AbstractBackgroundWhile the association between alpha‐synuclein gene promoter (Rep1) variability and risk of PD is well established, its association with cognition is unclear.ObjectivesTo investigate the association between Rep1 and motor and cognitive outcomes in PD.MethodsRep1 allele lengths were determined in 172 PD patients who were grouped into “long” and “short” carriers according to previous methods. Multivariable regression analysis was performed to investigate the effect of Rep1 length on cognitive and motor scores.ResultsLong Rep1 allele carriers had significantly lower MMSE (P = 0.010) and higher UPDRS Part III (P = 0.026) and H & Y (P = 0.008) scores compared to short allele carriers (controlled for age, sex, and disease duration). Interaction analyses of Rep1 with apolipoprotein 4 revealed no significant effect on clinical outcomes.ConclusionsPD patients carrying long Rep1 alleles are more impaired on cognitive and motor function independent of apolipoprotein 4 genotype. © 2019 International Parkinson and Movement Disorder Society