[P1–082]: COMBINED MEMANTINE AND VITAMIN D TREATMENT PROVIDES THE SAME COGNITIVE BENEFIT AS MEMANTINE ALONE IN A CHRONICALLY VITAMIN D DEFICIENT DOUBLE‐TRANSGENIC MOUSE MODEL OF ALZHEIMER'S DISEASE
Bibliographic record
Abstract
Amyloid-beta peptides, a hallmark of Alzheimer's disease (AD) pathology, have been shown to increase extracellular glutamate concentrations and L-type voltage-gated calcium channel (LVGCC) activity and expression, leading to calcium toxicity in neurons. Memantine, a moderate-affinity uncompetitive NMDA receptor antagonist, and Vitamin D (VitD), a neurosteroid hormone that can lower LVGCC expression, may have complementary protective effects against calcium toxicity in AD. Since low vitD (<30 ng/mL) is highly prevalent (70–90%) in AD patients, this study aimed to investigate the effect of memantine and VitD supplementation on cognition in a VitD deficient mouse model of Alzheimer's disease. 40 VitD deficient APPSwe/PS1-dE9 mice were studied using an interventional design with three parallel arms. All mice were fed a VitD deficient diet (<1 IU/kg) from 6 to 9 months of age to establish VitD deficiency. At 9 months of age, three different interventions were applied. Mice were given memantine only (25 mg/kg/day, n=13), memantine with VitD supplementation (25 mg/kg/day, 10,000 IU/kg VitD3, n=14), or no treatment (n=13). At 12 months of age, physical ability, anxiety, and memory were assessed using grip-strength and wire-hang, elevated plus maze, and Morris Water Maze (MWM), respectively. Serum 25(OH)D levels and body weight were also measured. At 9 months of age, mean serum 25(OH)D was 4.52 ng/mL (s=1.19, 2 outliers removed), confirming VitD deficiency. At 12 months of age, lower serum 25(OH)D was observed in the group treated with memantine only (p<0.05) and in the group receiving no treatment (p<0.0001), compared to the group receiving memantine and VitD supplementation. After adjusting for differences in physical ability, anxiety, and weight, mice receiving memantine only or memantine with VitD supplementation performed better than mice receiving no treatment (p<0.05, d=0.98; p<0.05, d=1.07), as measured by proximity to the target region during the MWM probe trial. No differences were found between mice receiving memantine only or memantine with VitD supplementation.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".