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Assessing amyloid PET positivity and cognitive function in Down syndrome to guide clinical trials targeting amyloid
Krasny S, Yan C, Hartley SL, Handen BL, Wisch JK, Boehrwinkle AH, Ances BM, Rafii MS et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024-06-28
Topic: Brain proteins, microglia and lab models
Introduction Trisomy 21, or Down syndrome (DS), predisposes individuals to early-onset Alzheimer's disease (AD). While monoclonal antibodies (mAbs) targeting amyloid are approved for older AD patients, their efficacy in DS remains unexplored. This study examines amyloid positron emission tomography (PET) positivity (A+), memory function, and clinical status across ages in DS to guide mAb trial designs. Methods Cross-sectional data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) was analyzed. PET amyloid beta in Centiloids classified amyloid status using various cutoffs. Episodic memory was assessed using the modified Cued Recall Test, and clinical status was determined through consensus processes. Results Four hundred nine DS adults (mean age = 44.83 years) were evaluated. A+ rates increased with age, with mean amyloid load rising significantly. Memory decline and cognitive impairment are also correlated with age. Discussion These findings emphasize the necessity of tailoring mAb trials for DS, considering age-related AD characteristics. Highlights There is rapid increase in prevalence of amyloid beta (Aβ) positron emission tomography (PET) positivity in Down syndrome (DS) after the age of 40 years. Aβ PET positivity thresholds have significant impact on prevalence rates in DS. There is a significant lag between Aβ PET positivity and clinical symptom onset in DS.
Key findings
- Results Four hundred nine DS adults (mean age = 44.83 years) were evaluated.
- A+ rates increased with age, with mean amyloid load rising significantly.
- Discussion These findings emphasize the necessity of tailoring mAb trials for DS, considering age-related AD characteristics.
- Aβ PET positivity thresholds have significant impact on prevalence rates in DS.
- There is a significant lag between Aβ PET positivity and clinical symptom onset in DS.
Why it matters
Among 409 adults with Down syndrome, amyloid PET positivity increased with age, and there was a significant lag between amyloid positivity and clinical symptom onset. This cross-sectional study is intended to guide monoclonal antibody trial designs and does not itself test any treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Study designcross-sectional
- Evidence strengthLow
How this study scored 52/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 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 | 3 / 7 | Cited 17 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.2 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 3 / 6 | Cited 4.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 17 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Michael S. Rafii: h-index 50 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38940611) |
| Free to read | 2 / 2 | Free to read |
| Total | 52 / 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'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
Krasny, S., Yan, C., Hartley, S. L., Handen, B. L., Wisch, J. K., Boehrwinkle, A. H., et al. (2024). Assessing amyloid PET positivity and cognitive function in Down syndrome to guide clinical trials targeting amyloid. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.14068
Vancouver
Krasny S, Yan C, Hartley SL, Handen BL, Wisch JK, Boehrwinkle AH, et al. Assessing amyloid PET positivity and cognitive function in Down syndrome to guide clinical trials targeting amyloid. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. doi:10.1002/alz.14068. PMID: 38940611.
BibTeX
@article{krasny2024-38940611,
author = {Krasny, S. and Yan, C. and Hartley, S. L. and Handen, B. L. and Wisch, J. K. and Boehrwinkle, A. H. and Ances, B. M. and Rafii, M. S. and others},
title = {{Assessing amyloid PET positivity and cognitive function in Down syndrome to guide clinical trials targeting amyloid}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2024},
doi = {10.1002/alz.14068},
pmid = {38940611},
url = {https://doi.org/10.1002/alz.14068}
}
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