Pre-stroke physical activity and Val66Met (rs6265) genotype of <i>BDNF</i> gene correlate with the post-stroke cognitive outcome: a prospective cohort study

Abstract Background Pre-stroke physical activity may protect against post-stroke cognitive impairment (PSCI) via neuroplastic mechanisms including BDNF signalling. However, evidence in stroke survivors and the modifying role of the BDNF Val66Met polymorphism remain limited. Methods In this prospective single-centre cohort, 97 patients with ischaemic stroke underwent detailed neuropsychological assessment during index hospitalisation and at 6-month follow-up. Pre-stroke activity was quantified as weekly MET-minutes (IPAQ scale). Serum BDNF and Val66Met genotype were measured. Associations between METs and cognitive outcomes (baseline, follow-up) were assessed with Spearman correlations and adjusted multivariable linear regression. Results Higher pre-stroke METs correlated with superior baseline performance across global cognition (MoCA), verbal learning/recall (CVLT indices), attention and executive measures. After adjustment, CVLT long-delay free recall (LDFR) and TMTA remained significant (β for CVLT LDFR ≈0.000097 per MET-min/week, p &lt; 0.05). At 6 months, METs were associated with multiple CVLT indices (SDCR, SDFR, LDFR) in adjusted models. All associations indicated positive correlation between physical activity and better cognitive outcome. Mean serum BDNF did not correlate with METs (mean 27,261 ± 7,967 pg/mL) and did not differ from controls. Val/Val (GG) carriers of Val66Met genotype of BDNF gene performed better cognitively than Met allele carriers, but the genotype did not correlate with serum BDNF level. Conclusions Greater self-reported pre-stroke physical activity was associated with better early and 6-month cognitive outcomes after ischaemic stroke, whereas peripheral BDNF levels were not correlated. Val66Met polymorphism of BDNF gene correlates with the cognitive outcome in stroke survivors but doesn’t enhance BDNF level, indicating effect on activity rather than quantity.