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Record W4413187029 · doi:10.1093/biomethods/bpaf051

An explainable AI approach for mapping multivariate regional brain age and clinical severity patterns in Alzheimer’s disease

2025· article· en· W4413187029 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueBiology Methods and Protocols · 2025
Typearticle
Languageen
FieldComputer Science
TopicMachine Learning in Healthcare
Canadian institutionsnot available
FundersCanadian Institutes of Health ResearchNational Institutes of HealthGenentechIXICOServierEisaiPfizerNovartis Pharmaceuticals CorporationH. Lundbeck A/SWashington University in St. LouisBiogenBioClinicaEli Lilly and CompanyBristol-Myers SquibbU.S. Department of DefenseMeso Scale DiagnosticsNational Institute on AgingAlzheimer's AssociationMallinckrodt Institute of Radiology, School of Medicine, Washington University in St. Louis
KeywordsMultivariate statisticsMultivariate analysisDiseasePsychologyGerontologyMedicineInternal medicineComputer scienceMachine learning

Abstract

fetched live from OpenAlex

Abstract Age is a significant risk factor for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and identifying brain age patterns is critical for comprehending the normal aging and MCI/AD processes. Prior studies have widely established the univariate relationships between brain regions and age, while multivariate associations remain largely unexplored. Herein, various artificial intelligence (AI) models were used to perform brain age prediction using an MRI dataset (n = 825). The optimal AI model was then integrated with the feature importance methods, namely Shapley additive explanations (SHAP), local interpretable model-agnostic explanations, and layer-wise relevance propagation, to identify the significant multivariate brain regions hierarchically involved in this prediction. Our results showed that the deep learning model (referred to as AgeNet) outperformed conventional machine learning models for brain age prediction, and that AgeNet integrated with SHAP (referred to as AgeNet-SHAP) identified all ground-truth perturbed regions as key predictors of brain age in semi-simulation, demonstrating the validity of our methodology. In the experimental dataset, when compared to cognitively normal (CN) participants, MCI exhibited moderate differences in brain regions, whereas AD showed highly robust and widely distributed regional differences. Individualized AgeNet-SHAP regional features further showed associations with clinical severity scores in the AD continuum. These results collectively facilitate data-driven explainable AI approaches for disease progression, diagnostics, prognostics, and personalized medicine efforts.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.005
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.442
Threshold uncertainty score0.531

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0050.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.198
GPT teacher head0.549
Teacher spread0.351 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it