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Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease
Hsu JL, Wei YC, Toh CH, Hsiao IT, Lin KJ, Yen TC, Liao MF, Ro LS.. Annals of neurology, 2022-10-26
Topic: Amyloid, tau and blood-test diagnosis
Objective The glymphatic system cleans amyloid and tau proteins from the brain in animal studies of Alzheimer disease (AD). However, there is no direct evidence showing this in humans. Methods Participants (n = 50, 62.6 ± 5.4 years old, 36 women) with AD and normal controls underwent amyloid positron emission tomography (PET), tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation. Whole-brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS). Results ALPS-indexes showed negative correlations with deposition of amyloid and tau on PET images and positive correlations with cognitive scores even after adjusting for age, sex, years of education, and APOE4 genotype covariates in multiple AD-related brain regions (all p Interpretation Glymphatic system activity may act as a significant mediator in AD-related cognitive dysfunction even after adjusting for multiple covariates and gray matter volumes. ALPS-index may provide useful disease progression or treatment biomarkers for patients with AD as an indicator of modulation of glymphatic activity. ANN NEUROL 2023;93:164-174.
Key findings
- Results ALPS-indexes showed negative correlations with deposition of amyloid and tau on PET images and positive correlations with cognitive scores even after adjusting for age, sex, years of education, and APOE4 genotype covariates in multiple AD-related brain regions (all p < 0.05).
Why it matters
In 50 participants, a measure of glymphatic system activity correlated negatively with amyloid and tau deposition on PET and positively with cognitive scores. The authors note this is an association and suggest the measure could serve as a progression or treatment biomarker, but the study does not show that altering glymphatic activity treats or prevents Alzheimer's.
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Study details
- Participants50
- Evidence strengthLow
How this study scored 58/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (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 | 1 / 5 | Rated “low” 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 | 1 / 4 | 50 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 | 5 / 7 | Cited 262 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 52.4 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 4 / 6 | Cited 18.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 4 / 4 | Cited 229 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Long‐Sun Ro: h-index 31 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | National Yang Ming Chiao Tung University: institution h-index 451 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36214568) |
| Free to read | 2 / 2 | Free to read |
| Total | 58 / 100 | — |
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Read the original
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 names 8 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.
APA 7th
Hsu, J. L., Wei, Y. C., Toh, C. H., Hsiao, I. T., Lin, K. J., Yen, T. C., et al. (2023). Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease. Annals of neurology. https://doi.org/10.1002/ana.26516
Vancouver
Hsu JL, Wei YC, Toh CH, Hsiao IT, Lin KJ, Yen TC, et al. Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease. Annals of neurology. 2023. doi:10.1002/ana.26516. PMID: 36214568.
BibTeX
@article{hsu2023-36214568,
author = {Hsu, J. L. and Wei, Y. C. and Toh, C. H. and Hsiao, I. T. and Lin, K. J. and Yen, T. C. and Liao, M. F. and Ro, L. S.},
title = {{Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease}},
journal = {Annals of neurology},
year = {2023},
doi = {10.1002/ana.26516},
pmid = {36214568},
url = {https://doi.org/10.1002/ana.26516}
}
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