Discordant Alzheimer's neurodegenerative biomarkers and their clinical outcomes in older adults without dementia
Bibliographic record
Abstract
Abstract Background: In 2018 ATN framework, Alzheimer's neurodegenerative biomarkers comprised cerebrospinal fluid (CSF) total tau, 18 F-fluorodeoxyglucose-positron emission tomography, and brain atrophy. Although these biomarkers could be used interchangeably, some cases had discordant neurodegenerative biomarkers. Our aim was to assess the clinical outcomes of having discordant Alzheimer's neurodegenerative biomarkers. Methods: A total of 721 non-demented individuals from the Alzheimer's Disease Neuroimaging Initiative database were included and then further categorized into concordant negative, discordant, and concordant positive groups. Demographic distributions of the groups were compared. Longitudinal changes in clinical outcomes and risk of conversion were assessed using linear mixed-effects models and multivariate Cox proportional hazard models, respectively. Results: Discordant group was intermediate to concordant-negative and concordant-positive groups in terms of APOE ε4 positivity, CSF amyloid-beta and phosphorylated tau. Compared with concordant-negative group, discordant group deteriorated faster in cognitive scores (Mini-Mental State Examination, the Clinical Dementia Rating Scale-Sum of Boxes, and the Functional Activities Questionnaire) and demonstrated greater rates of atrophy in brain structures (hippocampus, entorhinal cortex and whole brain), and concordant-positive group performed worse over time than discordant group. Moreover, the risk of cognitive progression increased from concordant-negative to discordant to concordant-positive. The longitudinal results were validated in A+T+, cognitively normal and mild cognitive impairment individuals, and were also validated by applying different cut-offs for neurodegenerative biomarkers. Conclusions: Discordant neurodegenerative status denotes a stage of cognitive function which is intermediate between concordant-negative and concordant-positive. Identification of discordant cases would provide insights into intervention and new therapy approaches, particularly in A+T+ individuals. Moreover, this work may be a complement to the ATN scheme.
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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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.020 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.003 | 0.003 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.002 | 0.008 |
| Research integrity | 0.001 | 0.013 |
| Insufficient payload (model declined to judge) | 0.001 | 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.
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; both teacher heads agree on what is shown here.
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".