The impact of dopaminergic treatment over cognitive networks in Parkinson's disease: Stemming the tide?

Abstract

Dopamine-replacing therapies are an effective treatment for the motor aspects of Parkinson's disease. However, its precise effect over the cognitive resting-state networks is not clear; whether dopaminergic treatment normalizes their functional connectivity-as in other networks- and the links with cognitive decline are presently unknown. We recruited 35 nondemented PD patients and 16 age-matched controls. Clinical and neuropsychological assessments were performed at baseline, and conversion to dementia was assessed in a 10 year follow-up. Structural and functional brain imaging were acquired in both the ON and practical OFF conditions. We assessed functional connectivity in both medication states compared to healthy controls, connectivity differences within participants related to the ON/OFF condition, and baseline connectivity of PD participants that converted to dementia compared to those who did not convert. PD participants showed and increased frontoparietal connectivity compared to controls: a pattern of higher connectivity between salience (SN) and default-mode (DMN) networks both in the ON and OFF states. Within PD patients, this higher SN-DMN connectivity characterized the participants in the ON state, while within-DMN connectivity prevailed in the OFF state. Interestingly, participants who converted to dementia also showed higher SN-DMN connectivity in their baseline ON scans compared to nonconverters. To conclude, PD patients showed higher frontoparietal connectivity in cognitive networks compared to healthy controls, irrespective of medication status, but dopaminergic treatment specifically promoted SN-DM hyperconnectivity.