Home › Research › Mild cognitive impairment
Poor glymphatic function is associated with mild cognitive impairment and its progression to Alzheimer's disease: A DTI-ALPS study
Cuiping Bao, Hongbin Luo, Jiao Wang, Xuehuan Liu, Yiming Li, Jun Yang, Chong Chen, Rongrong Yang et al.. The Journal of Prevention of Alzheimer s Disease, 2025-04-11
Topic: Brain proteins, microglia and lab models
• Low ALPS index was significantly associated with high risk of MCI, and the risk of MCI decreased linearly with a higher ALPS index • High ALPS index was dose-dependently associated with a decreased progression from MCI to AD • High ALPS index may delay the MCI onset approximately 3.8 years among CN participants and delay MCI progression to AD by approximately 3.5 years in MCI group • Aβ in choroid plexus, tau in part of the cortex and executive function were partially mediate ALPS-AD association We aimed to explore the association between ALPS index and both risks of MCI from cognitively normal (CN) and incident AD progressed from MCI, as well as potential mediating factors. This study included 519 adults including 253 (48.75 %) CN and 266 (51.25 %) MCI participants from Alzheimer's Disease Neuroimaging Initiative. Glymphatic function (assessed by along the perivascular space [ALPS] index) was measured by diffusion tensor image at baseline. Neurobiomarkers (Aβ and tau from CSF, plasma and PET) and cognitive functions were served as mediators. Data were analyzed using Cox and Laplace regression and mediation analysis. During follow-up (median 3.6 years, interquartile range [IQR]: 2.0–4.9 years), 30 (11.86 %) participants developed MCI in the CN cohort and 73 (27.4 %) participants progressed to AD in the MCI cohort. The hazard ratios (95 % confidence intervals [CIs]) of the higher ALPS index was 0.605 (0.386–0.948) for MCI and 0.501 (0.356–0.706) for AD. In addition, participants with high ALPS index had 3.837 and 3.466 years prolonged onset of MCI and AD, separately. Aβ in choroid plexus (17.1 %), tau in cortex [Inferiortemporal (21.1 %), Middletemporal (AV1451:17.0 %, FTP:15.5 %), Superiortemporal(7.7 %), Meta_temporal (AV1451:17.5 %, FTP:16.6 %)], and executive function (14.1 %) mediated the association between ALPS and MCI-AD progression. High ALPS index decreases MCI risk and delays MCI progression to AD by approximately 3.5 years. Aβ in choroid plexus, tau in cortex, and executive function may partially mediate the MCI-AD progression in relation to ALPS index.
Key findings
- • Low ALPS index was significantly associated with high risk of MCI, and the risk of MCI decreased linearly with a higher ALPS index • High ALPS index was dose-dependently associated with a decreased progression from MCI to AD • High ALPS index may delay the MCI onset approximately 3.8 years among CN participants and delay MCI progression to AD by approximately 3.5 years in MCI group • Aβ in choroid plexus, tau in part of the cortex and executive function were partially mediate ALPS-AD association We aimed to explore the association between ALPS index and both risks of MCI from cognitively normal (CN) and incident AD progressed from MCI, as well as potential mediating factors.
Why it matters
In 519 participants, a higher ALPS index was associated with lower risk of mild cognitive impairment and slower progression to Alzheimer's disease, with estimated delays of about 3.8 and 3.5 years. This is an observational association and does not establish a treatment, cure or prevention.
Study details
- Participants519
- Evidence strengthModerate
How this study scored 53/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of Prevention of Alzheimer s Disease) |
| Journal's citation record | 0 / 4 | The Journal of Prevention of Alzheimer s Disease: journal h-index 63 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 519 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 | 3 / 7 | Cited 24 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 15.2× 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 | 2 / 4 | Cited 24 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Weili Xu: h-index 57 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Karolinska Institutet: institution h-index 1,477 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40221240) |
| Free to read | 2 / 2 | Free to read |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.tjpad.2025.100156
- PubMed: 40221240
- Original source →
- Free full text: The Journal of Prevention of Alzheimer s Disease →
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. 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
Bao, C., Luo, H., Wang, J., Liu, X., Li, Y., Yang, J., et al. (2025). Poor glymphatic function is associated with mild cognitive impairment and its progression to Alzheimer's disease: A DTI-ALPS study. The Journal of Prevention of Alzheimer s Disease. https://doi.org/10.1016/j.tjpad.2025.100156
Vancouver
Bao C, Luo H, Wang J, Liu X, Li Y, Yang J, et al. Poor glymphatic function is associated with mild cognitive impairment and its progression to Alzheimer's disease: A DTI-ALPS study. The Journal of Prevention of Alzheimer s Disease. 2025. doi:10.1016/j.tjpad.2025.100156. PMID: 40221240.
BibTeX
@article{bao2025-40221240,
author = {Bao, Cuiping and Luo, Hongbin and Wang, Jiao and Liu, Xuehuan and Li, Yiming and Yang, Jun and Chen, Chong and Yang, Rongrong and others},
title = {{Poor glymphatic function is associated with mild cognitive impairment and its progression to Alzheimer's disease: A DTI-ALPS study}},
journal = {The Journal of Prevention of Alzheimer s Disease},
year = {2025},
doi = {10.1016/j.tjpad.2025.100156},
pmid = {40221240},
url = {https://doi.org/10.1016/j.tjpad.2025.100156}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
1 study in the alzhub library lists this one in its references.