The Influence of the BDNF Val66Met Polymorphism on the Association of Regular Physical Activity With Cognition Among Individuals With Diabetes

Biol Res Nurs. 2021 Jul;23(3):318-330. doi: 10.1177/1099800420966648. Epub 2020 Oct 16.


Introduction: Diabetes is associated with cognitive dysfunction that comes with substantial lifetime consequences, such as interference with diabetes self-management and reduced quality of life. Although regular physical activity has been consistently shown to enhance cognitive function among healthy subjects, significant interpersonal differences in exercise-induced cognitive outcomes have been reported among brain-derived neurotrophic factor (BDNF) Val/Val vs. Met carriers. However, the evidence on how the BDNF Val66Met variant influences the relationship between regular physical activity and cognition among individuals with diabetes is currently lacking.

Methods: A total of 3,040 individuals with diabetes were included in this analysis using data from the Health and Retirement Study. Associations among moderate and vigorous physical activities (MVPA) and measures of cognitive function were evaluated using multivariable linear regression models within each stratum of the Val66Met genotypes.

Results: MVPA was more strongly associated with total cognitive score, mental status, and words recall among Met/Met carriers, compared to Val/Val and Val/Met carriers.

Conclusions: This study provided preliminary findings on how BDNF variants may modulate the exercise-induced cognitive benefits among mid-aged and older adults with diabetes. Given the limitations of the current study, it is necessary for randomized controlled trials to stratify by BDNF genotypes to more conclusively determine whether Met carriers benefit more from increased physical activity. In addition, future research is needed to examine how the interplay of BDNF Val66Met variants, DNA methylation, and physical activity may have an impact on cognitive function among adults with diabetes.

Keywords: brain-derived neurotrophic factor; cognition; diabetes mellitus; exercise; gene-environment interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain-Derived Neurotrophic Factor* / genetics
  • Cognition*
  • Diabetes Mellitus* / genetics
  • Diabetes Mellitus* / psychology
  • Exercise*
  • Genotype
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Quality of Life


  • Brain-Derived Neurotrophic Factor