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Sensitivity comparison of longitudinal cognitive function indicators of Alzheimer’s disease after mild cognitive impairment: a prospective cohort study
Guiya Guo, Wangchen Song, Aimin Wang, Qingxia Cui, Xinyu Yang, Yanxia Wang, Yonghua Ma, Hairui Han et al.. Scientific Reports, 2026-03-22
Topic: Amyloid, tau and blood-test diagnosis
Accurate prediction of progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is critical for early intervention. Many existing models lack the ability to capture the nonlinear nature of cognitive decline and individual heterogeneity. This study employed a semi‑parametric joint model to analyze longitudinal cognitive trajectories and identify robust predictors of conversion. Data from 596 participants (184 AD converters, 412 stable MCI) were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Longitudinal assessments included ADAS‑Cog13, ADAS‑Cog11, CDR‑SB, FAQ, RAVLT‑IR, RAVLT‑L, and MMSE. A semi‑parametric joint model combining B‑splines for the longitudinal process with a Cox survival submodel was fitted for each cognitive measure. Model performance was evaluated using AIC, BIC, intraclass correlation coefficient (ICC), time‑dependent C‑index, dynamic AUC, and calibration curves. Subgroup analyses were conducted by APOE‑ε4 carrier status. In multivariable joint models, APOE‑ε4 carriage was a consistent risk factor (HR range: 1.38-1.77). Higher scores on ADAS‑Cog13 (HR = 3.71 per SD), ADAS‑Cog11 (HR = 2.71), CDR‑SB (HR = 3.79), and FAQ (HR = 2.85) increased the hazard of conversion, whereas higher scores on RAVLT‑IR (HR = 0.23), RAVLT‑L (HR = 0.14), and MMSE (HR = 0.53) were protective. All models showed high ICCs (0.94-0.98) and moderate‑to‑good predictive accuracy over 2, 5, and 8 year horizons (C‑index: 0.585-0.668). CDR‑SB and FAQ exhibited the strongest effect sizes and clearest dose‑dependent trajectories across APOE‑ε4 subgroups. Calibration curves demonstrated good agreement between predicted and observed survival. The semi‑parametric joint model effectively captures nonlinear cognitive‑functional decline and provides validated predictions of AD risk. APOE‑ε4 genotype combined with longitudinal monitoring of CDR‑SB and FAQ offers a robust framework for stratifying progression risk in clinical MCI management.
Key findings
- Calibration curves demonstrated good agreement between predicted and observed survival.
Why it matters
This study found that higher scores on ADAS-Cog13, ADAS-Cog11, CDR-SB, and FAQ increased the hazard of conversion from mild cognitive impairment to Alzheimer's disease, while higher RAVLT-IR, RAVLT-L, and MMSE scores were protective, and APOE-ε4 carriage was a consistent risk factor. It does not test a treatment or cure, but it suggests certain cognitive measures may help predict who will convert.
Study details
- Study designlongitudinal study
- Participants596
- Effect sizeHR = 3.71; HR = 2.71; HR = 3.79
- Evidence strengthModerate
How this study scored 53/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for randomised / blinded because the record does not state it. We have no data on institution's track record, so that was left out: it earned 51 of the 97 points we could judge it on, which is 53 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Scientific Reports) |
| Journal's citation record | 3 / 4 | Scientific Reports: journal h-index 463 (OpenAlex, 2026-10-29) |
| 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 | 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 | 2 / 4 | 596 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.7× 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 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 0 / 4 | Last-listed author Fuyan Shi: h-index 3 (OpenAlex, whole career) |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 0 institution(s) in 0 countries — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41866365) |
| Free to read | 2 / 2 | Free to read |
| Points | 51 / 97 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 51 of the 97 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
- DOI: 10.1038/s41598-026-44192-2
- PubMed: 41866365
- Original source →
- Free full text: Scientific Reports →
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
Guo, G., Song, W., Wang, A., Cui, Q., Yang, X., Wang, Y., et al. (2026). Sensitivity comparison of longitudinal cognitive function indicators of Alzheimer’s disease after mild cognitive impairment: a prospective cohort study. Scientific Reports. https://doi.org/10.1038/s41598-026-44192-2
Vancouver
Guo G, Song W, Wang A, Cui Q, Yang X, Wang Y, et al. Sensitivity comparison of longitudinal cognitive function indicators of Alzheimer’s disease after mild cognitive impairment: a prospective cohort study. Scientific Reports. 2026. doi:10.1038/s41598-026-44192-2. PMID: 41866365.
BibTeX
@article{guo2026-41866365,
author = {Guo, Guiya and Song, Wangchen and Wang, Aimin and Cui, Qingxia and Yang, Xinyu and Wang, Yanxia and Ma, Yonghua and Han, Hairui and others},
title = {{Sensitivity comparison of longitudinal cognitive function indicators of Alzheimer’s disease after mild cognitive impairment: a prospective cohort study}},
journal = {Scientific Reports},
year = {2026},
doi = {10.1038/s41598-026-44192-2},
pmid = {41866365},
url = {https://doi.org/10.1038/s41598-026-44192-2}
}
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