Catechol-O-methyltransferase (COMT) genetic variants are associated with cognitive decline in patients with Parkinson's disease.

OBJECTIVE:Catechol-O-methyltransferase (COMT), an enzyme that catalyzes the degradation of dopamine, is necessary for both motor and cognitive functions. Few studies have examined the association between COMT variants and cognition in patients with Parkinson's disease (PD). METHODS:We assessed a cohort of 409 PD patients without dementia who were regularly followed for two years. The Unified Parkinson's Disease Rating Scale (UPDRS) and Mini-Mental State Examination (MMSE) were administered at baseline and during the follow-up. The genetic variants and haplotypes of COMT, including rs6267, rs6269, rs4633, rs4818, and rs4680, were examined. RESULTS:No association was observed between COMT genotypes and baseline cognitive function. After a mean follow-up period of 647.3 days, MMSE scores deteriorated with age. Cognitive decline correlated with age (P < 0.05) but not with the motor severity defined using UPDRS part III scores (P = 0.21). Kaplan-Meier survival analyses showed that PD patients carrying the G allele of the rs6269 variant and COMT haplotypes constituting the G allele of rs6269 showed a significantly more rapid decline in the MMSE scores over the follow-up period (log-rank test, P < 0.01). Cox proportional regression analysis adjusted for covariates revealed that among patients with PD, those carrying the high-COMT activity haplotype (G_C_C_G for rs6269, rs4633, rs4818, and rs4680) showed a high risk of cognitive decline (hazard ratio = 3.24; P = 0.02). CONCLUSION:Our findings suggest that the high-COMT activity haplotype is associated with cognitive decline in patients with PD.