Lipid peroxidation in patients with vascular mild cognitive impairment from a memory and antioxidants in vascular impairment trial (MOVE‐IT)
Bibliographic record
Abstract
Abstract Background Oxidative stress (OS) has been a target of interest for vascular dementia, given its implications in pathogenesis. OS may be important in prodromal stage, such as vascular mild cognitive impairment (vMCI), and examining OS markers in vMCI may help better understand biological processes in the onset of cognitive impairment. Our study compared OS levels in vMCI vs controls, and explored whether OS markers predicted the response to antioxidant treatments in vMCI. Method Cardiac rehabilitation patients with cardiovascular risk factors (CVRFs) were recruited as vMCI (1SD below norms in executive function (EF), memory, processing speed or working memory) or cognitively‐healthy controls. vMCI patients were classified as probable vMCI if they had neuroimaging evidence of vascular pathology. vMCI patients were randomized to 2400mg N‐acetylcysteine (NAC) or placebo in a 24‐week, double‐blind trial. Serum 8‐isoprostane (8ISO), 4‐hydroxynonenal (4HNE) and lipid hydroperoxides (LPH) collection and cognitive assessments were done at three time points. ANCOVA models adjusting for age, sex and CVRFs compared OS markers between groups at baseline. Linear mixed‐effects models were used for longitudinal analyses. Result LPH levels were significantly lower in vMCI (n = 60) compared to controls (n = 16) (0.86±0.45 vs 1.18±0.31, F(1,62) = 7.0, p = 0.011). 4HNE were significantly higher in vMCI compared to controls (1.03±0.06 vs 0.99±0.04, F(1,70) = 6.6, p = 0.012). vMCI patients had significantly higher 4HNE/LPH (0.17±0.44 vs –0.18±0.29, F(1,62) = 9.3, p = 0.003) and (8ISO+4HNE)/LPH ratio (0.41±0.45 vs 0.13±0.38, F(1,62) = 5.9, p = 0.018) compared to controls. In probable vMCI group (n = 25), there was significant decreases in 4HNE/LPH (β = ‐0.68, SE = 0.27, p = 0.02) and (8ISO+4HNE)/LPH ratio (β = ‐0.65, SE = 0.28, p = 0.028) after NAC treatment. A significant time by baseline 8ISO effect on EF in the NAC group was observed (β = 0.78, SE = 0.26, p<0.01) after adjusting for age, sex and education. Conclusion This study showed that the ratios of late‐ to early‐phase lipid peroxidation markers were significantly elevated in vMCI groups compared to controls. This aligns with existing literature that altered lipid peroxidation may be implicated in vMCI. Antioxidant treatments decreased OS in probable vMCI groups, and higher baseline 8ISO was associated with greater improvement in EF in the NAC group, suggesting that probable vMCI patients with high OS may be appropriately targeted for antioxidant treatments.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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".