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MMSE–CDR‐SB residual as an exploratory indicator of deviation from an Alzheimer's disease–typical cognitive–functional pattern
Ambre Mounié, Kenichiro Sato, Saki Nakashima, Masanori Kurihara, Ryoko Ihara, Yoshiki Niimi, Atsushi Iwata, Takeshi Iwatsubo. Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, 2026-07-01
Topic: Amyloid, tau and blood-test diagnosis
Abstract INTRODUCTION In clinical practice, patients with Alzheimer's disease (AD) often present with cognitive and functional profiles that diverge from what is expected. We tested whether the Mini‐Mental State Examination Clinical Dementia Rating Sum of Boxes (MMSE–CDR‐SB) residual, defined as observed minus expected CDR‐SB from a published MMSE–CDR‐SB reference equation, reflects clinically meaningful deviation from the expected cognitive–functional relationship. METHODS Using National Alzheimer's Coordinating Center data, we analyzed an autopsy cohort ( n = 1981) and a separate clinical diagnosis cohort ( n = 3184). Negative residual values indicated less functional impairment than expected for a given cognitive score, and positive values indicated greater functional impairment than expected. Associations were examined using multivariable logistic regression adjusted for MMSE score range, age, sex, and education. RESULTS Lower residual values were associated with lower odds of amyloid and AD‐type tau pathology. Higher residual values showed a directional association with transactive response DNA binding protein 43 kDa; vascular burden was also associated with the residual index but across a broader range. In the clinical cohort, higher residual values were enriched in progressive supranuclear palsy and frontotemporal lobar degeneration (other), whereas AD cases clustered near the reference pattern. DISCUSSION The MMSE–CDR‐SB residual may help flag less AD‐typical presentations for further etiologic evaluation, but cannot be interpreted as a pathology‐specific marker due to substantial overlap across diagnostic groups.
Key findings
- RESULTS Lower residual values were associated with lower odds of amyloid and AD‐type tau pathology.
- Higher residual values showed a directional association with transactive response DNA binding protein 43 kDa; vascular burden was also associated with the residual index but across a broader range.
Why it matters
A measure called the MMSE–CDR-SB residual, based on how much a person's daily functioning differs from what their cognitive score would predict, was linked to different underlying brain pathologies at autopsy. This is an exploratory diagnostic indicator and does not test any treatment or prevention.
Study details
- Participants1,981
- Evidence strengthModerate
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring) |
| Journal's citation record | 1 / 4 | Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring: journal h-index 86 (OpenAlex, 2026-10-29) |
| 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 | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,981 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 | 0 / 6 | Cited 0.0× the average for papers of its field and year (OpenAlex FWCI) |
| 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 | 4 / 4 | Last-listed author Takeshi Iwatsubo: h-index 115 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | The University of Tokyo: institution h-index 1,463 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42657316) |
| Free to read | 2 / 2 | Free to read |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1002/dad2.70460
- PubMed: 42657316
- Original source →
- Free full text: Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring →
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 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
Mounié, A., Sato, K., Nakashima, S., Kurihara, M., Ihara, R., Niimi, Y., et al. (2026). MMSE–CDR‐SB residual as an exploratory indicator of deviation from an Alzheimer's disease–typical cognitive–functional pattern. Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring. https://doi.org/10.1002/dad2.70460
Vancouver
Mounié A, Sato K, Nakashima S, Kurihara M, Ihara R, Niimi Y, et al. MMSE–CDR‐SB residual as an exploratory indicator of deviation from an Alzheimer's disease–typical cognitive–functional pattern. Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring. 2026. doi:10.1002/dad2.70460. PMID: 42657316.
BibTeX
@article{mounie2026-42657316,
author = {Mounié, Ambre and Sato, Kenichiro and Nakashima, Saki and Kurihara, Masanori and Ihara, Ryoko and Niimi, Yoshiki and Iwata, Atsushi and Iwatsubo, Takeshi},
title = {{MMSE–CDR‐SB residual as an exploratory indicator of deviation from an Alzheimer's disease–typical cognitive–functional pattern}},
journal = {Alzheimer s \& Dementia Diagnosis Assessment \& Disease Monitoring},
year = {2026},
doi = {10.1002/dad2.70460},
pmid = {42657316},
url = {https://doi.org/10.1002/dad2.70460}
}
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