Association of plasma P-tau181 with memory decline in non-demented adults
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.
Bibliographic record
Abstract
Abstract Alzheimer’s disease is the leading cause of dementia worldwide and is characterized by a long preclinical phase in which amyloid-β and tau accumulate in the absence of cognitive decline. In vivo biomarkers for Alzheimer’s disease are expensive, invasive and inaccessible, yet are critical for accurate disease diagnosis and patient management. Recent ultrasensitive methods to measure plasma phosphorylated tau 181 (p-tau181) display strong correlations with tau positron emission tomography, p-tau181 in CSF, and tau pathology at autopsy. The clinical utility of plasma-based p-tau181 biomarkers is unclear. In a longitudinal multicentre observational study, we assessed 1113 non-demented individuals (509 cognitively unimpaired elderly and 604 individuals with mild cognitive impairment) from the Alzheimer’s Disease Neuroimaging Initiative who underwent neuropsychological assessments and were evaluated for plasma p-tau181. The primary outcome was a memory composite z-score. Mixed-effect models assessed rates of memory decline in relation to baseline plasma p-tau181, and whether plasma p-tau181 significantly predicted memory decline beyond widely available clinical and genetic data (age, sex, years of education, cardiovascular and metabolic conditions, and APOEε4 status). Participants were followed for a median of 4.1 years. Baseline plasma p-tau181 was associated with lower baseline memory (β estimate: −0.49, standard error: 0.06, t-value: −7.97), as well as faster rates of memory decline (β estimate: −0.11, standard error: 0.01, t-value: −7.37). Moreover, the inclusion of plasma p-tau181 resulted in improved prediction of memory decline beyond clinical and genetic data (marginal R2 of 16.7–23%, χ2 = 100.81, P < 0.00001). Elevated baseline plasma p-tau181 was associated with higher rates of clinical progression to mild cognitive impairment (hazard ratio = 1.82, 95% confidence interval: 1.2–2.8) and from mild cognitive impairment to dementia (hazard ratio = 2.06, 95% confidence interval: 1.55–2.74). Our results suggest that in elderly individuals without dementia at baseline, plasma p-tau181 biomarkers were associated with greater memory decline and rates of clinical progression to dementia. Plasma p-tau181 improved prediction of memory decline above a model with currently available clinical and genetic data. While the clinical importance of this improvement in the prediction of memory decline is unknown, these results highlight the potential of plasma p-tau181 as a cost-effective and scalable Alzheimer’s disease biomarker.
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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 | 0.001 | 0.001 |
| 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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it