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Defining overlooked structures reveals new associations between cortex and cognition in aging and Alzheimer's disease

2024· article· en· W4391991650 on OpenAlexfundno aff
Samira A. Maboudian, Ethan H. Willbrand, William J. Jagust, Kevin S. Weiner

Bibliographic record

VenueJournal of Neuroscience · 2024
Typearticle
Languageen
FieldNeuroscience
TopicFunctional Brain Connectivity Studies
Canadian institutionsnot available
FundersNational Institutes of HealthGenentechNational Institute of Neurological Disorders and StrokeIXICONational Institute of General Medical SciencesH. Lundbeck A/SServierEisaiNorthern California Institute for Research and EducationPfizerBiogenBioClinicaMcDonnell Center for Systems NeuroscienceF. Hoffmann-La RocheUniversity of Southern CaliforniaMeso Scale DiagnosticsEli Lilly and CompanyU.S. Department of DefenseAlzheimer's Disease Neuroimaging InitiativeBristol-Myers SquibbNational Institute on AgingAlzheimer's AssociationCanadian Institutes of Health ResearchNational Science Foundation
KeywordsAtrophyCognitionBrain agingNeurosciencePsychologyHuman brainCortex (anatomy)Cerebral cortexCognitive declineDiseaseDementiaMedicinePathology

Abstract

fetched live from OpenAlex

Recent work suggests that indentations of the cerebral cortex, or sulci, may be uniquely vulnerable to atrophy in aging and Alzheimer's disease (AD) and that posteromedial cortex (PMC) is particularly vulnerable to atrophy and pathology accumulation. However, these studies did not consider small, shallow, and variable tertiary sulci that are located in association cortices and are often associated with human-specific aspects of cognition. Here, we manually defined 4,362 PMC sulci in 432 hemispheres in 216 human participants (50.5% female) and found that these smaller putative tertiary sulci showed more age- and AD-related thinning than larger, more consistent sulci, with the strongest effects for two newly uncovered sulci. A model-based approach relating sulcal morphology to cognition identified that a subset of these sulci was most associated with memory and executive function scores in older adults. These findings lend support to the retrogenesis hypothesis linking brain development and aging, and provide new neuroanatomical targets for future studies of aging and AD. Significance Statement Large-scale changes in cortical structure in aging suggest sulci are particularly vulnerable to atrophy. However, tertiary sulci, the smallest and most individually variable cortical folds associated with cognitive development, have not been studied in aging. Here, we investigate tertiary sulci for the first time in aging and Alzheimer's disease (AD). We find that these smaller and shallower sulci show more age- and AD-related thinning than larger sulci in posteromedial cortex (PMC), and that the atrophy of a subset of PMC sulci is most associated with cognition in older adults. These findings support classical theories linking developmental and aging trajectories at a novel anatomical resolution and provide insight into relationships between individual differences in structural brain changes and cognitive decline.

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)0.001
metaresearch head score (Gemma)0.003
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 score0.004
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0020.001
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.001
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 head0.057
GPT teacher head0.316
Teacher spread0.258 · 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

Citations28
Published2024
Admission routes1
Has abstractyes

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