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Analyzing heterogeneity in Alzheimer disease using multimodal normative modeling on imaging‐based ATN biomarkers
Sayantan Kumar, Tom Earnest, Braden Yang, Deydeep Kothapalli, Andrew J. Aschenbrenner, Jason J. Hassenstab, Chengie Xiong, Beau M. Ances et al.. Alzheimer s & Dementia, 2025-04-01
Topic: Amyloid, tau and blood-test diagnosis
Greater intra-group heterogeneity in ATN abnormality patterns was observed in more severe clinical stages of AD. Higher DSI was associated with worse cognitive function and increased risk of disease progression. Subject-specific abnormality maps across ATN reveal the heterogeneous impact of AD on the brain. HIGHLIGHTS: Normative modeling examined AD heterogeneity across multimodal imaging biomarkers. Heterogeneity in spatial patterns of gray matter atrophy, amyloid, and tau burden. Higher within-group heterogeneity for AD patients at advanced dementia stages. Patient-specific metric summarized extent of neurodegeneration and neuropathology. Metric is a marker of poor brain health and can monitor risk of disease progression.
Key findings
- Greater intra-group heterogeneity in ATN abnormality patterns was observed in more severe clinical stages of AD.
- Higher DSI was associated with worse cognitive function and increased risk of disease progression.
- Subject-specific abnormality maps across ATN reveal the heterogeneous impact of AD on the brain.
- HIGHLIGHTS: Normative modeling examined AD heterogeneity across multimodal imaging biomarkers.
- Heterogeneity in spatial patterns of gray matter atrophy, amyloid, and tau burden.
Why it matters
This study found that abnormalities in amyloid, tau, and neurodegeneration imaging markers were more varied among patients at more severe stages of Alzheimer's disease. A patient-specific measure of these abnormalities was linked to worse cognitive function and increased risk of disease progression.
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Study details
- Study designcross-sectional
- Participants665
- Evidence strengthLow
How this study scored 53/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 51 of the 96 points we could judge it on, which is 53 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| 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 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 665 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 | 3 / 7 | Cited 17 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 9.5× 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 | 2 / 4 | Cited 17 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre 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 39010871) |
| Free to read | 2 / 2 | Free to read |
| Points | 51 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 51 of the 96 points we could judge it on is 53 out of 100. |
| Total | 53 / 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).
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
Kumar, S., Earnest, T., Yang, B., Kothapalli, D., Aschenbrenner, A. J., Hassenstab, J. J., et al. (2025). Analyzing heterogeneity in Alzheimer disease using multimodal normative modeling on imaging‐based ATN biomarkers. Alzheimer s & Dementia. https://doi.org/10.1002/alz.70143
Vancouver
Kumar S, Earnest T, Yang B, Kothapalli D, Aschenbrenner AJ, Hassenstab JJ, et al. Analyzing heterogeneity in Alzheimer disease using multimodal normative modeling on imaging‐based ATN biomarkers. Alzheimer s & Dementia. 2025. doi:10.1002/alz.70143. PMID: 39010871.
BibTeX
@article{kumar2025-39010871,
author = {Kumar, Sayantan and Earnest, Tom and Yang, Braden and Kothapalli, Deydeep and Aschenbrenner, Andrew J. and Hassenstab, Jason J. and Xiong, Chengie and Ances, Beau M. and others},
title = {{Analyzing heterogeneity in Alzheimer disease using multimodal normative modeling on imaging‐based ATN biomarkers}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz.70143},
pmid = {39010871},
url = {https://doi.org/10.1002/alz.70143}
}
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