The primary objective of this study was to explore the difference of pattens of anatomical and FC in HCs, PD, and PD-MCI and the relationship between the connection strengths and cognitive state༎We found that in PD patients, brain network associated with the cognitive dysfunction was BPcu, and the FC within BPcu significantly decreased in PD-NC and PD-MCI. Furthermore, higher connectivity strength was associated with a faster information processing speed (TMTA, DSST), a better episodic memory (CFT-20 min DR) and a better general cognition (MMSE).
Rs-fMRI is a promising approach that measures naturally occurring low-frequency fluctuations in blood oxygenation level-dependent (BOLD) signals reflecting physiologically meaningful changes of spontaneous neural activity in the resting-state networks (RSNs) to investigate neuropsychiatric disorders[15]. It avoids demanding task performance and can easily obtain relatively stable results[16]. Rs-fMRI is widely used in Alzheimer's disease (AD)[17], other dementias[18] and mood disorders[15]. Mounting studies have identified a wide array of brain regions that exhibit group-wise differences between HCs and neuropsychiatric disorders[15]. Over the last decades, rs-fMRI has been carried out to investigate the FC changes in patients with PD [19–22]. However, there is still a need for understanding the exact relationship between the function and brain regions and the relationship between the connection strengths and cognitive state.
DMN is the most popular target in RSNs, including a midline core (including the anterior medial prefrontal cortex (aMPFC) and PCC) and two subsystems (the dorsal medial prefrontal cortex (DMPFC) subsystem and the medial temporal lobe (MTL) subsystem )[23]. DMN is thought to be involved in advanced cognitive functions. Early study has observed DMN dysfunction in PD patients[24]. Wolters et al. [25] observed that cognitive impairment in PD was correlated with reduced FC in networks involved in cognition, especially in the DMN. Studies suggested that the precuneus was implicated in high-level cognitive functions, including self-related processing, episodic memory, and aspects of consciousness [26–28]. Our study found that BPcu was the cognitive related region in DMN.
There is significant clinical heterogeneity in cognitive impairment in PD[29]. The prevalence of PD-MCI was 25%[29]and with the development of the disease, the cumulative prevalence of PD with dementia (PDD) gradually increases[18]. The frequency and severity of PD induced cognitive decline emphasise the need to approach this impairment as a symptom that requires separate attention. However, the mechanism of PDD is not clear yet. It is urgently need to find biomarkers or identify the risk factors or signal of PDD in early stage for improving the prognosis of the disease[30]. The PD-NC and HCs in our study showed comparable performances of cognitive function, but the FC within the cognitive-related region in the brain – BPcu in PD-NC was significantly declined compared to HCs, which might be an early signal of cognitive damage. Díez-Cirarda et al. [19] included 26 HCs, 12 PD-NC and 23 PD-MCI and found that PD-MCI group dynamic FC deteriorated but did not been observed in PD-NC.
The cognitive impairment of PD patients is mainly manifested in visual space, attention, executive function, and memory, but these clinical manifestations are not diagnostic specific[5]. Similar with the report, PD-MCI in our study showed significant worse performances in general cognition. For PD-MCI, the higher the FC values within BPcu were related to better performances information processing speed (i.e. shorter time consumed of TMTA and higher scores of DSST) and episodic memory (i.e. higher scores of CFT-20 min DR). Similar associations were also detected between the FC within BPcu and performances of MMSE for PD-NC.
There are some limitations in this study. First, this is a single center study with a limited number of patients. Also, all PD patients from this study were on medication and we cannot rule out the possibility that the drugs may have impacted the rs-fMRI. Lastly, the use of the outcomes needs to be further validated in additional populations.