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Functional assessment improves discrimination of clinical and biomarker-defined Alzheimer’s disease
Mavromati K, Dibble AJ, Tvrda L, Dalby C, Beazer JD, Hughes L, Kennelly SP, Quinn TJ.. medRxiv, 2026-07-31
Topic: Brain imaging, connectivity and assessment
INTRODUCTION Accurately identifying risk of Alzheimer’s Dementia (AD) is essential for supporting people living with symptoms in clinical settings, as well as recruiting adults in prospective medical research. Various algorithms have been created to calculate AD risk based on evidenced risk factors which are weighted toward a total score. As daily life conditions determining risk change at scale, it remains unclear how effective gold standard algorithms remain in modern cohorts. METHODS In the Bio-Hermes-001 diverse cohort, we assessed algorithm discrimination and calibration in six outcomes: classifying AB PET binary outcome (negative N = 603, positive N = 342); phosphorylated tau-217 binary outcome (pTau-217 negative N = 166, positive N = 469); participants with Healthy Cognition (N = 417) from probable AD (N = 272); HC from Mild Cognitive Impairment (N = 312), HC from pooled MCI or AD; and MCI from AD. Approximately a third of the cohort are individuals from populations typically underrepresented in dementia research (HC: 19%; MCI: 24%; AD: 33%). RESULTS Hosmer-Lemeshow tests and Brier score demonstrate acceptable calibration of all algorithms except the oldest algorithm. However, Receiver Operating Characteristic (ROC) curves and the associated area under the curve (AUC) estimates evidenced that in this cohort only the BDSI exceeded conventional thresholds for good discrimination (.8 AUC in HC-AD classification, with AUC approximately .7 in the other clinical, AB PET, and pTau-217 comparisons). When the functional item is removed from the BDSI score, it remains acceptably calibrated, but DeLong tests reflect statistically significant reduction in discriminatory performance for all group comparisons. The two earliest published algorithms were only chance-level accurate. DISCUSSION In a contemporary, diverse cohort, most established dementia risk algorithms had limited power in discriminating amyloid positivity, pTau-217 positivity, and current cognitive status despite acceptable calibration. Including a functional measure markedly improved discrimination across both clinical and biomarker-defined outcomes, suggesting that proximal indicators of cognitive vulnerability are critical for identifying individuals with underlying AD-related pathology.
Key findings
- RESULTS Hosmer-Lemeshow tests and Brier score demonstrate acceptable calibration of all algorithms except the oldest algorithm.
- When the functional item is removed from the BDSI score, it remains acceptably calibrated, but DeLong tests reflect statistically significant reduction in discriminatory performance for all group comparisons.
- Including a functional measure markedly improved discrimination across both clinical and biomarker-defined outcomes, suggesting that proximal indicators of cognitive vulnerability are critical for identifying individuals with underlying AD-related pathology.
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Study details
- Participants603
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 35 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, effect reported and randomised / 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 multi-centre collaboration, so those were left out: it earned 22 of the 62 points we could judge it on, which is 35 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 | 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 | 2 / 4 | 603 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 | — / 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 |
| Multi-centre 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 | 2 / 2 | Free to read |
| Points | 22 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 22 of the 62 points we could judge it on is 35 out of 100. |
| Total | 35 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Mavromati, K., Dibble, A. J., Tvrda, L., Dalby, C., Beazer, J. D., Hughes, L., et al. (2026). Functional assessment improves discrimination of clinical and biomarker-defined Alzheimer’s disease. medRxiv. https://doi.org/10.64898/2026.07.29.26359236
Vancouver
Mavromati K, Dibble AJ, Tvrda L, Dalby C, Beazer JD, Hughes L, et al. Functional assessment improves discrimination of clinical and biomarker-defined Alzheimer’s disease. medRxiv. 2026. doi:10.64898/2026.07.29.26359236.
BibTeX
@article{mavromati2026-eee5059c,
author = {Mavromati, K. and Dibble, A. J. and Tvrda, L. and Dalby, C. and Beazer, J. D. and Hughes, L. and Kennelly, S. P. and Quinn, T. J.},
title = {{Functional assessment improves discrimination of clinical and biomarker-defined Alzheimer’s disease}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.07.29.26359236},
url = {https://doi.org/10.64898/2026.07.29.26359236}
}
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