Core-Centered Connection Abnormalities Associated with Pathological Features Mediate the Progress of Cognitive Impairments in Alzheimer's Disease Spectrum Patients

Background: Abnormal default mode network (DMN) was associated with the progress of Alzheimer's disease (AD). Rather than treat the DMN as a unitary network, it can be further divided into three subsystems with different functions. Objective: It remains unclear the interactions of DMN subsystems associated with the progress of cognitive impairments and AD pathological features. Methods: This study has recruited 187 participants, including test data and verification data. Firstly, an imaging analysis approach was utilized to investigate disease-related differences in the interactions of DMN subsystems in test data (n = 149), including 42 cognitively normal subjects, 43 early mild cognitive impairment (EMCI), 32 late mild cognitive impairment (LMCI), and 32 AD patients. Brain-behavior-pathological relationships regarding to the interactions among DMN subsystems were then further examined. Secondly, DMN subsystems abnormalities for classifying AD spectrum population in the independent verification data (n = 38). Results: This study found that the impaired cognition relates to disturbances in the interactions between DMN subsystems but preferentially in core subsystem, and the abnormal regulatory processes of core subsystem were significantly associated with the levels of cerebrospinal fluid A beta and tau in AD-spectrum patients. Meantime, the nonlinear relationship between dysfunctional core subsystem and impaired cognition was observed as one progresses through the stages of MCI to AD. Importantly, this classification presented a higher sensitivity and specificity dependent on the core-centered connection abnormalities. Conclusion: The abnormal interaction patterns of DMN subsystems at an early stage of AD appeared and presented as core-centered connection abnormalities, which were the potential neuroimaging features for monitoring the development of AD.

Automated summary

The study found that abnormal interaction patterns of DMN subsystems in the early stages of AD appeared as core-centered connection abnormalities, which may serve as potential neuroimaging features for monitoring the development of AD. The impaired cognition was found to be related to disturbances in the interactions between DMN subsystems, particularly in the core subsystem. Additionally, the abnormal regulatory processes of the core subsystem were significantly associated with the levels of cerebrospinal fluid A beta and tau in AD-spectrum patients.