The Brain-Derived Neurotrophic Factor Functional Polymorphism and Hand Grip Strength Impact the Association between Brain-Derived Neurotrophic Factor Levels and Cognition in Older Adults in the United States.

Introduction: Aging is associated with subtle cognitive decline in attention, memory, executive function, processing speed, and reasoning. Although lower brain-derived neurotrophic factor (BDNF) has been linked to cognitive decline among older adults, it is not known if the association differs among individuals with various BDNF Val66Met (rs6265) genotypes. In addition, it is not clear whether these associations vary by hand grip strength or physical activity (PA).

Methods: A total of 2904 older adults were included in this study using data from the Health and Retirement Study. Associations between serum BDNF and measures of cognitive function were evaluated using multivariable linear regression models stratified by Met allele status. PA and hand grip strength were added to the model to evaluate whether including these variables altered associations between serum BDNF and cognition.

Results: Mean age was 71.4 years old, and mean body mass index was 28.3 kg/m². Serum BDNF levels were positively associated with higher total cognitive score (beta = 0.34, p = .07), mental status (beta = 0.16, p = .07), and word recall (beta = 0.22, p =.04) among Met carriers, while serum BDNF levels were negatively associated with mental status (beta = -0.09, p = .07) among non-Met carriers. Furthermore, associations changed when hand grip strength was added to the model but not when PA was added to the model.

Conclusions: The BDNF Val66Met variant may moderate the association between serum BDNF levels and cognitive function in older adults. Furthermore, such associations differ according to hand grip strength but not PA.