Differential Connectivity Patterns of Mild Cognitive Impairment in Alzheimer's and Parkinson's Disease: A Large-scale Brain Network Study

Rationale and objectives: Cognitive disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD), significantly impact the quality of life in older adults. Mild cognitive impairment (MCI) is a critical stage for intervention and can predict the development of dementia. The causes of these two diseases are not fully understood, but there is an overlap in their neuropathology. There is a lack of direct comparison regarding the changes in functional connectivity within and between different brain networks during cognitive impairment in these two diseases.

Objective: This study aims to investigate changes in brain network connectivity of AD and PD with mild cognitive impairment, shedding light on the underlying neuropathological mechanisms and potential treatment options.

Methods: A total of 33 AD-MCI patients, 55 PD-MCI patients, and 34 healthy controls (HCs) underwent resting-state functional MRI and cognitive function assessment using Independent Components Analysis (ICA). We compared intra- and inter-network functional connectivity among the three groups and analyzed the correlation between changes in functional connectivity and cognitive domain performance.

Results: Using ICA, we identified eight functional networks. In the AD-MCI group, reductions in internetwork functional connectivity were mainly around the default mode network (DMN). Intra-network functional connectivity was widely reduced, especially in the DMN, while intra-network functional connectivity in the Salience Network (SN) increased. In contrast, in the PD-MCI group, reductions in internetwork functional connectivity were mainly around the SN. Intra-network functional connectivity in the SN decreased, while intra-network functional connectivity in other networks increased.

Conclusion: This study highlights distinct yet overlapping changes in brain network connectivity in AD and PD, providing new insights into the underlying mechanisms of cognitive impairment disorders.