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Record W4401750665 · doi:10.1101/2024.08.19.608305

An estimate of the longitudinal pace of aging from a single brain scan predicts dementia conversion, morbidity, and mortality

2024· preprint· en· W4401750665 on OpenAlexfundno aff
Ethan T. Whitman, Maxwell L. Elliott, Annchen R. Knodt, Wickliffe C. Abraham, Tim Anderson, Nick Cutfield, Sean Hogan, David Ireland, Tracy R. Melzer, Sandhya Ramrakha, Karen Sugden, Reremoana Theodore, Benjamin Williams, Avshalom Caspi, Terrie E. Moffitt, Ahmad R. Hariri

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldMedicine
TopicDementia and Cognitive Impairment Research
Canadian institutionsnot available
FundersHealth Research Council of New ZealandCanadian Institutes of Health ResearchNational Institutes of HealthGenentechIXICOH. Lundbeck A/SServierEisaiNorthern California Institute for Research and EducationPfizerNovartis Pharmaceuticals CorporationMedical Research CouncilBiogenEli Lilly and CompanyBristol-Myers SquibbBioClinicaAlzheimer's Disease Neuroimaging InitiativeMeso Scale DiagnosticsNational Institute on AgingAlzheimer's AssociationFoundation for the National Institutes of Health
KeywordsDementiaNeuroimagingBrain agingBiobankAlzheimer's Disease Neuroimaging InitiativeGerontologyLongitudinal studySuccessful agingAging brainMedicineAlzheimer's diseaseAtrophyBiomarkerHealthy agingCognitive declinePsychologyCognitionPhysical medicine and rehabilitationDiseaseNeuroscienceBioinformaticsInternal medicinePathologyBiology

Abstract

fetched live from OpenAlex

To understand how aging affects functional decline and increases disease risk, it is necessary to develop accurate and reliable measures of how fast a person is aging. Epigenetic clocks measure aging but require DNA methylation data, which many studies lack. Using data from the Dunedin Study, we introduce an accurate and reliable measure for the rate of longitudinal aging derived from cross-sectional brain MRI: the Dunedin Pace of Aging Calculated from NeuroImaging or DunedinPACNI. Exporting this measure to the Alzheimer's Disease Neuroimaging Initiative and UK Biobank datasets revealed that faster DunedinPACNI predicted participants' cognitive impairment, accelerated brain atrophy, and conversion to diagnosed dementia. Underscoring close links between longitudinal aging of the body and brain, faster DunedinPACNI also predicted physical frailty, poor health, future chronic diseases, and mortality in older adults. Furthermore, DunedinPACNI followed an established socioeconomic health gradient with people of lower socioeconomic status showing faster DunedinPACNI. Associations between DunedinPACNI and cognitive impairment were replicated in BrainLat, a sample of Latin American patients with dementia. When compared to brain age gap, an existing MRI aging biomarker, DunedinPACNI was similarly or more strongly related to clinical outcomes. DunedinPACNI is a "next generation" MRI measure that will be made publicly available to the research community to help accelerate aging research and evaluate the effectiveness of dementia prevention and anti-aging strategies.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.012
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.007
Threshold uncertainty score0.016

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.012
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.002
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.025
GPT teacher head0.294
Teacher spread0.268 · 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 source (direct Gemma or distilled Codex), 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

Citations1
Published2024
Admission routes1
Has abstractyes

Explore more

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