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Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer’s disease copathologies
Elijah E Mak, Robert I. Reid, Scott A. Przybelski, Angela J. Fought, Timothy G. Lesnick, Christopher G. Schwarz, Matthew L. Senjem, Sheelakumari Raghavan et al.. npj Parkinson s Disease, 2025-05-12
Topic: Amyloid, tau and blood-test diagnosis
Dementia with Lewy bodies (DLB) frequently coexists with Alzheimer's disease pathology, yet the pattern of cortical microstructural injury and its relationship with amyloid, tau, and cerebrovascular pathologies remains unclear. We applied neurite orientation dispersion and density imaging (NODDI) to assess cortical microstructural integrity in 57 individuals within the DLB spectrum and 57 age- and sex-matched cognitively unimpaired controls by quantifying mean diffusivity (MD), tissue-weighted neurite density index (tNDI), orientation dispersion index (ODI), and free water fraction (FWF). Amyloid and tau levels were measured using PiB and Flortaucipir PET imaging. Compared to controls, DLB exhibited increased MD and FWF, reduced tNDI across multiple regions, and focal ODI reductions in the occipital cortex. Structural equation modeling revealed that APOE genotype influenced amyloid levels, which elevated tau, leading to microstructural injury. These findings highlight the role of AD pathology in DLB neurodegeneration, advocating for multi-target therapeutic approaches addressing both AD and DLB-specific pathologies.
Key findings
- Compared to controls, DLB exhibited increased MD and FWF, reduced tNDI across multiple regions, and focal ODI reductions in the occipital cortex.
- Structural equation modeling revealed that APOE genotype influenced amyloid levels, which elevated tau, leading to microstructural injury.
- These findings highlight the role of AD pathology in DLB neurodegeneration, advocating for multi-target therapeutic approaches addressing both AD and DLB-specific pathologies.
Why it matters
In people with dementia with Lewy bodies, brain imaging showed signs of cortical microstructural injury, and modeling suggested APOE genotype influenced amyloid levels, which raised tau, leading to this injury. The authors advocate for multi-target therapeutic approaches addressing both Alzheimer's and Lewy body pathologies, but this study itself did not test a treatment.
Study details
- Participants57
- Evidence strengthLow
How this study scored 48/100
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 (npj Parkinson s Disease) |
| Journal's citation record | 1 / 4 | Npj Parkinson s Disease: journal h-index 87 (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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 57 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 | 2 / 7 | Cited 10 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 6.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 1 / 4 | Cited 10 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Kejal Kantarci: h-index 103 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40355490) |
| Free to read | 2 / 2 | Free to read |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41531-025-00944-x
- PubMed: 40355490
- Original source →
- Free full text: npj Parkinson 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
Mak, E. E., Reid, R. I., Przybelski, S. A., Fought, A. J., Lesnick, T. G., Schwarz, C. G., et al. (2025). Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer’s disease copathologies. npj Parkinson s Disease. https://doi.org/10.1038/s41531-025-00944-x
Vancouver
Mak EE, Reid RI, Przybelski SA, Fought AJ, Lesnick TG, Schwarz CG, et al. Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer’s disease copathologies. npj Parkinson s Disease. 2025. doi:10.1038/s41531-025-00944-x. PMID: 40355490.
BibTeX
@article{mak2025-40355490,
author = {Mak, Elijah E and Reid, Robert I. and Przybelski, Scott A. and Fought, Angela J. and Lesnick, Timothy G. and Schwarz, Christopher G. and Senjem, Matthew L. and Raghavan, Sheelakumari and others},
title = {{Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer’s disease copathologies}},
journal = {npj Parkinson s Disease},
year = {2025},
doi = {10.1038/s41531-025-00944-x},
pmid = {40355490},
url = {https://doi.org/10.1038/s41531-025-00944-x}
}
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