Dysfunction of the Default Mode Network in Drug-Naïve Parkinson’s Disease with Mild Cognitive Impairments: A Resting-State fMRI Study

Abstract

Objective: Cognitive impairments are common in Parkinson’s disease (PD) and can even occur in the early stages. The default mode network (DMN) is highly relevant for cognitive processes; however, it remains largely unknown if changes in the DMN connectivity are related to the cognitive decline in drug-naïve early stage PD patients with a mild cognitive impairment (MCI). This study used resting-state functional MRI (fMRI) to explore the brain connectivity of the DMN in early stage drug-naïve PD patients with MCI.Method: We recruited 32 early stage drug-naïve PD patients and 22 matched healthy controls (HC). Among the PD patients, 14 were classified as having MCI (PD-MCI) and 18 were classified as having unimpaired cognition (PD-CU). The functional integration of the DMN was evaluated by a seed-based correlation approach.Results: The brain connectivity analysis revealed reduced functional connectivity (FC) in both PD subgroups compared with HC. The PD-MCI group showed a significant reduction in FC between the DMN and a set of regions, including the precentral gyrus, middle temporal gyrus, insula, anterior inferior parietal lobule and middle frontal gyrus. Compared to the PD-CU group, the PD-MCI group demonstrated a significantly decreased FC in the middle frontal and middle temporal gyri. Additionally, compared to HC, the PD-MCI group had a significantly decreased FC within the DMN, mainly in the FC between the hippocampal formation and inferior frontal gyrus, between the posterior cingulate cortex and posterior inferior parietal lobule, and between the anterior temporal lobe and inferior frontal gyrus. Compared to the PD-CU group, the only significantly decreased FC within the DMN in the PD-MCI group was between the anterior temporal lobe and inferior frontal gyrus. In all PD patients, the decreased FC between anterior temporal lobe and middle temporal gyrus was positively correlated with attention/working performance, and the reduced FC between the hippocampal formation and inferior frontal gyrus was also positively correlated with memory function.Conclusion: Our findings suggest that an altered DMN connectivity characterizes PD-MCI patients. These findings may be helpful for facilitating the further understanding of the potential mechanisms underlying MCI in PD. However, our results are preliminary, and further investigation is needed.

Multidelay multiparametric arterial spin labeling perfusion MRI and mild cognitive impairment in early stage Parkinson's disease

“…The SMG is also part of the inferior parietal lobe, the core brain region of the default mode network, which is highly relevant for cognitive processes (Raichle et al, ). Previous structural and functional studies found cortical thinning and reduced functional connectivity in the inferior parietal lobe in PD‐MCI (Hou et al, ; Pereira et al, ). Our results align with the pattern of posterior hypoperfusion and hypometabolism characterized by prolonged ATT and decreased CBF in PD, PD‐MCI, and PD‐D previously detected by ASL, SPECT, and PET studies (Al‐Bachari et al, ; Al‐Bachari et al, ; Eckert, Tang, & Eidelberg, ; Lin et al, ; Melzer et al, ; Nobili et al, ; Pappata et al, ; Syrimi et al, ), which can be assumed to contribute to impaired cognition.…”

“…The SMG is also part of the inferior parietal lobe, the core brain region of the default mode network, which is highly relevant for cognitive processes (Raichle et al, 2001). Previous structural and functional studies found cortical thinning and reduced functional connectivity in the inferior parietal lobe in PD-MCI (Hou et al, 2016;Pereira et al, 2014). Melzer et al, 2011;Nobili et al, 2009;Pappata et al, 2011;Syrimi et al, 2017), which can be assumed to contribute to impaired cognition.…”

Abnormal Spontaneous Brain Activity in Early Parkinson’s Disease With Mild Cognitive Impairment: A Resting-State fMRI Study

“…Recently, several studies have reported a range of abnormal brain areas that are associated with cognitive decline in PD. For example, R-fMRI functional connectivity analysis has suggested patients of PD with MCI could be characterized by dysfunction in the default mode network and dorsal attention network ( Baggio et al, 2015 ; Hou et al, 2016 ). A longitudinal study using task-fMRI has reported reduction of BOLD signals that are related to working-memory brain activity in the right fusiform gyrus and right vermis in patients of PD with MCI ( Ekman et al, 2014 ).…”

Visuospatial n-back test for early detection of mild cognitive impairment in patients with Parkinson’s Disease : an fMRI study

“…A structural MRI study reported that, compared with PD-CN, patients with PD-MCI had more severe cortical thinning in the frontal and temporo-parietal cortices [21]. One study of de novo, newly diagnosed PD, which incorporated brain connectivity analysis of resting-state fMRI, revealed that patients with PD-MCI showed decreased functional connectivity between posterior cingulate cortex and posterior IPL [22].…”