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Record W4413291038 · doi:10.1002/hbm.70276

Mind the Gap: Does Brain Age Improve Alzheimer’s Disease Prediction?

2025· article· en· W4413291038 on OpenAlexfundno aff
Trevor Wei Kiat Tan, Kim‐Ngan Nguyen, Chen Zhang, Ru Kong, Susan F Cheng, Fang Ji, Joanna Su Xian Chong, Eddie Chong, Narayanaswamy Venketasubramanian, Csaba Orbán, Michael W.L. Chee, Christopher Chen, Juan Zhou, B.T. Thomas Yeo

Bibliographic record

VenueHuman Brain Mapping · 2025
Typearticle
Languageen
FieldMedicine
TopicDementia and Cognitive Impairment Research
Canadian institutionsnot available
FundersNational Institute of Mental HealthNational Medical Research CouncilCanadian Institutes of Health ResearchNational Institutes of HealthGenentechIXICOH. Lundbeck A/SServierEisaiNorthern California Institute for Research and EducationMinistry of Health -SingaporeBioClinicaBiogenPfizerNovartis Pharmaceuticals CorporationUniversity of Southern CaliforniaMeso Scale DiagnosticsMedical Research CouncilU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbAlzheimer's Disease Neuroimaging InitiativeNational Institute on AgingAlzheimer's Association
KeywordsDementiaBrain agingDiseaseMachine learningPsychologyArtificial intelligenceComputer scienceCognitive psychologyNeuroscienceMedicineCognitionPathology

Abstract

fetched live from OpenAlex

Brain age is widely regarded as a powerful marker of general brain health. Brain age models are typically trained on large datasets to predict chronological age, which may offer advantages in predicting specific health outcomes, much like the success of finetuning large language models for specific applications. However, it is also well accepted that machine learning models trained to directly predict specific outcomes (i.e., direct models) often outperform those trained on surrogate objectives. Therefore, despite their much larger training data, it is unclear whether brain age models outperform direct models in predicting specific brain health outcomes. Here, we compare large-scale brain age models (pretrained on 53,542 participants) and direct models for predicting specific health outcomes related to Alzheimer's disease (AD) dementia. Using anatomical T1 scans from three continents (N = 1,848), we find that summarizing brain age with a single scalar (i.e., brain age gap) led to poor prediction performance. Using higher-dimensional intermediate representations of brain age models led to better prediction, but was still worse than direct models without finetuning. Using intermediate representations of finetuned brain age models was necessary to achieve similar performance to direct models. Overall, our results do not discount brain age as a useful marker of general brain health but suggest that using chronological age as a pretraining target might be suboptimal for predicting specific health outcomes.

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.

How this classification was reachedexpand

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.568
Threshold uncertainty score0.772

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.038
GPT teacher head0.342
Teacher spread0.304 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations5
Published2025
Admission routes1
Has abstractyes

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