Oxidative stress mediates the effect of apathy on executive function in those at risk of vascular cognitive impairment
Bibliographic record
Abstract
Abstract Background People with coronary artery disease (CAD) are at a high risk of developing mild vascular cognitive impairment and those with cognitive decline have been shown to have higher ratios of late to early lipid peroxidation markers indicating oxidative stress. Neuropsychiatric symptoms can precede biomarker abnormalities e.g., depressive symptoms. Apathy has previously been linked to cognitive impairment, particularly executive dysfunction, but the physiological pathways underlying this relationship have not been investigated. This study investigated whether oxidative stress mediates a relationship between apathy and executive function in CAD. Method Participants with CAD were identified from a Cardiac Rehabilitation Program at the time of intake. The Apathy Evaluation Scale (AES) was used to measure apathy and executive function (EF) was measured via FAS test for phonemic fluency, animal naming test for semantic fluency and trails making test B. Markers of late (8‐isoprostane, 8‐ISO) and early (lipid hydroperoxides, LPH) lipid peroxidation/oxidative stress were measured in the serum. Mediation effects were tested using the PROCESS macro (version 3.4) for SPSS. A bias corrected inferential bootstrapping method with 10,000 permutations was used to obtain a 95% confidence interval (CI) for the indirect effect. Result Among patients with CAD (n=214, 20% women, mean±SD age= 63.2±7.5 years, years of education [YOE]= 15.8±3.4, AES score= 28.2±8.7, composite z score for EF= ‐0.18±0.71), the ratio of 8‐ISO to LPH mediated the relationship between apathy and EF in a model controlling for age, sex and YOE. The standardized regression coefficients between apathy and ratio of 8‐ISO to LPH (0.4961, p=0.02) and that between the ratio of 8‐ISO to LPH and EF (‐0.0053, p=0.005) were both statistically significant. Bootstrapping produced a statistically significant unstandardized indirect effect (‐0.0027 95% CI: ‐0.0087, ‐0.0007). Conclusion The results suggest that oxidative stress, specifically late markers of lipid peroxidation, plays a role in facilitating the relationship between apathy and executive dysfunction in those with CAD. As apathy is a strong predictor of conversion from cognitively normal to mild cognitive impairment, understanding mediators may suggest treatment targets.
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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 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".