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Glymphatic system dysfunction as a predictor of cognitive decline and incident dementia
Chengqian Li, W. Li, Zi-Yue Liu, Fei-Fei Zhai, Fei Han, Mingli Li, Lixin Zhou, Jun Ni et al.. Journal of Alzheimer s Disease, 2026-01-21
Topic: Risk, prevention and care in population studies
Background Cognitive decline and incident dementia in ageing populations have been linked to brain parenchymal injury and the ALPS index (ALPS-I). Objective This investigation aimed to elucidate whether the baseline ALPS-I could predict incident dementia and cognitive decline in this population. Methods In total, 973 dementia-free participants from the Shunyi Study (mean age, 57 years; 37% male) received MRI between 2013 and 2016 to quantify the ALPS-I. The longitudinal relationships between the ALPS-I and cognitive deterioration in various cognitive areas were evaluated via linear mixed models. Cox proportional hazard models were utilized to explore the link between the index and incident dementia. Mediation assessments were carried out to identify the potential mediating effects of brain parenchymal injury on the link between the ALPS-I and cognition. Results The baseline ALPS-I predicted longitudinal changes in global cognition (Montreal Cognitive Assessment), language (verbal fluency test), visuospatial perception (block design subtest of Wechsler intelligence scale), and executive function (Trail Making Test). A lower score was markedly associated with a higher incident dementia risk. Mediation analysis revealed that fractional anisotropy mediated the associations between the ALPS-I and executive function (mediation effect: 21.9%) and visuospatial perception (mediation effect: 68.8%). The white matter hyperintensity fraction was found to mediate the link between the ALPS-I and global cognition (mediation effect: 55.0%). Conclusions This longitudinal evidence supports a link between the ALPS-I and cognitive degeneration. Furthermore, the link is mediated by subcortical parenchymal injury.
Key findings
- Results The baseline ALPS-I predicted longitudinal changes in global cognition (Montreal Cognitive Assessment), language (verbal fluency test), visuospatial perception (block design subtest of Wechsler intelligence scale), and executive function (Trail Making Test).
- A lower score was markedly associated with a higher incident dementia risk.
- Mediation analysis revealed that fractional anisotropy mediated the associations between the ALPS-I and executive function (mediation effect: 21.9%) and visuospatial perception (mediation effect: 68.8%).
Why it matters
In 973 dementia-free participants, a lower baseline ALPS index (a marker of glymphatic function) predicted later cognitive decline and higher incident dementia risk. This suggests the ALPS index could help identify people at risk, but the study does not show that targeting it prevents dementia.
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Study details
- Study designlongitudinal study
- Effect size21.9%; 68.8%; 55.0%
- Evidence strengthModerate
How this study scored 48/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer s Disease) |
| Journal's citation record | 2 / 4 | Journal of Alzheimer s Disease: journal h-index 218 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| 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 | 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 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 9.5× 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 | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Yi‐Cheng Zhu: h-index 46 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Chinese Academy of Medical Sciences & Peking Union Medical College: institution h-index 950 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41562366) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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, C., Li, W., Liu, Z.-Y., Zhai, F.-F., Han, F., Li, M., et al. (2026). Glymphatic system dysfunction as a predictor of cognitive decline and incident dementia. Journal of Alzheimer s Disease. https://doi.org/10.1177/13872877251411493
Vancouver
Li C, Li W, Liu Z.-Y, Zhai F.-F, Han F, Li M, et al. Glymphatic system dysfunction as a predictor of cognitive decline and incident dementia. Journal of Alzheimer s Disease. 2026. doi:10.1177/13872877251411493. PMID: 41562366.
BibTeX
@article{li2026-41562366,
author = {Li, Chengqian and Li, W. and Liu, Zi-Yue and Zhai, Fei-Fei and Han, Fei and Li, Mingli and Zhou, Lixin and Ni, Jun and others},
title = {{Glymphatic system dysfunction as a predictor of cognitive decline and incident dementia}},
journal = {Journal of Alzheimer s Disease},
year = {2026},
doi = {10.1177/13872877251411493},
pmid = {41562366},
url = {https://doi.org/10.1177/13872877251411493}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.