The Synergistic Impact of Astrocyte Reactivity and Vitamin D Deficiency on Post-Stroke Cognitive Impairment: A Systematic Review and Meta-Analysis
Bibliographic record
Abstract
Background: Post-stroke cognitive impairment (PSCI) is a common, debilitating outcome of ischemic stroke. Glial Fibrillary Acidic Protein (GFAP), marking astrocyte reactivity, and Vitamin D, a neuro-immunomodulatory steroid, are independently linked to PSCI. This study aimed to quantify the synergistic impact of elevated serum GFAP and concurrent Vitamin D deficiency on PSCI risk. Methods: Following PRISMA guidelines, a systematic search of PubMed, Scopus, and Web of Science was conducted for prospective cohort studies (2015-2025) assessing acute serum GFAP, 25-hydroxyvitamin D (25(OH)D), and subsequent cognitive outcomes in ischemic stroke patients. Quality was assessed using the Newcastle-Ottawa Scale. A meta-analysis of seven studies (n=3,850) was performed using a random-effects model to calculate pooled odds ratios (ORs) for PSCI across four biomarker-defined groups. A formal test for synergistic interaction was conducted by assessing the departure from additivity of effects on the log-odds scale. Results: Seven high-quality studies were included. Compared to the reference group (Normal GFAP/Sufficient Vitamin D), the pooled OR for PSCI was 2.18 (95% CI: 1.85-2.57) for high GFAP alone and 1.95 (95% CI: 1.65-2.30) for Vitamin D deficiency alone. For the dual-biomarker group (High GFAP/Deficient Vitamin D), the pooled OR was 4.75 (95% CI: 3.98-5.67). This observed risk was significantly greater than the 3.13 OR expected from a purely additive model (p for interaction < 0.001), confirming a significant synergistic effect. Sensitivity analysis showed the effect was most pronounced in patients with moderate-to-severe strokes (NIHSS > 5). Conclusion: Elevated serum GFAP and Vitamin D deficiency synergistically increase the risk of PSCI, particularly in patients with more severe strokes. The interplay between acute astroglial injury and compromised systemic neuroprotection appears to be a critical determinant of cognitive outcomes. While confounding by patient frailty requires further study, this dual-biomarker profile identifies a high-risk subgroup and highlights a key pathophysiological interaction.
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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 | 0.014 | 0.033 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.019 | 0.042 |
| Bibliometrics | 0.007 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| 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".