Background and purpose: A possible association between Parkinson's disease (PD) and the polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different studies that nevertheless yielded-contrasting result. The purpose of this study was to analyze such possible association in a cohort of Italian PD patients. Methods: The BDNF polymorphisms were analyzed in 294 Italian patients with PD; results were compared to those obtained in 233 age- and sex-matched healthy controls (HC) enrolled from two tertiary centres in Italy. Polymorphisms were determined by Restriction Fragment Length Polymorphism (RFLP) analysis; correlations between BDNF G196A polymorphism, and cognitive function were established by sub analyzing the results upon dividing PD patients based on their Mini Mental State Examination (MMSE) score. Results: Univariate analysis showed a highly significant correlation between the BDNF(AA) genotype and a MMSE score 24 and HC (P