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Updated: Apr 24, 2026
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Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
Published on: August 7, 2017
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Default mode network failure across the Alzheimer's disease spectrum
Nick Corriveau-Lecavalier1,2, Ellen Dicks1,3,4, Peter R Martin5
1Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Brain : a Journal of Neurology
|April 22, 2026
Summary
Brain network changes in Alzheimer's disease (AD) predict disease progression. Default mode network (DMN) connectivity patterns can forecast amyloid positivity, mild cognitive impairment, and dementia, even before amyloid buildup is visible.
Area of Science:
- Neuroscience
- Systems Neuroscience
- Neuroimaging
Background:
- Alzheimer's disease (AD) involves complex interactions between molecular pathology and brain network disruptions.
- Understanding these dynamics is crucial for developing effective interventions.
- Limited longitudinal data has hindered progress in modeling AD's complex systems nature.
Purpose of the Study:
- To investigate the longitudinal relationship between default mode network (DMN) subsystems and amyloid pathology in AD.
- To determine if DMN connectivity patterns predict conversion to amyloid positivity, mild cognitive impairment (MCI), and dementia.
Main Methods:
- Utilized task-free functional MRI (fMRI) and amyloid PET imaging in a large longitudinal cohort (n=1,451).
- Employed mixed-effect models to analyze DMN subsystem connectivity over time.
- Applied Cox proportional hazards models to assess predictive value of DMN connectivity for disease conversion.
Main Results:
- Revealed a dynamic interplay between amyloid accumulation and DMN subsystem connectivity, showing both increased and decreased connectivity.
- Demonstrated that DMN connectivity patterns significantly predicted conversion to MCI, dementia, and even amyloid positivity in unimpaired individuals.
- These associations remained significant independent of age, APOE4 status, sex, education, and motion.
Conclusions:
- Breakdowns in DMN feedback loops represent a core systems-level pathophysiology in AD.
- Functional dyshomeostasis within the DMN may precede detectable amyloidosis.
- Future research should focus on developing individual-level biomarkers of brain function for targeted therapies.
Keywords:
Alzheimer’s diseaseamyloiddefault mode networkfunctional magnetic resonance imagingneurologyMore Related Videos
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