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Inflammatory markers in type 2 diabetes with vs. without cognitive impairment; a systematic review and meta-analysis
Anita NZ, Zebarth J, Chan B, Wu CY, Syed T, Shahrul D, Nguyen MM, Pakosh M et al.. Brain, behavior, and immunity, 2021-11-20
Topic: Risk, prevention and care in population studies
People with type 2 diabetes mellitus (T2DM) are at increased risk of mild cognitive impairment and dementia. Systemic inflammation has been proposed as a common risk factor. This study aimed to summarize the clinical data pertaining to peripheral blood inflammatory markers. We identified original peer-reviewed articles reporting blood inflammatory marker concentrations in groups of people with a T2DM diagnosis who have cognitive impairment (CI; including mild cognitive impairment, Alzheimer's disease, vascular cognitive impairment) vs. normal cognition (NC). Between-group standardized mean differences (SMD) were summarized in random effects meta-analyses. From 2108 records, data were combined quantitatively from 40 studies. Concentrations of interleukin-6 (IL-6; N CI /N NC = 934/3154, SMD 0.74 95% confidence interval [0.07, 1.42], Z 5 = 2.15, p = 0.03; I 2 = 98.08%), C-reactive protein (CRP; N CI /N NC = 1610/4363, SMD 0.80 [0.50, 1.11], Z 14 = 5.25, p 2 = 94.59%), soluble vascular cell adhesion molecule-1 (sVCAM-1; N CI /N NC = 104/1063, SMD 1.64 95% confidence interval [0.21, 3.07], Z 2 = 2.25, p = 0.02; I 2 = 95.19%), and advanced glycation end products (AGEs; N CI /N NC = 227/317, SMD 0.84 95% confidence interval [0.41, 1.27], Z 2 = 3.82, p 2 = 81.07%) were higher among CI groups compared to NC. Brain derived neurotropic factor (BDNF) concentrations were significantly lower in CI compared to NC (N CI /N NC = 848/2063, SMD -0.67 95% confidence interval [-0.99, -0.35], Z 3 = -4.09, p 2 = 89.20%). Cognitive impairment among people with T2DM was associated with systemic inflammation and lower BDNF concentrations. These inflammatory characteristics support an increased inflammatory-vascular interaction associated with cognitive impairment in T2DM. PROSPERO (CRD42020188625).
Key findings
- People with type 2 diabetes mellitus (T2DM) are at increased risk of mild cognitive impairment and dementia.
- Concentrations of interleukin-6 (IL-6; N CI /N NC = 934/3154, SMD 0.74 95% confidence interval [0.07, 1.42], Z 5 = 2.15, p = 0.03; I 2 = 98.08%), C-reactive protein (CRP; N CI /N NC = 1610/4363, SMD 0.80 [0.50, 1.11], Z 14 = 5.25, p < 0.01; I 2 = 94.59%), soluble vascular cell adhesion molecule-1 (sVCAM-1; N CI /N NC = 104/1063, SMD 1.64 95% confidence interval [0.21, 3.07], Z 2 = 2.25, p = 0.02; I 2 = 95.19%), and advanced glycation end products (AGEs; N CI /N NC = 227/317, SMD 0.84 95% confidence interval [0.41, 1.27], Z 2 = 3.82, p < 0.01; I 2 = 81.07%) were higher among CI groups compared to NC.
- Brain derived neurotropic factor (BDNF) concentrations were significantly lower in CI compared to NC (N CI /N NC = 848/2063, SMD -0.67 95% confidence interval [-0.99, -0.35], Z 3 = -4.09, p 2 = 89.20%).
- Cognitive impairment among people with T2DM was associated with systemic inflammation and lower BDNF concentrations.
- These inflammatory characteristics support an increased inflammatory-vascular interaction associated with cognitive impairment in T2DM.
Why it matters
Combining data from 40 studies, this meta-analysis found that people with type 2 diabetes who had cognitive impairment had higher blood levels of inflammatory markers such as IL-6, C-reactive protein, sVCAM-1 and advanced glycation end products than those with normal cognition. Levels of BDNF, a protein that supports nerve cells, were lower. These associations support the idea that inflammation and blood-vessel problems are linked to cognitive impairment in diabetes, though they do not prove cause.
Study details
- Study designmeta-analysis
- Effect size98.08%; 94.59%; 95.19%
- Evidence strengthHigh
How this study scored 61/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for sample size and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Brain, behavior, and immunity) |
| Journal's citation record | 2 / 4 | Brain Behavior and Immunity: journal h-index 249 (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 | 2022 — 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 68 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.3 citations a year over 6 year(s) since 2022 |
| 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 | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 43 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Walter Swardfager: h-index 47 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Toronto: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34808290) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 61 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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
Anita, N. Z., Zebarth, J., Chan, B., Wu, C. Y., Syed, T., Shahrul, D., et al. (2022). Inflammatory markers in type 2 diabetes with vs. without cognitive impairment; a systematic review and meta-analysis. Brain, behavior, and immunity. https://doi.org/10.1016/j.bbi.2021.11.005
Vancouver
Anita NZ, Zebarth J, Chan B, Wu CY, Syed T, Shahrul D, et al. Inflammatory markers in type 2 diabetes with vs. without cognitive impairment; a systematic review and meta-analysis. Brain, behavior, and immunity. 2022. doi:10.1016/j.bbi.2021.11.005. PMID: 34808290.
BibTeX
@article{anita2022-34808290,
author = {Anita, N. Z. and Zebarth, J. and Chan, B. and Wu, C. Y. and Syed, T. and Shahrul, D. and Nguyen, M. M. and Pakosh, M. and others},
title = {{Inflammatory markers in type 2 diabetes with vs. without cognitive impairment; a systematic review and meta-analysis}},
journal = {Brain, behavior, and immunity},
year = {2022},
doi = {10.1016/j.bbi.2021.11.005},
pmid = {34808290},
url = {https://doi.org/10.1016/j.bbi.2021.11.005}
}
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