Significant Destructive Interaction of BDNF Val>Met Polymorphism with Stroke Severity and Family History of Dementia for Cognitive Impairments.

Purpose: The patients with more severe stroke, have more chance to develop higher levels of cognitive impairments; and family history of dementia as a genetic background, can give rise to an increased risk of the severity of cognitive deterioration. In this study, we sought to investigate whether the risk alleles of Val66Met of brain-derived neurotrophic factor (BDNF) polymorphism, has a destructive interaction with the stroke severity (SS) and family history of dementia (FHD) for cognitive impairments?

Method: In a case-control study, the carriers of at least one Val allele (n=56) were compared to the carriers of Met/Met homozygotes (n=156) in terms of FHD and SS (through National Institutes of Health Stroke Scale) on the north of Iran. To determine the cognitive functions, the third version of Addenbrooke's Cognitive Examination (ACE-III) was used.

Result: The mean age of patients was 64.52±11.71, and in average 202 day had passed from their stroke. The interactive effects of genotypes Val66Met BDNF with SS[F=8.95, ή2=0.04, P=0.003] and FHD[F=4.59, ή2=0.02, P=0.03] were significant for total score of ACE-III. It means that the Met/ Met homozygosity, modulated the effect of risk factors of SS and FHD on the cognitive function. Such homozygosity protects the attentional function and language abilities against the SS and FHD(P≤0.05).

Conclusion: It can be speculated that presence of Val/Met heterozygosity has a destructive interaction with the SS and FHD for decreasing the cognitive function, particularly in attention and language domains. Our findings suggested that the inhibition of signaling and trafficking of Val/Met heterozygosity is possibly a practical strategy in reducing the cognitive impairments following the stroke.