engleski

Preliminary study of the cognitive function and val66met polymorphism in the brain-derived neurotrophic factor gene in patients with dementia and mild cognitive impairment

Introduction: Brain derived neurotrophic factor (BDNF) plays an important role in neuronal survival, differentiation, and synaptic plasticity in the brain. Reduced BDNF levels are found in dementia and cognitive decline. BDNF is controlled by a functional polymorphism, which consists of a substitution of valine (Val) into methionine (Met). This BDNF val66met polymorphism has been implicated in lower depolarization-induced production of BDNF, lower n-acetyl asparatate content, and reduced hippocampal activation during memory processing. The Met allele has been associated with reduced delayed episodic memory or working memory performance, but also with enhanced verbal reasoning ability. Aim: The hypothesis was that BDNF genetic variants may be associated with cognitive function in patients with dementia and mild cognitive impairment (MCI). Methods: A Val66Met polymorphism of the BDNF-gene was studied in 40 patients with dementia and in 13 patients with mild cognitive impairment (MCI). The association of BDNF val66met with neurological and cognitive status in patients with dementia and MCI was examined using the MMSE, NPI, ADAS-COG, CDT, Word pairs learning and recall/ Picture pairs learning and recall test and Visual attention tests. DNA from blood was extracted using the DNeasy Blood and Tissue Kit (Qiagen). In DNA samples BDNF polymorphism was genotyped by a TaqMan (Applied Biosystems) analysis. Results were evaluated using one-way ANOVA followed by the Tukey’ s test. The Hardy-Weinberg analysis was used to test the equilibrium of the population. The differences in the genotype and allele frequencies were evaluated using a  2 test. Results: The genotype and allele frequencies for Val66Met polymorphism did not differ significantly between control subjects, and patients with dementia or MCI. Patients with dementia and MCI differed significantly (p=0.035-0.001, ANOVA) in age, duration of disease, MMSE, modified MMSE, ADAS, NPI, NPI apathy and CDT scores. When subdivided according to the BDNF variants, patients with dementia differed significantly (F=8.422 ; p=0.012) only in the NPI disinhibition scores, while patients with MCI had significantly different (F=4.997 ; p=0.047) scores on Word pairs learning and recall/ Picture pairs learning and recall test (time of un-correct answers). The observed genotype distribution in patients with dementia ( 2=0.97) and MCI ( 2=0.69) did not differ significantly (P 0.05) from the expected Hardy– Weinberg equilibrium. Conclusion: The results from this preliminary study, showing that carriers of Val/Val genotype had better NPI disinhibition scores in dementia and shorter time of incorrect answers in MCI, are in line with the lower BDNF activity in Met/Met carriers. Although homozygosity for the Val allele was reported to confer an increased risk for dementia, no significant differences were found in the frequency of BDNF variants among patients or between patients and control subjects.

cognitive function; val66met polymorphism in the brain-derived neurotrophic factor gene; dementia; mild cognitive impairment

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