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A digital biomarker of white-matter routing from diffusion MRI as an early biomarker of Alzheimer’s disease
Ghodrat M, Schlachetzki JC, the Alzheimer’s Disease Neuroimaging Initiative.. medRxiv, 2026-10-24
Topic: Brain imaging, connectivity and assessment
Alzheimer’s disease is diagnosed after a decade-long phase in which pathology accumulates; current markers show that pathology is present, but not how far it has advanced. Because white-matter structure is altered early, we computed two graph-theoretic indices of periventricular white-matter routing from diffusion MRI in 1,706 OASIS-3 sessions: the Route Concordance Index (RCI), a population-calibrated path-concordance score over 316 routes, and a global conductance from the connectome’s graph Laplacian. RCI was reduced before clinical conversion and declined monotonically across a five-stage trajectory (cross-validated AUC = 0.817 for stable-CN vs. pre-AD; comparable to hippocampal volume and exceeding entorhinal thickness, global conductance, and DTI-ALPS), with degradation concentrated in fronto-striatal circuits. A classifier combining these routing features with demographic, structural-MRI and cognitive covariates detected conversion to MCI or AD up to four years before diagnosis (AUC = 0.831; 0.918 within one year; modest positive predictive value). Findings replicated in ADNI ( n = 609; conductance AUC = 0.805; RCI = 0.797 under frozen external validation) and tracked CSF amyloid- β 42 in the expected direction. Computed from a standard diffusion MRI sequence, RCI is comparable to established structural and demographic biomarkers on preclinical discrimination while, unlike them, declining cleanly and monotonically across the disease trajectory, supporting prospective validation for risk stratification.
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APA 7th
Ghodrat, M., Schlachetzki, J. C., & the Alzheimer’s Disease Neuroimaging Initiative. (2026). A digital biomarker of white-matter routing from diffusion MRI as an early biomarker of Alzheimer’s disease. medRxiv. https://doi.org/10.64898/2026.10.21.26366165
Vancouver
Ghodrat M, Schlachetzki JC, the Alzheimer’s Disease Neuroimaging Initiative. A digital biomarker of white-matter routing from diffusion MRI as an early biomarker of Alzheimer’s disease. medRxiv. 2026. doi:10.64898/2026.10.21.26366165.
BibTeX
@article{ghodrat2026-717b639d,
author = {Ghodrat, M. and Schlachetzki, J. C. and {the Alzheimer’s Disease Neuroimaging Initiative}},
title = {{A digital biomarker of white-matter routing from diffusion MRI as an early biomarker of Alzheimer’s disease}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.10.21.26366165},
url = {https://doi.org/10.64898/2026.10.21.26366165}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Because white-matter structure is altered early, we computed two graph-theoretic indices of periventricular white-matter routing from diffusion MRI in 1,706 OASIS-3 sessions: the Route Concordance Index (RCI), a population-calibrated path-concordance score over 316 routes, and a global conductance from the connectome’s graph Laplacian.
- RCI was reduced before clinical conversion and declined monotonically across a five-stage trajectory (cross-validated AUC = 0.817 for stable-CN vs. pre-AD; comparable to hippocampal volume and exceeding entorhinal thickness, global conductance, and DTI-ALPS), with degradation concentrated in fronto-striatal circuits.
- A classifier combining these routing features with demographic, structural-MRI and cognitive covariates detected conversion to MCI or AD up to four years before diagnosis (AUC = 0.831; 0.918 within one year; modest positive predictive value).
- Findings replicated in ADNI ( n = 609; conductance AUC = 0.805; RCI = 0.797 under frozen external validation) and tracked CSF amyloid- β 42 in the expected direction.
- Computed from a standard diffusion MRI sequence, RCI is comparable to established structural and demographic biomarkers on preclinical discrimination while, unlike them, declining cleanly and monotonically across the disease trajectory, supporting prospective validation for risk stratification.
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Study details
- Participants609
- Effect sizeAUC = 0.817; AUC = 0.831; AUC = 0.805
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 34 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design and randomized / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 21 of the 62 points we could judge it on, which is 34 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 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 | 2 / 4 | 609 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| 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 | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 21 of the 62 points we could judge it on is 34 out of 100. |
| Total | 34 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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