Peripheral blood leukotriene B4 and E4 as biomarkers in Alzheimer’s disease
Bibliographic record
Abstract
Abstract Background We showed recently that use of leukotriene receptor antagonists, typically used in asthma therapy, was associated with preserved executive function among people with Alzheimer’s disease (AD) dementia. The aim of this study was to determine if leukotriene B4 (LTB4) and E4 (LTE4) would be associated with longitudinal changes in cognitive performance and cerebrovascular disease markers in people with AD. Method Participants with clinical AD or mild cognitive impairment were identified from the Ontario Neurodegenerative Disease Research Initiative. LTB4 and LTE4 were extracted from fasting serum and quantified using ultra‐high performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS). Concentrations below the limit of detection were imputed using quantile regression imputation of left‐censored data. Cognition was assessed using composite scores for executive function (Trails Making Test B, Symbol Digit Modalities Test, Stroop switching task, and verbal fluency) and memory (Rey Auditory Verbal Learning Test and Brief Visuospatial Memory Test). White matter hyperintensities (WMH), lacunes, and perivascular spaces (PVS) were quantified using T2‐weighted structural magnetic resonance imaging (MRI). Longitudinal associations between baseline LTB4 or LTE4 and cognition and imaging markers at baseline and 1‐year‐follow‐up were assessed using mixed‐effects linear regression models, controlling for baseline demographic factors, medication use, and vascular comorbidities. Findings were corrected for multiple comparisons using a 5% false discovery rate. Result Among 158 participants (mean age = 69.22 years, 51% female, mean education = 14.61 years), higher baseline concentrations of LTB4 were not associated with performance in executive function or memory over time nor with changes in WMH, lacunes, or PVS over time. Higher baseline concentrations of LTE4 were associated with better performance in memory over time (β = 0.153 [95% CI = 0.026, 0.287]; however, this finding did not survive correction for multiple comparisons (adjusted p = 0.260; Table 1). Conclusion In a group of patients with AD, higher LTB4 and LTE4 in serum were not associated with changes in cognitive performance nor markers of cerebrovascular disease. These findings suggest very little potential for serum leukotrienes as biomarkers for cognitive decline of cerebrovascular disease progression in 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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| 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".