Associations of serum BDNF and Val66Met (rs6265) BDNF gene polymorphism with depressive symptoms and cognitive performance after ischemic stroke: a prospective cohort study.

AIM OF THE STUDY: To assess the association between serum brain-derived neurotrophic factor (BDNF) levels and depressive symptoms and cognitive performance after ischemic stroke, and to evaluate the impact of the BDNF Val66Met (rs6265) gene polymorphism on these relationships.

CLINICAL RATIONALE FOR THE STUDY: Post-stroke depression (PSD) and post-stroke cognitive impairment (PSCI) are frequent and often coexisting complications that markedly worsen quality of life and functional outcome in stroke survivors. BDNF is a key mediator of neuroplasticity, neuroprotection and mood regulation, and the Val66Met polymorphism has been implicated in vulnerability to depression and cognitive decline. However, data integrating BDNF, detailed neuropsychological profiles and genetic variability in stroke cohorts remain limited.

MATERIAL AND

METHODS

In this prospective cohort study, 110 patients with ischemic stroke and 33 age- and sex-matched controls were enrolled. Serum BDNF concentration was measured once at 7 days post-stroke (early subacute phase). Depressive symptoms were assessed with the Beck Depression Inventory-II (BDI-II) at 7 days and at 6 months after stroke. A comprehensive neuropsychological battery was applied at baseline and follow-up, including California Verbal Learning Test, Trail Making Test A and B, Stroop Color and Word Test, Digit Span, Verbal Fluency Tests and Montreal Cognitive Assessment. BDNF Val66Met genotype was determined in all stroke patients. Correlations and adjusted multivariable models were performed.

RESULTS

Baseline serum BDNF was inversely associated with baseline BDI-II score (adjusted Spearman rho = -0.256, p = 0.007), corresponding to an approximate 1.86-point reduction in BDI-II per 10,000 pg/mL increase in BDNF. No significant association was found with BDI-II at 6 months. Higher BDNF levels were consistently related to better cognitive performance, particularly faster processing speed and attention (shorter Stroop1 and Trail Making Test A times) at baseline and follow-up in adjusted analyses. BDNF concentrations and Val66Met genotype distributions did not differ between stroke and control groups. The Val66Met polymorphism did not modify BDNF-depression or BDNF-cognition associations, although Val/Val carriers showed higher baseline CVLT semantic clustering scores.

CONCLUSIONS

Higher serum BDNF levels are associated with less severe depressive symptoms and better cognitive performance after ischemic stroke, independent of major vascular risk factors. In this cohort, the BDNF Val66Met polymorphism had a limited impact, with only a modest association with a specific memory clustering measure. These findings support the clinical relevance of BDNF as a potential biomarker of mood and cognitive outcomes in stroke survivors and justify further studies incorporating longitudinal BDNF measurements and larger genetic datasets.