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Cross-sectional and longitudinal associations of circulating bile acids and dementia: a systematic review
Zhang Y, Li J, Li J, Wang Y, Cui M, Li W, Chen X, Jiang Y.. GeroScience, 2025-07-23
Topic: Risk, prevention and care in population studies
Bile acids (BAs) may contribute to dementia by regulating neuroinflammation and influencing gut-brain axis signaling, especially in Alzheimer's disease (AD). However, their alterations in dementia development are rather complex and their impact on dementia risk remains inconclusive. To provide a comprehensive understanding of these associations, we systematically reviewed cross-sectional and longitudinal studies on circulating BAs and dementia. We conducted a systematic search of PubMed, EMBASE, and Cochrane Library from inception to August 15, 2024, for population-based observational studies investigating the changes in circulating BAs and the association between BAs and dementia risk. A total of twelve articles were eligible for inclusion, including eleven cross-sectional studies and three longitudinal studies (with two studies overlapping). Cross-sectional studies showed that, compared to cognitively normal individuals, the circulating level of primary BAs such as cholic acid (CA) is reduced, while glycochenodeoxycholic acid (GCDCA) and most secondary bile acids are increased in dementia. Longitudinal studies further support the findings and found that reduced CA, elevated GCDCA, elevated secondary BAs (glycoursodeoxycholic acid, lithocholic acid (LCA), glycolithocholic acid, and glycodeoxycholic acid (GDCA), and ratios of GDCA: CA, taurodeoxycholic acid: CA correlate with an increased risk of dementia. In addition, CA, chenodeoxycholic acid, allocholic acid, and LCA may be of significance in distinguishing AD patients from healthy people. Multiple evidence showed that reduced CA (primary BAs) level and elevated conjugated or secondary BAs levels are linked to a higher risk of dementia. Bile acids play a complex role in the pathogenesis of dementia.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zhang, Y., Li, J., Wang, Y., Cui, M., Li, W., Chen, X., et al. (2026). Cross-sectional and longitudinal associations of circulating bile acids and dementia: a systematic review. GeroScience. https://doi.org/10.1007/s11357-025-01790-8
Vancouver
Zhang Y, Li J, Wang Y, Cui M, Li W, Chen X, et al. Cross-sectional and longitudinal associations of circulating bile acids and dementia: a systematic review. GeroScience. 2026. doi:10.1007/s11357-025-01790-8. PMID: 40699484.
BibTeX
@article{zhang2026-40699484,
author = {Zhang, Y. and Li, J. and Wang, Y. and Cui, M. and Li, W. and Chen, X. and Jiang, Y.},
title = {{Cross-sectional and longitudinal associations of circulating bile acids and dementia: a systematic review}},
journal = {GeroScience},
year = {2026},
doi = {10.1007/s11357-025-01790-8},
pmid = {40699484},
url = {https://doi.org/10.1007/s11357-025-01790-8}
}
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
- Cross-sectional studies showed that, compared to cognitively normal individuals, the circulating level of primary BAs such as cholic acid (CA) is reduced, while glycochenodeoxycholic acid (GCDCA) and most secondary bile acids are increased in dementia.
- Longitudinal studies further support the findings and found that reduced CA, elevated GCDCA, elevated secondary BAs (glycoursodeoxycholic acid, lithocholic acid (LCA), glycolithocholic acid, and glycodeoxycholic acid (GDCA), and ratios of GDCA: CA, taurodeoxycholic acid: CA correlate with an increased risk of dementia.
- Multiple evidence showed that reduced CA (primary BAs) level and elevated conjugated or secondary BAs levels are linked to a higher risk of dementia.
Why it matters
Reviewing twelve population studies, the authors found that people with dementia tend to have lower levels of the primary bile acid cholic acid and higher levels of several secondary bile acids in their blood. Longitudinal studies linked this pattern to a higher risk of dementia. The authors conclude bile acids play a complex role in dementia, and these findings are associations rather than proof of cause.
Study details
- Study designcross-sectional
- Evidence strengthModerate
How this study scored 52/100
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 (GeroScience) |
| Journal's citation record | 1 / 4 | GeroScience: journal h-index 83 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A systematic review of all the studies on the question (from PubMed type “Systematic Review”) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 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 | 2 / 7 | Cited 9 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 2 / 6 | Cited 2.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Yanfeng Jiang: h-index 13 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Fudan University: institution h-index 954 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40699484) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
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