Brain-Derived Neurotrophic Factor Genotype and Cognitive Functioning in Individuals with Cardiovascular Disease

In addition to an elevated mortality risk, cardiovascular disease (CVD) is a known contributor to cognitive decline and the onset of neurological conditions like Alzheimer’s disease. The mechanisms by which CVD contributes to cognitive problems are still being determined; recent work has begun to implicate genetic markers for risk of neurocognitive decline. One possible genetic mechanism is brain-derived neurotrophic factor (BDNF), a nerve growth factor whose serum levels are controlled by the polymorphism Val66Met. Serum BDNF provides support for various types of neurons. It is believed that MET allele produces reduced serum levels of BDNF, placing the individual at risk for poor neurocognitive outcome. Previous studies in samples of healthy middle-age and older adults have shown observed deficits in attention, memory, general intelligence, and visuospatial abilities in carriers of the MET allele. The present study examined the relationship between BDNF genotype and cognitive functioning in individuals with CVD. Participants (N=137) were recruited from outpatient cardiology clinics. All underwent a blood draw to assess the BDNF genotype as well as a comprehensive neuropsychological test battery. The sample was separated into two groups: carriers of the MET allele (N=38) and VAL/VAL homozygotes (N=99). Analyses compared groups on test performance in key cognitive domains. Analyses were then repeated and conducted separately for males and females, as previous studies had found sex differences. Analyses found group differences on tests of nonverbal memory, processing speed, and visual-motor integration. However, these results were not in the expected direction, as individuals with a MET allele actually performed better on these tasks. In females, BDNF genotype groups differed on memory tasks, with the MET carriers again performing better. No between-group differences emerged in males. These findings suggest the association between BDNF genotype and cognitive function differs in older adults with CVD relative to younger and healthier groups. One possible explanation for these differential findings is that there is an interaction between BDNF genotype and cardiac functioning, as recent research implicates BDNF in the cardiac response to stress. Another explanation is that CVD influences the control of BDNF genotype on circulating BDNF levels. Future studies should examine both genetic and serum levels of BDNF when looking at cognitive functioning medically ill populations to provide greater insight into the inconsistent findings.