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Updated: Jan 19, 2026
Modeling the Functional Network for Spatial Navigation in the Human Brain
Published on: October 13, 2023
Amyloid and cerebrovascular burden divergently influence brain functional network changes over time
Joanna Su Xian Chong1, Hyemin Jang1, Hee Jin Kim1
1From the Centre for Cognitive Neuroscience (J.S.X.C., K.K.N., J.Z.), Neuroscience and Behavioural Disorders Programme, Duke-National University of Singapore Medical School; Department of Neurology (H.J., H.J.K., D.L.N., S.W.S.), Samsung Medical Center, Sungkyunkwan University School of Medicine; Department of Neurology (J.H.L.), Asan Medical Center, Ulsan University School of Medicine, Seoul, Korea; and Clinical Imaging Research Centre, National University of Singapore (J.Z.).
Objective:
To examine the effects of baseline Alzheimer disease and cerebrovascular disease markers on longitudinal default mode network (DMN) and executive control network (ECN) functional connectivity (FC) changes in mild cognitive impairment (MCI).
Methods:
We studied 30 patients with amnestic MCI (aMCI) and 55 patients with subcortical vascular MCI (svMCI) with baseline Pittsburgh Compound B (PiB)-PET scans and longitudinal MRI scans. Participants were followed up clinically with annual MRI for up to 4 years (aMCI: 26 with 2 timepoints, 4 with 3 timepoints; svMCI: 13 with 2 timepoints, 16 with 3 timepoints, 26 with 4 timepoints).
Results:
β-Amyloid (Aβ) burden was associated with longitudinal DMN FC declines, while cerebrovascular burden was associated with longitudinal ECN FC changes. When patients were divided into PiB+ and PiB- groups, PiB+ patients showed longitudinal DMN FC declines, while patients with svMCI showed longitudinal ECN FC increases. Direct comparisons between the 2 groups without mixed pathology (aMCI PiB+ and svMCI PiB-) recapitulated this divergent pattern: aMCI PiB+ patients showed steeper longitudinal DMN FC declines, while svMCI PiB- patients showed steeper longitudinal ECN FC increases. Finally, using baseline PiB uptake and lacune numbers as continuous variables, baseline PiB uptake showed inverse U-shape associations with longitudinal DMN FC changes in both MCI subtypes, while baseline lacune numbers showed mainly inverse U-shape relationships with longitudinal ECN FC changes in patients with svMCI.
Conclusions:
Our findings underscore the divergent effects of Aβ and cerebrovascular burden on longitudinal FC changes in the DMN and ECN in the predementia stage, which reflect the underlying pathology and may be used to track early changes in Alzheimer disease and cerebrovascular disease.
Insights
Alzheimer disease markers impact default mode network (DMN) connectivity, while cerebrovascular markers affect executive control network (ECN) connectivity in mild cognitive impairment (MCI). These findings help track early neurodegenerative changes.
Area of Science:
- Neuroimaging
- Neurodegenerative Diseases
- Brain Connectivity
Background:
- Mild cognitive impairment (MCI) precedes dementia and is characterized by cognitive decline.
- Understanding the distinct pathological impacts on brain networks is crucial for early diagnosis and intervention.
- Alzheimer disease (AD) and cerebrovascular disease (CVD) are common comorbidities in MCI.
Purpose of the Study:
- To investigate how baseline Alzheimer disease (AD) markers (amyloid-beta burden) and cerebrovascular disease (CVD) markers influence longitudinal changes in functional connectivity (FC) within the default mode network (DMN) and executive control network (ECN) in individuals with MCI.
- To differentiate the effects of AD pathology versus CVD on DMN and ECN FC trajectories.
Main Methods:
- Longitudinal study of 30 amnestic MCI (aMCI) and 55 subcortical vascular MCI (svMCI) patients.
- Baseline Pittsburgh Compound B (PiB)-PET scans for amyloid-beta (Aβ) burden assessment.
- Longitudinal MRI scans for functional connectivity (FC) analysis over up to 4 years.
- Clinical follow-up and assessment of cerebrovascular burden (lacune count).
Main Results:
- Higher Aβ burden correlated with declining DMN FC. Higher cerebrovascular burden correlated with altered ECN FC.
- PiB-positive (PiB+) MCI patients showed declining DMN FC, while svMCI patients exhibited increasing ECN FC.
- Direct comparisons revealed steeper DMN FC declines in aMCI PiB+ and steeper ECN FC increases in svMCI PiB- patients.
- Baseline Aβ and lacune counts showed complex, often inverse U-shaped, associations with longitudinal FC changes in DMN and ECN.
Conclusions:
- Baseline Aβ and cerebrovascular burden have divergent effects on longitudinal DMN and ECN FC changes in MCI.
- These distinct network alterations reflect underlying pathologies and can serve as early biomarkers for AD and CVD.
- Monitoring DMN and ECN FC changes may aid in tracking predementia progression.
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