title: BDNF polymorphism associates with decline in set shifting in Parkinson's disease.
abstract: Parkinson's disease (PD) is a neurodegenerative disorder caused by nigrostriatal dopaminergic degeneration. Brain-derived neurotrophic factor (BDNF) is a key protein in brain plasticity and is particularly important for survival of dopaminergic neurons. The Val66Met polymorphism of BDNF (rs6265) has been associated with functional differences (mainly cognitive) between healthy adults and also with differences in the clinical expression of several other neuropsychiatric illnesses including PD. However, these studies used different outcome measures, have not been replicated, and were cross sectional, making it difficult to establish the role of BDNF in the clinical variability of PD. Here, a large cohort of 384 PD patients were followed up for 2 years, and associations between BDNF genotype and various clinical characteristics were examined. The BDNF Met-allele carriers showed a significantly smaller decline in set shifting during follow-up compared with the homozygous BDNF Val-allele carriers. Contrary to previous assumptions, these results indicate that mental flexibility is one of the cognitive processes that may benefit from the BDNF Met allele in PD patients.
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Nicolien M
authors.initials: NM
authors.lastname: van der Kolk
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Arlene D
authors.initials: AD
authors.lastname: Speelman
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Marlies
authors.initials: M
authors.lastname: van Nimwegen
authors.affiliation: Department of Medical Psychology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Roy P C
authors.initials: RP
authors.lastname: Kessels
authors.affiliation: Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Joanna
authors.initials: J
authors.lastname: IntHout
authors.affiliation: Department of Human Genetics, Research Lab for Multifactorial Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Marina
authors.initials: M
authors.lastname: Hakobjan
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Marten
authors.initials: M
authors.lastname: Munneke
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Bastiaan R
authors.initials: BR
authors.lastname: Bloem
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: Bart.vandewarrenburg@radboudumc.nl.
authors.forename: Bart P
authors.initials: BP
authors.lastname: van de Warrenburg
mesh_terms: D000368:Aged; D000483:Alleles; D019208:Brain-Derived Neurotrophic Factor / Q000737:chemistry / Q000235:genetics*; D015331:Cohort Studies; D059290:Dopaminergic Neurons / Q000473:pathology; D056344:Executive Function; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009473:Neuronal Plasticity / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine
keywords: BDNF; Executive function; Parkinson's disease