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Predicting Cognitive Decline in Amyloid-Positive Patients With Mild Cognitive Impairment or Mild Dementia
van der Veere PJ, Hoogland J, Visser LNC, Van Harten AC, Rhodius-Meester HF, Sikkes SAM, Venkatraghavan V, Barkhof F et al.. Neurology, 2024-07-10
Topic: Amyloid, tau and blood-test diagnosis
Background and objectives Cognitive decline rates in Alzheimer disease (AD) vary greatly. Disease-modifying treatments may alter cognitive decline trajectories, rendering their prediction increasingly relevant. We aimed to construct clinically applicable prediction models of cognitive decline in amyloid-positive patients with mild cognitive impairment (MCI) or mild dementia. Methods From the Amsterdam Dementia Cohort, we selected amyloid-positive participants with MCI or mild dementia and at least 2 longitudinal Mini-Mental State Examination (MMSE) measurements. Amyloid positivity was based on CSF AD biomarker concentrations or amyloid PET. We used linear mixed modeling to predict MMSE over time, describing trajectories using a cubic time curve and interactions between linear time and the baseline predictors age, sex, baseline MMSE, APOE ε4 dose, CSF β-amyloid (Aβ) 1-42 and pTau, and MRI total brain and hippocampal volume. Backward selection was used to reduce model complexity. These models can predict MMSE over follow-up or the time to an MMSE value. MCI and mild dementia were modeled separately. Internal 5-fold cross-validation was performed to calculate the explained variance ( R 2 ). Results In total, 961 participants were included (age 65 ± 7 years, 49% female), 310 had MCI (MMSE 26 ± 2) and 651 had mild dementia (MMSE 22 ± 4), with 4 ± 2 measurements over 2 (interquartile range 1-4) years. Cognitive decline rates increased over time for both MCI and mild dementia (model comparisons linear vs squared vs cubic time fit; p APOE ε4, and baseline MMSE. R 2 was 0.15 for the MCI model and 0.26 for mild dementia in internal cross-validation. A hypothetical patient with MCI, baseline MMSE 28, and CSF Aβ1-42 of 925 pg/mL was predicted to reach an MMSE of 20 after 6.0 years (95% CI 5.4-6.7) and after 8.6 years with a hypothetical treatment reducing decline by 30%. Discussion We constructed models for MCI and mild dementia that predict MMSE over time. These models could inform patients about their potential cognitive trajectory and the remaining uncertainty and aid in conversations about individualized potential treatment effects.
Key findings
- Results In total, 961 participants were included (age 65 ± 7 years, 49% female), 310 had MCI (MMSE 26 ± 2) and 651 had mild dementia (MMSE 22 ± 4), with 4 ± 2 measurements over 2 (interquartile range 1-4) years.
Why it matters
This study built models using data from 961 amyloid-positive participants with mild cognitive impairment or mild dementia to predict cognitive decline over time. It is a prediction modeling study and does not test any treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Study designlongitudinal study
- Participants961
- Evidence strengthModerate
How this study scored 63/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 961 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 | 3 / 7 | Cited 25 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.2 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 3 / 6 | Cited 6.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 25 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Wiesje M. van der Flier: h-index 132 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Amsterdam UMC Location Vrije Universiteit Amsterdam: institution h-index 938 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38986053) |
| Free to read | 2 / 2 | Free to read |
| Total | 63 / 100 | — |
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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
van der Veere, P. J., Hoogland, J., Visser, L. N. C., Van Harten, A. C., Rhodius-Meester, H. F., Sikkes, S. A. M., et al. (2024). Predicting Cognitive Decline in Amyloid-Positive Patients With Mild Cognitive Impairment or Mild Dementia. Neurology. https://doi.org/10.1212/wnl.0000000000209605
Vancouver
van der Veere PJ, Hoogland J, Visser LNC, Van Harten AC, Rhodius-Meester HF, Sikkes SAM, et al. Predicting Cognitive Decline in Amyloid-Positive Patients With Mild Cognitive Impairment or Mild Dementia. Neurology. 2024. doi:10.1212/wnl.0000000000209605. PMID: 38986053.
BibTeX
@article{vanderveere2024-38986053,
author = {van der Veere, P. J. and Hoogland, J. and Visser, L. N. C. and Van Harten, A. C. and Rhodius-Meester, H. F. and Sikkes, S. A. M. and Venkatraghavan, V. and Barkhof, F. and others},
title = {{Predicting Cognitive Decline in Amyloid-Positive Patients With Mild Cognitive Impairment or Mild Dementia}},
journal = {Neurology},
year = {2024},
doi = {10.1212/wnl.0000000000209605},
pmid = {38986053},
url = {https://doi.org/10.1212/wnl.0000000000209605}
}
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