Vitamin D and the preclinical Alzheimer cognitive composite cognition (PACC) score: a two-sample mendelian randomization study
Bibliographic record
Abstract
ABSTRACT Objective Observational studies on cognition found that vitamin D supplementation is associated with improved cognition. Further, recent Mendelian randomization (MR) studies have shown that increased vitamin D levels, as measured by 25-hydroxyvitamin D [25(OH)D], may protect against Alzheimer’s disease. Thus, it is possible that 25OHD may protect against Alzheimer’s disease by improving cognition. Methods To evaluate this hypothesis, we began by performing an observational study by testing the association of 25OHD levels with 5 cognitive outcomes related to memory and executive function, adjusting for age, sex, BMI, smoking status and nutritional risk index in 26,787 older individuals (median age 62). Since such observational analyses can be biased by confounding, we next performed two-sample mendelian randomization (MR) analyses testing the effect of 25(OH)D on cognitive outcomes, since this method helps to protect against bias from confounding. Results Observational studies suggested a strong protective association between 25(OH)D and cognitive measures. However, in MR analyses, we found no estimated effect of 25(OH)D on these outcomes. Conclusion These findings suggest that associations between 25(OH)D levels and cognition are likely to be biased by confounding and that the relationship between 25(OH)D levels and Alzheimer’s disease is not due to the effect of 25(OH)D on cognition.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.032 | 0.065 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".