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Impaired Glymphatic Clearance, Measured Using Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS), is Linked to Poor Cognitive Outcomes in Parkinson's Disease
Zarkali A, Thomas G, Paterson R, Hannaway N, Dobreva I, Heslegrave AJ, Veleva E, Zetterberg H et al.. Movement disorders : official journal of the Movement Disorder Society, 2025-08-07
Topic: Brain proteins, microglia and lab models
Background Impaired glymphatic clearance may contribute to pathological accumulations in Parkinson's (PD), but how it interacts with other processes causing dementia remains unclear. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) has been proposed as an indirect proxy for glymphatic clearance. Objectives To clarify DTI-ALPS' relationship with cognition in PD, and its relationship with established imaging markers. Methods We assessed DTI-ALPS in 98 PD patients (31 PD poor outcomes: dementia, mild cognitive impairment, frailty, or death within a 3-year follow-up; 67 PD good outcomes) and 28 controls. We assessed DTI-ALPS' relationship to cognition, white matter (fiber cross-section), cortical thickness, iron accumulation (quantitative susceptibility mapping [QSM]), and plasma markers [phosphorylated tau-181 (p-tau181 and neurofilament light (NfL)] cross-sectionally and longitudinally). Results DTI-ALPS was lower in PD-poor outcomes compared with PD good outcomes and controls (P = 0.005) with further longitudinal reductions only in PD poor outcomes (group × time interaction: β = -0.013, P = 0.021). Lower DTI-ALPS was associated with lower fiber cross-section in PD, at baseline and longitudinally but with different spatial distribution from white matter changes relating to PD cognition. There was no correlation between baseline DTI-ALPS and plasma p-tau181 (P = 0.642), NFL (P = 0.448), or baseline cortical thickness. Lower DTI-ALPS was associated with accelerated cortical thinning within left precentral gyrus and changes in brain iron distribution. Conclusions PD patients who develop poor outcomes show lower DTI-ALPS, potentially reflecting impaired glymphatic clearance. DTI-ALPS correlated with white matter integrity and brain iron accumulation. However, both showed different spatial distribution than that seen in PD dementia, suggesting DTI-ALPS captures a distinct contribution to cognitive decline. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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APA 7th
Zarkali, A., Thomas, G., Paterson, R., Hannaway, N., Dobreva, I., Heslegrave, A. J., et al. (2025). Impaired Glymphatic Clearance, Measured Using Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS), is Linked to Poor Cognitive Outcomes in Parkinson's Disease. Movement disorders : official journal of the Movement Disorder Society. https://doi.org/10.1002/mds.30325
Vancouver
Zarkali A, Thomas G, Paterson R, Hannaway N, Dobreva I, Heslegrave AJ, et al. Impaired Glymphatic Clearance, Measured Using Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS), is Linked to Poor Cognitive Outcomes in Parkinson's Disease. Movement disorders : official journal of the Movement Disorder Society. 2025. doi:10.1002/mds.30325. PMID: 40776573.
BibTeX
@article{zarkali2025-40776573,
author = {Zarkali, A. and Thomas, G. and Paterson, R. and Hannaway, N. and Dobreva, I. and Heslegrave, A. J. and Veleva, E. and Zetterberg, H. and others},
title = {{Impaired Glymphatic Clearance, Measured Using Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS), is Linked to Poor Cognitive Outcomes in Parkinson's Disease}},
journal = {Movement disorders : official journal of the Movement Disorder Society},
year = {2025},
doi = {10.1002/mds.30325},
pmid = {40776573},
url = {https://doi.org/10.1002/mds.30325}
}
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Key findings
- Results DTI-ALPS was lower in PD-poor outcomes compared with PD good outcomes and controls (P = 0.005) with further longitudinal reductions only in PD poor outcomes (group × time interaction: β = -0.013, P = 0.021).
- Lower DTI-ALPS was associated with lower fiber cross-section in PD, at baseline and longitudinally but with different spatial distribution from white matter changes relating to PD cognition.
- Lower DTI-ALPS was associated with accelerated cortical thinning within left precentral gyrus and changes in brain iron distribution.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 60/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 35 of the 58 points we could judge it on, which is 60 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Movement disorders : official journal of the Movement Disorder Society) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 4 / 5 | 2025 — within 3 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 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40776573) |
| Free to read | 2 / 2 | Free to read |
| Points | 35 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 35 of the 58 points we could judge it on is 60 out of 100. |
| Total | 60 / 100 | — |
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