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Record W4406785651 · doi:10.1101/2025.01.22.25320988

Brain Age: A Promising Biomarker for Understanding Aging in the Context of Cognitive Reserve

2025· preprint· en· W4406785651 on OpenAlexaff
Iman Beheshti

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldComputer Science
TopicCognitive Science and Mapping
Canadian institutionsUniversity of Manitoba
FundersNational Institutes of HealthH. Lundbeck A/SBioClinicaU.S. Department of DefenseMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeBristol-Myers SquibbEli Lilly and CompanyBiogenEisaiAlzheimer's AssociationGenentechIXICO
KeywordsCognitive reserveContext (archaeology)BiomarkerCognitive agingCognitionBrain agingCognitive declineAging brainPsychologyHealthy agingNeuroscienceGerontologyMedicineCognitive impairmentGeographyDementiaBiologyInternal medicineDiseaseArchaeology

Abstract

fetched live from OpenAlex

ABSTRACT INTRODUCTION Cognitive decline is a major concern in aging populations. Detecting it before clinical symptoms emerge remains a significant challenge. A precise, reliable, and non-invasive biomarker for cognitive health could revolutionize how we monitor normal aging and lifestyle impacts. Such a tool would not only identify individuals at risk of cognitive decline years before symptoms manifest but also aid in early interventions and treatments. METHODS Longitudinal MRI data from 121 high cognitive reserve (HCR) individuals were compared to matched low cognitive reserve (LCR) individuals to evaluate four biomarkers for early cognitive decline and disease progression: brain age delta, cortical thickness, AD cortical signature, and hippocampal volume. Cross-sectional analyses were conducted at baseline, alongside longitudinal assessments spanning 1 to 12 years, to compare the performance and properties of these biomarkers. RESULTS The brain age metric emerged as the most reliable biomarker, demonstrating a significant ability to differentiate between groups at baseline ( β = 1.250, t = 3.521, p = 0.0009; linear regression model; AUC = 0.73). Furthermore, this biomarker maintained its robustness as the strongest predictor of group membership over a follow-up period of up to 12 years ( β = 0.409, p = 0.025; mixed-effects model), underscoring its potential for longitudinal monitoring of cognitive decline. DISCUSSION The brain age biomarker demonstrates potential as an effective indicator for early cognitive decline, capable of detecting changes years before clinical symptoms appear and tracking age-related brain and cognitive changes over time. These findings suggest that integrating MRI biomarkers with machine learning approaches could yield more accurate and reliable tools for assessing cognitive health, surpassing the limitations of relying solely on MRI biomarkers. Key Points Question: Which T1-weighted MRI biomarkers are most effective in predicting longitudinal cognitive deterioration in the aging population? Highlights Four commonly used MRI biomarkers were assessed in the context of cognitive aging. Brain age is validated as a promising biomarker for aging and cognitive reserve. Machine learning boosts cognitive biomarker accuracy beyond neuroimaging alone. The findings underscore a direct association between structural brain reserve and cognitive reserve. Key factors in brain preservation may support high cognitive reserve in aging.

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)0.003
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.908
Threshold uncertainty score0.662

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
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 head0.149
GPT teacher head0.357
Teacher spread0.208 · 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 designTheoretical or conceptual
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

Citations2
Published2025
Admission routes1
Has abstractyes

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