QOL-53. METFORMIN RESULTS IN HIPPOCAMPAL REMODELING AND IMPROVED MEMORY ENCODING IN PAEDIATRIC BRAIN TUMOR SURVIVORS TREATED WITH CRANIAL RADIATION: A PILOT RANDOMIZED CONTROLLED CROSSOVER STUDY
Bibliographic record
Abstract
Although curative, cranial radiation results in hippocampal insult and memory impairment in children with brain tumours. Metformin stimulates hippocampal neurogenesis and improves memory performance in mice. We conducted a pilot double-blind randomized controlled cross-over trial to examine feasibility and test the effects of metformin versus placebo on hippocampal volume and declarative memory in pediatric brain tumor survivors treated with either focal or whole brain radiotherapy. Twenty-four participants (Age = 13.96 ± 3.51) (M=14, F=7) were randomly assigned to complete consecutive 12-week cycles of Metformin (A) and Placebo (B) in either an AB or BA sequence: 10-week washout occurred at crossover. Assessment at baseline and immediately following treatment for each condition included: (a) structural MRI to obtain overall/subfield hippocampal volume and (b) testing of memory encoding/retrieval. Linear mixed modelling was used to test the effects of treatment condition and time on difference from baseline scores: an interaction term was used to test for carryover. Adherence was high and participants tolerated metformin. No change in overall hippocampal volume was observed bilaterally - but increased volume in the right subiculum and fimbria was evident for metformin vs. placebo (p’s < .05). Notably, decreased right CA3 volume was evident for metformin carryover – suggesting a remodeling of hippocampal structure. Treatment with metformin resulted in improved memory encoding immediately and at carryover (p’s < .05). Metformin may be effective for normalizing hippocampal structure and memory encoding in paediatric brain tumor survivors and warrants consideration in larger trials.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".