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All Journal Medicina E-Jurnal Medika Udayana Jurnal Kesehatan Andalas Damianus Journal of Medicine MNJ (Malang Neurology Journal) Callosum Neurology Journal : Jurnal Berkala Neurologi Bali ISM (Intisari Sains Medis) : Jurnal Kedokteran Bioscientia Medicina : Journal of Biomedicine and Translational Research Majalah Kedokteran Neurosains Bioscientia Medicina : Journal of Biomedicine and Translational Research Cermin Dunia Kedokteran Magna Neurologica Cermin Dunia Kedokteran
Anak Agung Ayu Putri Laksmidewi
Departemen Neurologi, Fakultas Kedokteran Universitas Udayana
Biochemistry, Genetics & Molecular Biology Health Professions Immunology & microbiology Medicine & Pharmacology Neuroscience Public Health

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The Synergistic Impact of Astrocyte Reactivity and Vitamin D Deficiency on Post-Stroke Cognitive Impairment: A Systematic Review and Meta-Analysis Patricia; Anak Agung Ayu Putri Laksmidewi; Kumara Tini
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 12 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i12.1449

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.
Co-Authors Adriana Marsha Yolanda Anna Marita Gelgel Arimbawa, I Komang Arshinta, Lasta Bagus Ngurah Mahasena Putera Awatara Dewa Putu Gede Purwa Samatra Dian Kusumastuti Anggraeni Putri Gde Putra Dhyatmika Gede Suputra I Gede Supriadhiana I Ketut Sumada I Made Oka Adnyana I Putu Eka Widyadharma I WAYAN WIDYANTARA Indah, Carolin Tiara Lestari Kelvin Yuwanda Ketut Widyastuti Kumara Tini Lasta Arshinta Mahadewi, Ni Putu Ayu Putri Mahendrakrisna, Daniel Ni Putu Witari Ni Wayan Nurlina Ekasari NKA, Sudiarini P. Gde Daniswara Raditya Rahman Patricia Putra, Ida Bagus Kusuma Putri Eka Pradnyaning Risky Ilona Saputra Suherlim, Richard Tertia, Clarissa Tirtha, Putu Bagus Bramanthana Trisnawati, Sri Yenni Valentina Tjandra Dewi Vania, Aurelia Yusari, I Gusti Agung Ayu Andra