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Related Experiment Video

Updated: Jan 7, 2026

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
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Longitudinal changes in subcortical functional connectivity during Alzheimer's disease progression.

Sunghun Kim1, Sewook Oh2, Hyunjin Park2

  • 1Department of Brain and Cognitive Engineering, Korea University, Seoul, Republic of Korea; BK21 Four Institute of Precision Public Health, Seoul, Republic of Korea.

The Journal of Prevention of Alzheimer'S Disease
|January 2, 2026
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Summary

Alzheimer's disease (AD) shows altered brain connectivity. This study tracks individual changes in subcortico-cortical functional connectivity (FC) in cognitive impairment (CI), linking it to memory and executive function decline.

Keywords:
Alzheimer’s diseaseCognitive functionFunctional connectivityLongitudinal AnalysisNormative modelingSubcortex

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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.