Effect of allopurinol and other xanthine oxidase inhibitors on oxidative stress in Alzheimer’s disease: A systematic review and meta-analysis (2015–2025)
Bibliographic record
Abstract
Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and neuropathology. Accumulating evidence implicates oxidative stress in AD pathogenesis. Xanthine oxidase (XO) is a major enzymatic source of reactive oxygen species in purine metabolism. XO inhibitors (e.g., allopurinol, febuxostat, topiroxostat) reduce XO-derived radicals and may thus ameliorate oxidative damage in the brain. We aimed to systematically review preclinical and clinical studies from 2015–2025 examining whether XO inhibition reduces oxidative stress markers, improves cognitive outcomes, or lowers dementia risk in AD. Methods: We searched PubMed, Scopus, Web of Science, and Google Scholar (2015–2025) using keywords combining “Alzheimer OR dementia” with “xanthine oxidase OR allopurinol OR febuxostat OR topiroxostat” and “oxidative stress OR cognitive OR dementia incidence”. Inclusion criteria were English-language studies on AD or related dementia assessing XO inhibitor effects on oxidative stress biomarkers, cognitive performance, or dementia incidence. We included both preclinical (animal in vitro experiments and in vivo models) and clinical (observational or interventional) studies. Screening, data extraction, and bias assessments (SYRCLE for animal studies, Newcastle–Ottawa Scale for observational studies, Cochrane tools for trials) were performed by two independent reviewers (blinded as XX and YY). A PRISMA flow diagram was constructed to map study selection.
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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 | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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 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".