Association between BDNF Polymorphism (Val66Met) and Executive Function in Patients with Amnestic Mild Cognitive Impairment or Mild Alzheimer Disease

Abstract

Background: In the present study, we examined whether brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) influenced the changeable executive dysfunction of patients with two separate disease stages: amnestic mild cognitive impairment (A-MCI) or mild Alzheimer disease (AD), which are comparatively similar demented conditions. Methods: Among 200 outpatients with dementia and MCI, 146 outpatients with mild AD or A-MCI were recruited and divided into two genotypic groups, valine homozygosity (Val/Val) and methionine (Met) carriers, based on the representative BDNF functional polymorphism Val66Met. Next, we compared the Frontal Assessment Battery (FAB) total and subtest scores between the two genotypic groups according to each of two different disease stages: A-MCI (n = 42) and mild AD (n = 104). Results: Among patients with only a mild stage of AD, the FAB total and go/no-go scores were significantly lower (p < 0.05) among the subjects with the Val/Val genotype than among the Met carriers. However, no significant differences in any other demographic variables were observed between the genotypes according to each of different disease stages. A significant interaction between Val66Met and age was not observed for the FAB scores. Conclusion: These results suggested thatthe BDNF gene may significantly influence executive dysfunction, including inhibition tasks, among patients with mild-stage AD.

Association between Neurotrophin-3 Polymorphisms and Executive Function in Japanese Patients with Amnestic Mild Cognitive Impairment and Mild Alzheimer Disease

“…Our results may help to elucidate the functional roles of not only the NT-3 gene, but also other neurotrophin gene polymorphisms described in previous studies [17,18,23,24]. Furthermore, elucidating the detailed associations between NT-3 gene diversity and behaviors in patients with AD will be an important task in the future.…”

“…Moreover, NT-3 protects cortical neurons against A-β dependent neural cell death by limiting caspase-8, caspase-9 and caspase-3 cleavage [16]. While some previous studies have reported neurotrophin polymorphisms as a risk factor for AD in Japanese populations, our group reported that representative single-nucleotide polymorphisms (SNPs) of NGF and BDNF influenced executive function during limited demented stages, as assessed using the frontal assessment battery (FAB) [17][18][19][20][21].…”

“…The method used for the NT-3 SNP (rs6332, rs6489630) genotyping, a SNaPshot analysis (Applied Biosystem), has been described in previous reports [17,18,31]. If the genotype of the SNPs was unclear or ambiguous using the SNaPshot method, we rechecked and confirmed the genotype using PCR products and direct nucleotide sequencing with an ABI 3730 DNA analyzer (sequencing reactions were performed using BigDye Terminator v3.1 Cycle Sequencing Kits; Applied Biosystems).…”

BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention

“…In one study, Val/Val genotype occurred with higher frequency in those with AD compared to healthy controls 22 ; another study showed lower scores on the Frontal Assessment Battery in Val/Val homozygote patients with mild AD. 23 These discrepancies could possibly be explained by genetic differences between samples (i.e., lack of Hardy-Weinberg equilibrium), differences in disease stage at the time of analysis (probable AD vs preclinical AD), or cross-sectional design. In fact, in the present study, Met carriers performed better at baseline in the domains of verbal learning and memory (p 5 0.013) and speed and flexibility (p 5 0.002) (table 2) yet declined more steeply over time, emphasizing the importance of longitudinal design in studies of BDNF and cognition.…”

“…Carriage of 1 or 2 Met alleles is associated with lower BDNF production, 14 decreased hippocampal volume, 15 and cognitive decline. [16][17][18][19] However, null 20,21 and opposite findings 22,23 have been documented, making the relationship between BDNF and cognition in aging populations unclear.…”