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Record W3048824820 · doi:10.3389/fdata.2020.00024

Statistical Disease Progression Modeling in Alzheimer Disease

2020· article· en· W3048824820 on OpenAlex
Lars Lau Rakêt

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueFrontiers in Big Data · 2020
Typearticle
Languageen
FieldMedicine
TopicDementia and Cognitive Impairment Research
Canadian institutionsnot available
FundersNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchNational Institutes of HealthGenentechIXICOH. Lundbeck A/SServierEisaiNorthern California Institute for Research and EducationBioClinicaF. Hoffmann-La RocheUniversity of Southern CaliforniaBiogenU.S. Department of DefenseMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeNovartis Pharmaceuticals CorporationPfizerEli Lilly and CompanyBristol-Myers SquibbNational Institute on AgingAlzheimer's AssociationFoundation for the National Institutes of Health
KeywordsCognitionDiseaseCognitive declineAlzheimer's diseaseCognitive testPsychologyEffects of sleep deprivation on cognitive performanceMedicineDementiaPsychiatryInternal medicine

Abstract

fetched live from OpenAlex

Background:The characterizing symptom of Alzheimer disease (AD) is cognitive deterioration. While much recent work has focused on defining AD as a biological construct, most patients are still diagnosed, staged, and treated based on their cognitive symptoms. But the cognitive capability of a patient at any time throughout this deterioration does not only reflect the disease state, but also the effect of the cognitive decline on the patient’s predisease cognitive capability. Patients with high predisease cognitive capabilities tend to score better on cognitive tests that are sensitive early in disease relative to patients with low predisease cognitive capabilities at a similar disease stage. Thus, a single assessment with a cognitive test is often not adequate for determining the stage of an AD patient. Repeated evaluation of patients’ cognition over time may improve the ability to stage AD patients and such longitudinal assessments in combinations with biomarker assessments can help elucidate the time dynamics of biomarkers. In turn, this can potentially lead to identification of markers that are predictive of disease stage and future cognitive decline, possibly before any cognitive deficit is measurable. Methods and Findings:This paper presents a class of statistical disease progression models and applies them to longitudinal cognitive scores. These nonlinear mixed-effects disease progression models explicitly model disease stage, baseline cognition, and the patients’ individual changes in cognitive ability as latent variables. Maximum-likelihood estimation in these models induces a data-driven criterion for separating disease progression and baseline cognition. Applied to data from the Alzheimer’s Disease Neuroimaging Initiative, the model estimated a timeline of cognitive decline that spans approximately 15 years from the earliest subjective cognitive deficits to severe AD dementia. Subsequent analyses demonstrated how direct modeling of latent factors that modify the observed data patterns provides a scaffold for understanding disease progression, biomarkers and treatment effects along the continuous time progression of disease. Conclusions:The presented framework enables direct interpretations of factors that modify cognitive decline. The results give new insights to the value of biomarkers for staging patients and suggest alternative explanations for previous findings related to accelerated cognitive decline among highly educated patients and patients on symptomatic treatments.

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.

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)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.725
Threshold uncertainty score0.414

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
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 head0.164
GPT teacher head0.382
Teacher spread0.218 · 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