Longitudinal changes in subcortical functional connectivity during Alzheimer's disease progression

Area of Science:

• Neuroscience
• Cognitive Science
• Medical Imaging

Background:

• Human cognition depends on integrated neural networks connecting the cortex and subcortical structures.
• Alterations in functional connectivity (FC) between cortical and subcortical regions are implicated in Alzheimer's disease (AD) symptoms.
• An individualized, longitudinal framework for subcortico-cortical FC deviations in brain aging is lacking.

Purpose of the Study:

• To develop and apply a normative modeling approach for characterizing subcortico-cortical FC trajectories across the adult lifespan.
• To quantify individual deviations in subcortico-cortical FC in individuals with cognitive impairment (CI) relative to normative aging.
• To examine the longitudinal relationship between FC changes and cognitive decline in CI.

Main Methods:

• Leveraged large-scale longitudinal neuroimaging datasets.
• Applied normative modeling to establish brain aging trajectories.
• Quantified individual FC deviations using centile scores and tracked longitudinal changes.
• Correlated FC changes with clinical measures of episodic memory, executive function, and language.

Main Results:

• Individuals with CI exhibited widespread decreases in subcortico-cortical FC, contrasting with normal aging patterns.
• The limbic network showed divergent FC patterns in CI compared to normative aging.
• These FC alterations were significantly associated with declines in memory and executive functions.

Conclusions:

• The findings advance understanding of AD-related connectopathy and provide a framework for profiling individualized FC changes in CI.
• This approach can inform individualized prognosis and targeted interventions for cognitive impairment.
• Subcortico-cortical FC deviations offer potential biomarkers for tracking disease progression and treatment response.