11 C-PBR28 uptake, decreased FA, network small-worldness and local efficiency were observed in AD patients. Cortical 11 C-PBR28 uptake correlated negatively with structural integrity (standardised β = -0.375, p = 0.037) and network local efficiency (standardised β = -0.468, p < 0.001), independent of cortical thickness and Aβ deposition, while Aβ was not. Network structural integrity, small-worldness and local efficiency, and cortical thickness were positively associated with cognition. Our findings suggest cortical neuroinflammation coincide with structural and functional network disruption independent of Aβ and cortical atrophy. These findings link the brain connectivity change and pathological process in Alzheimer's disease, and suggest a pathway from neuroinflammation to systemic brain dysfunction.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Leng, F., Hinz, R., Gentleman, S., Hampshire, A., Dani, M., Brooks, D. J., et al. (2023). Neuroinflammation is independently associated with brain network dysfunction in Alzheimer's disease. Molecular psychiatry. https://doi.org/10.1038/s41380-022-01878-z
Vancouver
Leng F, Hinz R, Gentleman S, Hampshire A, Dani M, Brooks DJ, et al. Neuroinflammation is independently associated with brain network dysfunction in Alzheimer's disease. Molecular psychiatry. 2023. doi:10.1038/s41380-022-01878-z. PMID: 36474000.
BibTeX
@article{leng2023-36474000,
author = {Leng, F. and Hinz, R. and Gentleman, S. and Hampshire, A. and Dani, M. and Brooks, D. J. and Edison, P.},
title = {{Neuroinflammation is independently associated with brain network dysfunction in Alzheimer's disease}},
journal = {Molecular psychiatry},
year = {2023},
doi = {10.1038/s41380-022-01878-z},
pmid = {36474000},
url = {https://doi.org/10.1038/s41380-022-01878-z}
}
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- We hypothesised that microglial activation is independently associated with brain connectivity disruption in AD.
- Network structural integrity, small-worldness and local efficiency, and cortical thickness were positively associated with cognition.
- Our findings suggest cortical neuroinflammation coincide with structural and functional network disruption independent of Aβ and cortical atrophy.
- These findings link the brain connectivity change and pathological process in Alzheimer's disease, and suggest a pathway from neuroinflammation to systemic brain dysfunction.
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Study details
- Study designcross-sectional
- Participants42
- Evidence strengthLow
How this study scored 60/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 35 of the 58 points we could judge it on, which is 60 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 42 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36474000) |
| Free to read | 2 / 2 | Free to read |
| Points | 35 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 35 of the 58 points we could judge it on is 60 out of 100. |
| Total | 60 / 100 | — |
What each of these 20 components measures, and what this score is not →
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