Cognition after stroke: findings on the BDNF Val66Met variant remain conflicting

Seven observational studies, with no pooled estimate

The review examines the association between the BDNF Val66Met variant, also identified as rs6265, and cognitive outcomes in adults who have had a stroke. BDNF is involved in neuroplasticity. This biological role explains researchers’ interest, but does not demonstrate that this variant determines cognitive recovery.

The authors included seven studies totaling 2,494 participants. They conducted a narrative synthesis rather than a meta-analysis because of substantial differences between the populations, genetic classifications and cognitive tests used. The source dossier does not provide the follow-up duration for each study.

A signal for memory, but no consistent direction

Five studies assessed overall cognition. Four reported statistically significant associations or differences by genotype: three observed less favorable outcomes in carriers of the Met allele, while one found the opposite.

In the largest cohort, Met carriers had lower scores on the telephone-administered Montreal Cognitive Assessment at 12 months, after adjustment for covariates. The abstract specifies neither the score difference nor its uncertainty, making it impossible to assess its clinical importance here.

Memory was the domain showing the most consistent signal, with poorer performance in Met carriers. Findings for language were conflicting, and data on attention and executive functions remained limited.

What this review cannot determine

These observational studies show associations, not a causal relationship. The divergent findings across populations also prevent a single conclusion from being applied to all adults after stroke.

This review therefore does not demonstrate the usefulness of genetic testing to guide rehabilitation or provide an individual prognosis. The authors call for larger multicenter prospective studies with standardized cognitive assessments.

What we can take away

The BDNF Val66Met variant offers a potential avenue for understanding cognitive differences after stroke, especially in memory. It is not a validated tool for individual prediction.