Clinical and Striatal Dopamine Transporter Predictors of Mild Behavioral Impairment in Drug-Naive Parkinson Disease

Abstract

Purpose: Neuropsychiatric symptoms are important and frequent nonmotor features in Parkinson disease (PD). We explored mild behavioral impairment (MBI) in drug-naive patients with PD and its clinical and dopamine transporter (DAT) correlates.

Methods: We recruited 275 drug-naive patients with PD who had undergone Unified Parkinson's Disease Rating Scale, a neuropsychological battery, Neuropsychiatric Inventory, and N-(3-[F]fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) PET within 6 months. Patients with PD were divided into groups without MBI (PD-MBI-, n = 186) and with MBI (PD-MBI+, n = 89) according to the Neuropsychiatric Inventory. We performed comparative analysis of DAT availability, cognitive function, and motor deficits between the groups.

Results: Mild behavioral impairment was found in 32.4% of PD patients at the time of diagnosis, and affective dysregulation and decreased motivation were the 2 most common neuropsychiatric domains. Dopamine transporter availability in the anterior caudate (odds ratio, 0.60; P = 0.016) and anterior putamen (odds ratio, 0.58; P = 0.008) was associated with the development of MBI in PD. PD-MBI+ group had a lower z-score in memory-related tests and Stroop color reading test than PD-MBI- group. PD-MBI+ group had a higher Unified Parkinson's Disease Rating Scale motor score after controlling for DAT availability in the posterior putamen than PD-MBI- group (P = 0.007).

Conclusions: This study suggests that early behavioral impairment is associated with more pathological involvement in the anterior striatum, memory and frontal dysfunction, and motor deficits, which could be regarded as a different phenotype in PD.