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Record W4410508205 · doi:10.3389/fneur.2025.1568086

AI-based staging, causal hypothesis and progression of subjects at risk of Alzheimer’s disease: a multicenter study

2025· article· en· W4410508205 on OpenAlexfundno aff
Simona Aresta, Raffaello Nemni, Moreno Zanardo, G. Sirabian, Dario Capelli, Marco Alì, Paolo Vitali, Enrico Giuseppe Bertoldo, Valentina Fiolo, Lilla Bonanno, Giuseppa Maresca, Petronilla Battista, Francesco Sardanelli, Francesca B. Pizzini, Isabella Castiglioni, Christian Salvatore

Bibliographic record

VenueFrontiers in Neurology · 2025
Typearticle
Languageen
FieldMedicine
TopicDementia and Cognitive Impairment Research
Canadian institutionsnot available
FundersCanadian Institutes of Health ResearchNational Institutes of HealthGenentechIXICOH. Lundbeck A/SServierEisaiNorthern California Institute for Research and EducationPfizerNovartis Pharmaceuticals CorporationUniversity of Southern CaliforniaBiogenEli Lilly and CompanyBristol-Myers SquibbBioClinicaU.S. Department of DefenseAlzheimer's Disease Neuroimaging InitiativeMeso Scale DiagnosticsAlzheimer's Association
KeywordsDementiaNeurocognitiveBiomarkerReceiver operating characteristicMedicineNeuropsychologyDiseaseInternal medicineOverdiagnosisNeuropsychological assessmentPsychologyOncologyCognitionPsychiatry

Abstract

fetched live from OpenAlex

Introduction In 2024, 11 European scientific societies/organizations and one patient advocacy association have defined a patient-centered biomarker-based diagnostic workflow for memory clinics evaluating neurocognitive disorders. Methods We tested the performance of an artificial intelligence (AI) tool applied to neuropsychological and magnetic resonance imaging (MRI) assessment for staging and causal hypothesis, which are the two recommended workflow steps guiding the next one recommending optimal biomarkers to be used for a biological diagnosis of neurocognitive disorders, according to intersocietal recommendations. Moreover, we assessed the AI performance in predicting the progression to Alzheimer’s disease (AD)-dementia. Results For the three-class classification of staging (n patients = 426), the inter-rater AI-humans agreement was substantial for both healthy subjects/subjective cognitive impairment/worried-well vs. all the remaining groups (rest) (Cohen’s κ = 0.81) and mild cognitive impairment/mild dementia vs. rest κ = 0.70) classification, almost perfect for moderate/severe dementia vs. rest κ =0.90) classification. For the three-class classification of causal hypotheses ( n = 112), the AI performance vs. biomarker-based diagnosis was: positive predictive value 91% [95% CI: 84–96%]; negative predictive value 100%, and accuracy 91% [84–96%]. For the binary classification of progression or not progression to AD-dementia at 24-month, with clinical conversion as a reference standard ( n = 341), the AI performance was: sensitivity 89% [84–94%], specificity 82% [77–87%]; accuracy 85% [81–89%]; and area under the receiver operating characteristic curve 83% [79–87%]. Discussion The AI tool showed high agreement with human assessment for staging, high accuracy with biomarkers for causal hypotheses of neurocognitive disorders and predicted progression to AD at 24-month with 89% sensitivity and 82% specificity.

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)0.019
metaresearch head score (Gemma)0.026
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 score0.019
Threshold uncertainty score0.102

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0190.026
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
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 head0.013
GPT teacher head0.315
Teacher spread0.302 · 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

Citations2
Published2025
Admission routes1
Has abstractyes

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