Abstract
Cognitive impairment is a common non-motor feature of Parkinson's disease (PD). Understanding the neural mechanisms of this deficit is crucial for the development of efficient methods for treatment monitoring and augmentation of cognitive functions in PD patients. The current study aimed to investigate resting state fMRI correlates of cognitive impairment in PD from a large-scale network perspective, and to assess the impact of dopamine deficiency on these networks. Thirty PD patients with resting state fMRI were included from the Parkinson's Progression Marker Initiative (PPMI) database. Eighteen patients from this sample were also scanned with 123I-FP-CIT SPECT. A standardized neuropsychological battery was administered, evaluating verbal memory, visuospatial, and executive cognitive domains. Image preprocessing was performed using an SPM8-based workflow, obtaining time-series from 90 regions-of-interest (ROIs) defined from the AAL brain atlas. The Brain Connectivity Toolbox (BCT) was used to extract nodal strength from all ROIs, and modularity of the cognitive circuitry determined using the meta-analytical software Neurosynth. Brain-behavior covariance patterns between cognitive functions and nodal strength were estimated using Partial Least Squares. Extracted latent variable (LV) scores were matched with the performances in the three cognitive domains (memory, visuospatial, and executive) and striatal dopamine transporter binding ratios (SBR) using linear modeling. Finally, influence of nigrostriatal dopaminergic deficiency on the modularity of the “cognitive network” was analyzed. For the range of deficits studied, better executive performance was associated with increased dorsal fronto-parietal cortical processing and inhibited subcortical and primary sensory involvement. This profile was also characterized by a relative preservation of nigrostriatal dopaminergic function. The profile associated with better memory performance correlated with increased prefronto-limbic processing, and was not associated with presynaptic striatal dopamine uptake. SBR ratios were negatively correlated with modularity of the “cognitive network,” suggesting integrative effects of the preserved nigrostriatal dopamine system on this circuitry.
Highlights
Cognitive impairment is a very important and common nonmotor feature of Parkinson’s disease (PD) with a major impact on patients’ and caregivers’ quality of life, as well as healthcare costs (Muslimovic et al, 2005; Vossius et al, 2011; Svenningsson et al, 2012)
The data were representative of the entire DaTSCAN cohort of PD patients
Higher executive functional scores were associated with higher nodal strength of dorsal cortical nodes and lower involvement of subcortical, occipital, temporal, and ventral cortical nodes, suggesting that relative preservation of executive functions in PD is linked to the dominance of dorsal cortical processing with inhibition of subcortical, paralimbic, and primary sensory circuitry when the subject is at resting state with eyes open
Summary
Cognitive impairment is a very important and common nonmotor feature of Parkinson’s disease (PD) with a major impact on patients’ and caregivers’ quality of life, as well as healthcare costs (Muslimovic et al, 2005; Vossius et al, 2011; Svenningsson et al, 2012). One-fifth of newly diagnosed PD patients fulfill clinical criteria for mild cognitive impairment (PD-MCI) (Aarsland et al, 2009) and about one-sixth develop dementia after 5 years (Williams-Gray et al, 2009). There is strong evidence suggesting that the impairment of at least 3 major dopaminergic pathways (nigrostriatal, mesocortical, mesolimbic) originating in the brainstem play a very important role in cognitive dysfunction associated with PD (Narayanan et al, 2013). Numerous studies on cognitive dysfunction associated with PD have revealed structural and functional abnormalities within the Frontiers in Systems Neuroscience www.frontiersin.org
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