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Association between lipocalin-2 and mild cognitive impairment or dementia: A systematic review and meta-analysis of population-based evidence
Li X, Wang X, Guo L, Wu K, Wang L, Rao L, Liu X, Kang C et al.. Ageing research reviews, 2023-06-15
Topic: Risk, prevention and care in population studies
Background The associations between lipocalin-2 (LCN2) with mild cognitive impairment (MCI) and dementia have gained growing interest. However, population-based studies have yielded inconsistent findings. Therefore, we conducted this essential systematic review and meta-analysis to analyze and summarize the existing population-based evidence. Methods PubMed, EMBASE, and Web of Science were systematically searched until Mar 18, 2022. Meta-analysis was performed to generate the standard mean difference (SMD) of peripheral blood and cerebrospinal fluid (CSF) LCN2. A qualitative review was performed to summarize the evidence from postmortem brain tissue studies. Results In peripheral blood, the overall pooled results showed no significant difference in LCN2 across Alzheimer's disease (AD), MCI and control groups. Further subgroup analysis revealed higher serum LCN2 levels in AD compared to controls (SMD =1.28 [0.44;2.13], p = 0.003), while the difference remained insignificant in plasma (SMD =0.04 [-0.82;0.90], p = 0.931). Besides, peripheral blood LCN2 were higher in AD when age difference between AD and controls ≥ 4 years (SMD =1.21 [0.37;2.06], p = 0.005). In CSF, no differences were found in LCN2 across groups of AD, MCI and controls. However, CSF LCN2 was higher in vascular dementia (VaD) compared to controls (SMD =1.02 [0.17;1.87], p = 0.018), as well as compared to AD (SMD =1.19 [0.58;1.80], p Conclusion The difference in peripheral blood LCN2 between AD and controls may be affected by the type of biofluid and age. No differences were found in CSF LCN2 across AD, MCI and controls groups. In contrast, CSF LCN2 was elevated in VaD patients. Moreover, LCN2 was increased in AD-related brain areas and cells in AD, while in infarcts-related brain areas and cells in MD.
Key findings
- Results In peripheral blood, the overall pooled results showed no significant difference in LCN2 across Alzheimer's disease (AD), MCI and control groups.
- Further subgroup analysis revealed higher serum LCN2 levels in AD compared to controls (SMD =1.28 [0.44;2.13], p = 0.003), while the difference remained insignificant in plasma (SMD =0.04 [-0.82;0.90], p = 0.931).
- However, CSF LCN2 was higher in vascular dementia (VaD) compared to controls (SMD =1.02 [0.17;1.87], p = 0.018), as well as compared to AD (SMD =1.19 [0.58;1.80], p Conclusion The difference in peripheral blood LCN2 between AD and controls may be affected by the type of biofluid and age.
Why it matters
Pooling population studies, this meta-analysis found no overall difference in blood levels of lipocalin-2 (LCN2), an inflammation-related protein, between people with Alzheimer's, mild cognitive impairment and controls, though serum levels were higher in Alzheimer's. In spinal fluid there was no difference for Alzheimer's or MCI, but levels were raised in vascular dementia. The authors conclude that blood differences between Alzheimer's and controls may depend on the type of sample and on age.
Study details
- Study designsystematic review
- Evidence strengthHigh
How this study scored 54/100
Published in a peer-reviewed journal, and it is a systematic review of all the studies on the question. 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 (Ageing research reviews) |
| Journal's citation record | 2 / 4 | Ageing Research Reviews: journal h-index 225 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A systematic review of all the studies on the question |
| 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 | 3 / 7 | Cited 21 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.2 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 2 / 6 | Cited 1.3× 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 | 2 / 4 | Cited 21 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Ciyong Lu: h-index 45 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Sun Yat-sen University: institution h-index 851 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37330019) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 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
Li, X., Wang, X., Guo, L., Wu, K., Wang, L., Rao, L., et al. (2023). Association between lipocalin-2 and mild cognitive impairment or dementia: A systematic review and meta-analysis of population-based evidence. Ageing research reviews. https://doi.org/10.1016/j.arr.2023.101984
Vancouver
Li X, Wang X, Guo L, Wu K, Wang L, Rao L, et al. Association between lipocalin-2 and mild cognitive impairment or dementia: A systematic review and meta-analysis of population-based evidence. Ageing research reviews. 2023. doi:10.1016/j.arr.2023.101984. PMID: 37330019.
BibTeX
@article{li2023-37330019,
author = {Li, X. and Wang, X. and Guo, L. and Wu, K. and Wang, L. and Rao, L. and Liu, X. and Kang, C. and others},
title = {{Association between lipocalin-2 and mild cognitive impairment or dementia: A systematic review and meta-analysis of population-based evidence}},
journal = {Ageing research reviews},
year = {2023},
doi = {10.1016/j.arr.2023.101984},
pmid = {37330019},
url = {https://doi.org/10.1016/j.arr.2023.101984}
}
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