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Accelerated functional brain aging in pre-clinical familial Alzheimer’s disease
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Bibliographic record
VenueNature Communications · 2021
Typearticle
Languageen
FieldNeuroscience
TopicFunctional Brain Connectivity Studies
Canadian institutionsUniversité de MontréalInstitut Universitaire de Gériatrie de MontréalSt Joseph's Health CentreMcGill University Health CentreUniversity of British Columbia HospitalSunnybrook Health Science CentreMcGill UniversityDouglas Mental Health University InstituteSt Joseph's Health CareMontreal Neurological Institute and Hospital
FundersNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchPfizer CanadaGenentechNational Institutes of HealthFleniIXICOServierH. Lundbeck A/SDeutsches Zentrum für Neurodegenerative ErkrankungenEisaiCanada Research ChairsGovernment of CanadaRéseau en Bio-Imagerie du QuebecKorea Health Industry Development InstituteNorthern California Institute for Research and EducationJapan Agency for Medical Research and DevelopmentMcGill UniversityFondation Brain CanadaPfizerBiogenBioClinicaF. Hoffmann-La RocheUniversity of Southern CaliforniaEli Lilly and CompanyU.S. Department of DefenseMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeNovartis Pharmaceuticals CorporationAlzheimer SocietyBristol-Myers SquibbAlzheimer's AssociationFoundation for the National Institutes of Health
KeywordsDementiaContext (archaeology)Brain agingNeuroscienceDiseaseAlzheimer's diseaseResting state fMRIFunctional connectivityMedicineNeuroimagingPsychologyBiologyPathology
Abstract
Resting state functional connectivity (rs-fMRI) is impaired early in persons who subsequently develop Alzheimer's disease (AD) dementia. This impairment may be leveraged to aid investigation of the pre-clinical phase of AD. We developed a model that predicts brain age from resting state (rs)-fMRI data, and assessed whether genetic determinants of AD, as well as beta-amyloid (Aβ) pathology, can accelerate brain aging. Using data from 1340 cognitively unimpaired participants between 18-94 years of age from multiple sites, we showed that topological properties of graphs constructed from rs-fMRI can predict chronological age across the lifespan. Application of our predictive model to the context of pre-clinical AD revealed that the pre-symptomatic phase of autosomal dominant AD includes acceleration of functional brain aging. This association was stronger in individuals having significant Aβ pathology.
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 imitationNot 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)0.000
metaresearch head score (Gemma)0.030
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.609
Threshold uncertainty score0.978
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.030 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 head0.174
GPT teacher head0.402
Teacher spread0.228 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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
Citations100
Published2021
Admission routes2
Has abstractyes