Home › Research › Biomarkers
Associations of Microbleeds and Their Topography With Imaging and CSF Biomarkers of Alzheimer Pathology in Individuals With Down Syndrome
Zsadanyi SE, Morcillo-Nieto AO, Aranha MR, Aragón I, Arriola-Infante JE, Vaqué-Alcázar L, Montal V, Pegueroles J et al.. Neurology, 2024-07-29
Topic: Brain proteins, microglia and lab models
Background and objectives Cerebral hemorrhages are an exclusion criterion and potential adverse effect of antiamyloid agents. It is, therefore, critical to characterize the natural history of cerebral microbleeds in populations genetically predisposed to Alzheimer disease (AD), such as Down syndrome (DS). We aimed to assess microbleed emergence in adults with DS across the AD spectrum, defining their topography and associations with clinical variables, cognitive outcomes, and fluid and neuroimaging biomarkers. Methods This cross-sectional study included participants aged 18 years or older from the Down-Alzheimer Barcelona Neuroimaging Initiative and Sant Pau Initiative on Neurodegeneration with T1-weighted and susceptibility-weighted images. Participants underwent comprehensive assessments, including apolipoprotein E ( APOE ) genotyping; fluid and plasma determinations of beta-amyloid, tau, and neurofilament light; cognitive outcomes (Cambridge Cognitive Examination and modified Cued Recall Test); and vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia). We manually segmented microbleeds and characterized their topography. Associations between microbleed severity and AD biomarkers were explored using between-group comparisons (none vs 1 vs 2+) and multivariate linear models. Results We included 276 individuals with DS and 158 healthy euploid controls (mean age = 47.8 years, 50.92% female). Individuals with DS were more likely to have microbleeds than controls (20% vs 8.9%, p 60 years) and AD clinical stage (12.42% asymptomatic, 27.9% prodromal, 35.09% dementia) were more common in APOE ε4 carriers (26% vs 18.3% noncarriers, p = 0.008), but not associated with vascular risk factors ( p > 0.05). Microbleeds were predominantly posterior (cerebellum 33.66%; occipital 14.85%; temporal 21.29%) in participants with DS. Associations with microbleed severity were found for neuroimaging and fluid AD biomarkers, but only hippocampal volumes (standardized β = -0.18 [-0.31, -0.06], p p Discussion In participants with DS, microbleeds present with a posterior, lobar predominance, are associated with disease severity, but do not affect cognitive performance. These results suggest an interplay between AD pathology and vascular lesions, implicating microbleeds as a risk factor limiting the use of antiamyloid agents in this population.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zsadanyi, S. E., Morcillo-Nieto, A. O., Aranha, M. R., Aragón, I., Arriola-Infante, J. E., Vaqué-Alcázar, L., et al. (2024). Associations of Microbleeds and Their Topography With Imaging and CSF Biomarkers of Alzheimer Pathology in Individuals With Down Syndrome. Neurology. https://doi.org/10.1212/wnl.0000000000209676
Vancouver
Zsadanyi SE, Morcillo-Nieto AO, Aranha MR, Aragón I, Arriola-Infante JE, Vaqué-Alcázar L, et al. Associations of Microbleeds and Their Topography With Imaging and CSF Biomarkers of Alzheimer Pathology in Individuals With Down Syndrome. Neurology. 2024. doi:10.1212/wnl.0000000000209676. PMID: 39074338.
BibTeX
@article{zsadanyi2024-39074338,
author = {Zsadanyi, S. E. and Morcillo-Nieto, A. O. and Aranha, M. R. and Aragón, I. and Arriola-Infante, J. E. and Vaqué-Alcázar, L. and Montal, V. and Pegueroles, J. and others},
title = {{Associations of Microbleeds and Their Topography With Imaging and CSF Biomarkers of Alzheimer Pathology in Individuals With Down Syndrome}},
journal = {Neurology},
year = {2024},
doi = {10.1212/wnl.0000000000209676},
pmid = {39074338},
url = {https://doi.org/10.1212/wnl.0000000000209676}
}
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.
Key findings
- Results We included 276 individuals with DS and 158 healthy euploid controls (mean age = 47.8 years, 50.92% female).
- Individuals with DS were more likely to have microbleeds than controls (20% vs 8.9%, p < 0.001), with more severe presentation (12% with 2+ vs 1.9%).
- Associations with microbleed severity were found for neuroimaging and fluid AD biomarkers, but only hippocampal volumes (standardized β = -0.18 [-0.31, -0.06], p < 0.005) and CSF p-tau-181 concentrations (β = 0.26 [0.12, 0.41], p < 0.005) survived regression controlling for age and disease stage, respectively.
- These results suggest an interplay between AD pathology and vascular lesions, implicating microbleeds as a risk factor limiting the use of antiamyloid agents in this population.
Why it matters
In this cross-sectional study, adults with Down syndrome were more likely to have cerebral microbleeds than controls, and microbleed severity was associated with imaging and fluid Alzheimer disease biomarkers. The authors note that cerebral hemorrhages are an exclusion criterion and potential adverse effect of antiamyloid agents, so characterizing microbleeds matters for that context.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designcross-sectional
- Participants276
- Effect size50.92%; 8.9%; 12.42%
- Evidence strengthLow
How this study scored 55/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 276 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 14 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.5 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 3 / 6 | Cited 3.8× 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 | 1 / 4 | Cited 14 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Alexandre Bejanin: h-index 36 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Universitat Autònoma de Barcelona: institution h-index 782 (OpenAlex) |
| Multicenter collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39074338) |
| Free to read | 2 / 2 | Free to read |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Related
Studies in the library that share something with this one. The line above each title says what.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 13.
Later studies that cite this one
1 study in the alzhub library lists this one in its references.
Related studies in Biomarkers from nearby years
Also tagged “down”
527 studies in the library carry the topic tag “down”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 527 tagged studies.