title: The BDNF Val66Met polymorphism has a gender specific influence on planning ability in Parkinson's disease.
abstract: Parkinson's disease (PD) patients show a range of cognitive deficits,which may relate to abnormalities in dopaminergic transmission in fronto-striatal circuitry. In this study, we have investigated the impact of brainderived neurotrophic factor (BDNF) val66met polymorphisms on performance of the Tower of London (TOL) test of planning by PD patients. This polymorphism significantly influences BDNF secretion in the CNS, and BDNF is known to influence dopaminergic neurons and cognitive processes. Patients with PD totalling 291 who had undergone detailed motor and cognitive assessments as part of a population-based study of PD were genotyped for the BDNF val66met polymorphism. The impact of this polymorphism on cognitive ability was determined using multivariate analysis to adjust for possible confounding variables. Patients with low rates of BDNF secretion (met alleles) performed significantly better at the TOL task than those with high rates of secretion (val alleles). Furthermore, subgroup analyses revealed that the effect is most apparent in women and among patients with prior dopaminergic exposure. We speculate that BDNF may interact with dopaminergic transmission and dopamine receptor stimulation in the frontostriatal circuitry, with subsequent consequences on cognition in Parkinson's disease.
authors.affiliation: Cambridge Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK. tf210@medschl.cam.ac.uk
authors.forename: Thomas
authors.initials: T
authors.lastname: Foltynie
authors.forename: Simon G J
authors.initials: SG
authors.lastname: Lewis
authors.forename: Terry E
authors.initials: TE
authors.lastname: Goldberg
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Blackwell
authors.forename: Bhaskar S
authors.initials: BS
authors.lastname: Kolachana
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.forename: Roger A
authors.initials: RA
authors.lastname: Barker
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008606:Mental Processes / Q000502:physiology*; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010300:Parkinson Disease / Q000235:genetics / Q000503:physiopathology*; D011110:Polymorphism, Genetic; D012727:Sex Characteristics; D014633:Valine / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D014633:Valine