Abstract
BackgroundAlthough cognitive deficit is a common non-motor symptom of Parkinson’s disease (PD), the mechanism and valid biomarkers of it have not been identified. To our best knowledge, this was the first study to investigate the intrinsic dysconnectivity pattern of whole-brain functional networks in early-stage drug-naive (ESDN) PD patients and its association with cognitive deficit of PD using voxel-wise Degree Centrality (DC) approach.MethodsA total of 53 ESDN PD patients and 53 healthy controls (HC) were recruited. Resting-state fMRI (rs-fMRI) data were acquired, and voxel-wise DC approach was applied. Electrophysiological testing at P300 amplitude was recorded. The Montreal Cognitive Assessment (MoCA) was conducted to evaluate cognitive performance.ResultsESDN PD patients had lower MoCA scores and P300 amplitudes, but higher P300 latency, than HC (all p < 0.0001). PD patients displayed higher DC in the right inferior frontal gyrus (IFG), left medial frontal gyrus (MFG) and left precentral gyrus (PreCG); but lower DC in the left inferior parietal lobule (IPL), left inferior temporal gyrus (ITG), right occipital lobe, and right postcentral gyrus (PoCG) (pBonferroni correction < 0.0001). Interestingly, the DC values of left MFG, right PoCG and right occipital lobe were negatively associated with P300 latency but positively associated with P300 amplitudes and MoCA scores (all pBonferroni correction < 0.0001).ConclusionsOur results indicate the cognitive deficit and abnormal intrinsic brain functional network in ESDN PD patients. The damage of Default Mode Network (DMN) may be contributes to the pathogenesis of cognitive dysfunction in ESDN PD.
Highlights
Cognitive deficit is a common, non-motor symptom in the early to moderate stages of Parkinson’s disease (PD) (Aarsland et al, 2009), even in newly diagnosed PD patients without exposure to medication (Janvin et al, 2006; Aarsland et al, 2009)
The inclusion criteria was as follows: (1) met the UK PD Society Brain Bank Criteria; (2) illness duration was less than 2 years, and Hoehn and Yahr (H&Y) stage ≤ 2 at baseline; (3) did not receive any anti-PD or antidepressant medications before functional magnetic resonance imaging (fMRI) scans; (4) without any apparent cognitive impairment [Mini-Mental State Examination (MMSE) scores > 24] and were right-handed; All subjects were free of dementia according to their MMSE scores; and (5) All subjects did not met the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition criteria for depression/anxiety disorder, who were diagnosed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition and Hamilton Anxiety Rating Scale (HAMA) scale and HAMD scores
The main results of this study were as follows: (1) Montreal Cognitive Assessment (MoCA) score and P300 amplitude decreased and latency prolonged in PD patients compared with healthy controls (HC); (2) PD patients had higher Degree Centrality (DC) values in the left medial frontal gyrus (MFG), right inferior frontal gyrus (IFG), and left precentral gyrus (PreCG), but lower DC values in the left inferior parietal lobule (IPL), left inferior temporal gyrus (ITG), right occipital lobe, and right postcentral gyrus (PoCG) compared to HC; and (3) the DC values of left MFG, right PoCG, and right occipital lobe were negatively associated with P300 latency, but positively associated with P300 amplitudes and MoCA scores in PD patients
Summary
Cognitive deficit is a common, non-motor symptom in the early to moderate stages of Parkinson’s disease (PD) (Aarsland et al, 2009), even in newly diagnosed PD patients without exposure to medication (Janvin et al, 2006; Aarsland et al, 2009). The incidence of cognitive deficit in early-stage, drugnaive (ESDN) PD patients is twice as high as that of the general population’s control subjects (Aarsland et al, 2009). It is important to identify cognitive deficit of PD patients early. Cognitive deficit is a common non-motor symptom of Parkinson’s disease (PD), the mechanism and valid biomarkers of it have not been identified. This was the first study to investigate the intrinsic dysconnectivity pattern of whole-brain functional networks in early-stage drug-naive (ESDN) PD patients and its association with cognitive deficit of PD using voxel-wise Degree Centrality (DC) approach
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