Effect of vitamin D deprivation and subsequent treatment with memantine and vitamin D enrichment on gait in APP/PS1 Alzheimer’s mice
Bibliographic record
Abstract
Abstract Background Altered gait is a common complication of Alzheimer’s disease (AD) that leads to decreased mobility and quality of life. Additionally, many individuals with AD are vitamin D (vitD) deficient. Combined treatment with memantine and vitD has been shown to protect cortical axons from glutamate toxicity and beta‐amyloid in AD. Therefore, this treatment may mitigate changes in gait associated with AD. The purpose of this study was to assess for the first time in an AD mouse model whether gait is affected by vitD deprivation and whether subsequent treatment with memantine or memantine combined with high dose vitD reverses these effects. Method Male APP/PS1 mice were randomized into four groups. Controls (n=14) received a standard diet throughout. The other three groups started a vitD deficient diet at month 6. The VitD‐ group (n=14) stayed on this diet, while the remaining two groups began treatment at month 9 with either memantine alone (Mem&VitD‐) or both memantine and 10 IU/g vitD (Mem&VitD+). Serum 25(OH)D3 levels and spatiotemporal parameters of gait (stride length, swing time, swing speed, and front and hind stride widths measured by CatWalk) were assessed at months 6, 9, 12 and 15. Result Mice on vitD‐deficient diets had 7× lower levels of serum 25(OH)D3, and mice on the vitD‐enriched diet (Mem&VitD+) had over 2× higher levels of serum 25(OH)D3, relative to controls. VitD deprivation did not significantly affect stride length, swing time, swing speed, or front stride width, however, it led to a 12% increase in hind stride width by month 15 (Figure 1, VitD‐ vs. Control, p<0.001). Therefore, we examined hind stride width at month 15 in the memantine treatment groups and found that combination treatment with vitD prevented this increase (Figure 2, Mem&VitD+ vs. VitD‐, p<0.05), while memantine alone did not (Mem&VitD‐ vs. VitD‐, p=0.28). Conclusion VitD deprivation led to impaired postural control (hind stride width) in APP/PS1 mice by month 15. Memantine in combination with vitD enrichment, but not memantine alone, was able to prevent this impairment. Therefore, future work should investigate the potential for memantine combined with vitD supplementation to improve gait in people with AD.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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; 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".