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A meta-analysis investigating the relationship between inflammation in autoimmune disease, elevated CRP, and the risk of dementia
Cooper J, Pastorello Y, Slevin M.. Frontiers in immunology, 2023-01-27
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's Disease (AD) represents the most common type of dementia and is becoming a steadily increasing challenge for health systems globally. Inflammation is developing as the main focus of research into Alzheimer's disease and has been demonstrated to be a major driver of the pathologies associated with AD. This evidence introduces an interesting research question, whether chronic inflammation due to pathologies such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) could lead to a higher risk of developing dementia. In both IBD and RA, increased levels of the inflammatory biomarker C-reactive protein (CRP) can be highlighted, the latter being directly implicated in neuroinflammation and AD. In this meta-analysis both the association between chronic inflammatory diseases and elevated levels of CRP during midlife were investigated to examine if they correlated with an augmented risk of dementia. Moreover, the association between increased CRP and modifications in the permeability of the Blood Brain Barrier (BBB) in the presence of CRP is explored. The results displayed that the odds ratio for IBD and dementia was 1.91 [1.15-3.15], for RA it was 1.90 [1.09-3.32] following sensitivity analysis and for CRP it was 1.62 [1.22-2.15]. These results demonstrate a higher risk of dementia in patients presenting chronic inflammation and that exists an independent association with high CRP in midlife. This paper builds on published research that suggest a critical role for CRP both in stroke and AD and provides an analysis on currently published research on multiple diseases (IBD and RA) in which CRP is raised as well as chronically elevated. CRP and the associated risk of dementia and further research indicated that the monomeric form of CRP can infiltrate the BBB/be released from damaged micro-vessels to access the brain. This meta-analysis provides first-time evidence that chronic elevation of CRP in autoimmune diseases is directly associated with an increased risk of later development of Alzheimer's disease. Therefore, greater priority should be provided to the effective control of inflammation in patients with chronic inflammatory or autoimmune conditions and further long-term assessment of circulating CRP might inform of an individual's relative risk of developing dementia.
Key findings
- Inflammation is developing as the main focus of research into Alzheimer's disease and has been demonstrated to be a major driver of the pathologies associated with AD.
- This evidence introduces an interesting research question, whether chronic inflammation due to pathologies such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) could lead to a higher risk of developing dementia.
- The results displayed that the odds ratio for IBD and dementia was 1.91 [1.15-3.15], for RA it was 1.90 [1.09-3.32] following sensitivity analysis and for CRP it was 1.62 [1.22-2.15].
- These results demonstrate a higher risk of dementia in patients presenting chronic inflammation and that exists an independent association with high CRP in midlife.
- CRP and the associated risk of dementia and further research indicated that the monomeric form of CRP can infiltrate the BBB/be released from damaged micro-vessels to access the brain.
Why it matters
This meta-analysis found that inflammatory bowel disease (odds ratio 1.91) and rheumatoid arthritis (1.90) were linked to a higher risk of dementia, as was high C-reactive protein (CRP), an inflammation marker, in midlife (1.62). The authors say people with chronic inflammation showed a higher dementia risk and that better control of inflammation in people with chronic inflammatory or autoimmune conditions should be a priority. Tracking CRP over time might help estimate a person's risk.
Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 63/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in immunology) |
| Journal's citation record | 3 / 4 | Frontiers in Immunology: journal h-index 352 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 4 / 7 | Cited 75 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.0 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 3 / 6 | Cited 4.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 3 / 4 | Cited 68 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author MARK A. SLEVIN: h-index 51 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Manchester Metropolitan University: institution h-index 356 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36776896) |
| Free to read | 2 / 2 | Free to read |
| Total | 63 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fimmu.2023.1087571
- PubMed: 36776896
- Original source →
- Free full text: Frontiers in Immunology →
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. Check the citation against the original before you use it.
APA 7th
Cooper, J., Pastorello, Y., & Slevin, M. (2023). A meta-analysis investigating the relationship between inflammation in autoimmune disease, elevated CRP, and the risk of dementia. Frontiers in immunology. https://doi.org/10.3389/fimmu.2023.1087571
Vancouver
Cooper J, Pastorello Y, Slevin M. A meta-analysis investigating the relationship between inflammation in autoimmune disease, elevated CRP, and the risk of dementia. Frontiers in immunology. 2023. doi:10.3389/fimmu.2023.1087571. PMID: 36776896.
BibTeX
@article{cooper2023-36776896,
author = {Cooper, J. and Pastorello, Y. and Slevin, M.},
title = {{A meta-analysis investigating the relationship between inflammation in autoimmune disease, elevated CRP, and the risk of dementia}},
journal = {Frontiers in immunology},
year = {2023},
doi = {10.3389/fimmu.2023.1087571},
pmid = {36776896},
url = {https://doi.org/10.3389/fimmu.2023.1087571}
}
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