Urinary Brain-Derived Neurotrophic Factor as a Biomarker of Executive Functioning

Abstract

Background/Aims: Neurotrophins such as brain-derived neurotrophic factor (BDNF) are vital for neuronal survival and adaptive plasticity. With high BDNF gene expression in the prefrontal cortex, BDNF is a potential regulatory factor for building and maintaining cognitive reserves. Recent studies suggest that individual differences in executive functioning, a broad cognitive domain reliant upon frontal lobe structure and function, are governed in part by variance in BDNF polymorphisms. However, as neurogenetic data are not necessarily indicative of in vivo neurochemistry, this study examines the relationship between executive functioning and the neurotransmitter by measuring peripheral BDNF levels. Methods: Fifty-two healthy young adults completed a battery of standardized executive function tests. BDNF levels, adjusted for creatinine, were quantified with enzyme-linked immunosorbent assay of urine samples taken at the time of testing. Results: BDNF concentration was positively associated with cognitive flexibility but had no relationship with working memory, abstract reasoning/planning, self-monitoring/response inhibition, or fluency. Conclusions: These results individuate cognitive flexibility as the specific facet of executive functioning associated with in vivo BDNF levels. This study also validates urinary BDNF as a peripheral biomarker of cognition in healthy adults.

Brain-derived neurotrophic factor serum levels correlate with cognitive performance in Parkinson’s disease patients with mild cognitive impairment

“…Our results are congruent with previous data reported in both animal and human studies that documented an association between BDNF-related activity and cognitive functioning (Koven and Collins, 2014 ; Robbins and Cools, 2014 ), particularly with data suggesting a specific association with abilities in the executive system domain (Gajewski et al, 2011 ; Alfimova et al, 2012 ; Lu et al, 2012 ; Tükel et al, 2012 ; Koven and Collins, 2014 ). In fact, molecular studies reported that the BDNF gene polymorphism (Val66Met) may affect executive functions in healthy subjects (Alfimova et al, 2012 ) and in patients with psychiatric disturbances (Lu et al, 2012 ; Tükel et al, 2012 ).…”

“…In fact, molecular studies reported that the BDNF gene polymorphism (Val66Met) may affect executive functions in healthy subjects (Alfimova et al, 2012 ) and in patients with psychiatric disturbances (Lu et al, 2012 ; Tükel et al, 2012 ). Very interestingly, Koven and Collins ( 2014 ), who adopted a design similar to ours, recently documented a significant relationship in healthy subjects between (urinary) BDNF concentration and performance on executive tests. These authors examined a sample of more than 50 healthy young subjects who were administered a neuropsychological test battery investigating different subcomponents of the executive system.…”

“…Following Koven and Collins ( 2014 ), to investigate the possible correlation between BDNF levels and specific components of the executive domain (abstract reasoning/planning, self-monitoring/response inhibition, cognitive flexibility, fluency and working memory), individual z -scores were computed for each executive component by averaging the subjects’ z -scores on the relative tests. Thus, an individual score was obtained for abstract reasoning/planning (total accuracy score on the Zoo Map Test; number of categories achieved on the MCST; accuracy score on the Progressive Matrices), Self-monitoring/Response inhibition (Errors made on the Zoo Map Test; errors made and response times on interference condition of the Stroop test), Cognitive Flexibility (perseverative errors committed on the MCST; accuracy score on Alternate Phonemic and Semantic fluency; Trail Making Test Part B-Part A score), Fluency (Phonemic and Semantic fluency), and Working memory (Digit and Corsi span backward).…”

“…To test this hypothesis, we performed a pilot study with a groups of individuals with PD and MCI, in which we assessed BDNF serum levels and correlated them with scores obtained on tests measuring episodic memory, language, attention, executive and visual-spatial functions. Since in humans BDNF has been reported to correlate with specific components of the executive domain that are precociously weakened in PD (Koven and Collins, 2014 ), we expected to find a significant association between BDNF serum levels and PD patients’ performance on executive tests.…”

“…As for human data, in both healthy individuals (Alfimova et al, 2012 ) and in persons with psychiatric disturbances (Lu et al, 2012 ; Tükel et al, 2012 ), BDNF gene polymorphism (Val66Met) was found to be associated with executive dysfunctions. In a sample of more than 50 healthy young subjects, Koven and Collins ( 2014 ) recently documented a significant correlation between (urinary) BDNF concentration and cognitive performance on tests tapping cognitive flexibility (i.e., Trail Making Test, Design Fluency and Verbal Category Switching). Nonetheless the role of BDNF gene polymorphism in Parkinson’s disease (PD) is not well defined and the results are sometimes contradictory.…”