Predicting rates of cognitive and functional decline in Alzheimer’s disease and mild cognitive impairment
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
The global population of People Living with Dementia (PLWD) is expected to grow rapidly in the coming decades, increasing the need for personalised, generalisable, and scalable prognosis and care planning support. However, current prognostic guidance does not adequately capture the heterogeneity in dementia trajectories, and existing predictive models of dementia progression rely on costly and inaccessible data, limiting their scalability in resource-constrained settings.
Methods
Using clinical assessments, demographic, and medical history data from 153 12-month clinical trajectories collected over three years, two machine learning algorithms were developed to predict 12-month cognitive and functional decline in Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI). Models were externally validated on 741 trajectories from the ADNI cohort. Cognitive and functional decline were estimated using the Mini-Mental State Exam (MMSE) and Bristol Activities of Daily Living (BADL).
Results
The MMSE model achieves a mean absolute error (MAE) of 1.84 (95% CI: 1.64-2.04) internally and 2.19 in external validation. The BADL model achieves an MAE of 3.88 (95% CI: 3.46-4.30). Baseline scores on ideational praxis, orientation, and word recall are among the strongest predictors of cognitive decline, while independence in food preparation, finances, and dressing are among the top predictors of functional decline.
Conclusions
Our models use only routinely collected and easily accessible data, offering high translational potential. If implemented, our scalable, data-driven prognostic support tool could streamline clinical workflows, support personalised care planning, and provide PLWD and their families with greater clarity and reassurance.
The global population of People Living with Dementia (PLWD) is expected to grow rapidly in the coming decades, increasing the need for personalised, generalisable, and scalable prognosis and care planning support. However, current prognostic guidance does not adequately capture the heterogeneity in dementia trajectories, and existing predictive models of dementia progression rely on costly and inaccessible data, limiting their scalability in resource-constrained settings.
Methods
Using clinical assessments, demographic, and medical history data from 153 12-month clinical trajectories collected over three years, two machine learning algorithms were developed to predict 12-month cognitive and functional decline in Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI). Models were externally validated on 741 trajectories from the ADNI cohort. Cognitive and functional decline were estimated using the Mini-Mental State Exam (MMSE) and Bristol Activities of Daily Living (BADL).
Results
The MMSE model achieves a mean absolute error (MAE) of 1.84 (95% CI: 1.64-2.04) internally and 2.19 in external validation. The BADL model achieves an MAE of 3.88 (95% CI: 3.46-4.30). Baseline scores on ideational praxis, orientation, and word recall are among the strongest predictors of cognitive decline, while independence in food preparation, finances, and dressing are among the top predictors of functional decline.
Conclusions
Our models use only routinely collected and easily accessible data, offering high translational potential. If implemented, our scalable, data-driven prognostic support tool could streamline clinical workflows, support personalised care planning, and provide PLWD and their families with greater clarity and reassurance.
Date Issued
2026-04-08
Date Acceptance
2026-02-02
Citation
Communications Medicine, 2026, 6
ISSN
2730-664X
Publisher
Nature Portfolio
Journal / Book Title
Communications Medicine
Volume
6
Copyright Statement
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1038/s43856-026-01432-w
Publication Status
Published
Article Number
ARTN 193
Date Publish Online
2026-02-26