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Data-driven subtypes of Alzheimer's Disease: A multicohort study
Metz, A.; Polizzi, C.; Moqadam, R.; Chadwick, K.; Tremblay, C.; Chen, Z.; Zeighami, Y.; Villeneuve et al.. medRxiv (preprint), 2026-09-11
Topic: Amyloid, tau and blood-test diagnosis
INTRODUCTIONIndividuals with Alzheimers disease (AD) exhibit substantial heterogeneity in the severity of vascular changes and neurodegeneration, making the identification of biologically meaningful subtypes across the AD spectrum critical for improving prognosis and tailoring interventions. We aimed to determine whether data-driven subtyping of individuals at risk for or diagnosed with AD, based on magnetic resonance imaging (MRI), can identify distinct trajectories of disease progression and clinical outcomes. METHODSWe analyzed baseline biomarkers and longitudinal clinical and cognitive assessments from the PREVENT-AD, CIMA-Q, ALLFTD, and ADNI cohorts, including 1396 participants. Regional atrophy and White Matter Hyperintensity (WMH) burden were derived from T1-weighted MRI. The SuStaIn algorithm was applied to baseline data to infer individuals subtypes and stages based on MRI biomarker profiles. The resulting subtypes were compared in terms of baseline molecular biomarker levels and vascular risk factors, longitudinal cognitive decline trajectories, and clinical and neuropathological outcomes. RESULTSTwo distinct subtypes were identified across all cohorts: one characterized by early parahippocampal and cortical atrophy, and a second by initially elevated WMH volumes. Both subtypes showed abnormal tau and amyloid levels in- and ex-vivo, and subtype two exhibited increased vascular risk factors. Longitudinally, the atrophy-first subtype exhibited steeper cognitive decline than the WMH-first subtype. Accordingly, the atrophy-first subtype carried a higher risk of conversion to AD than the WMH-first group. DISCUSSIONThese findings, replicated in four diverse and independent datasets, support imaging-based subtyping as a scalable and clinically translatable approach for capturing heterogeneity in AD pathophysiology and associated cognitive trajectories.
Key findings
- Accordingly, the atrophy-first subtype carried a higher risk of conversion to AD than the WMH-first group.
Why it matters
This multicohort study identified two data-driven subtypes of Alzheimer's disease based on MRI: one with early atrophy and one with initially elevated white matter hyperintensity volumes. The atrophy-first subtype had a higher risk of conversion to Alzheimer's disease, but this is about subtyping and prognosis, not treatment, cure, or prevention.
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Study details
- Study designlongitudinal study
- Participants1,396
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 37 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 35 of the 94 points we could judge it on, which is 37 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv (preprint)) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,396 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| 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 | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Mahsa Dadar: h-index 40 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | McGill University: institution h-index 1,373 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 35 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 35 of the 94 points we could judge it on is 37 out of 100. |
| Total | 37 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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
Metz, A., Polizzi, C., Moqadam, R., Chadwick, K., Tremblay, C., Chen, Z., et al. (2026). Data-driven subtypes of Alzheimer's Disease: A multicohort study. medRxiv (preprint). https://doi.org/10.64898/2026.09.09.26362683
Vancouver
Metz A, Polizzi C, Moqadam R, Chadwick K, Tremblay C, Chen Z, et al. Data-driven subtypes of Alzheimer's Disease: A multicohort study. medRxiv (preprint). 2026. doi:10.64898/2026.09.09.26362683.
BibTeX
@article{metz2026-3850ee0d,
author = {Metz, A. and Polizzi, C. and Moqadam, R. and Chadwick, K. and Tremblay, C. and Chen, Z. and Zeighami, Y. and Villeneuve and others},
title = {{Data-driven subtypes of Alzheimer's Disease: A multicohort study}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.09.09.26362683},
url = {https://doi.org/10.64898/2026.09.09.26362683}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 15.