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Updated: Apr 14, 2026

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
Published on: August 7, 2017
Relation between subcortical grey matter atrophy and conversion from mild cognitive impairment to Alzheimer's disease
Hyon-Ah Yi1, Christiane Möller2, Nikki Dieleman3
1Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Neurology, Keimyung University School of Medicine, Daegu, South Korea.
Objective:
To investigate whether subcortical grey matter atrophy predicts progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD), and to compare subcortical volumes between AD, MCI and controls. To assess the correlation between subcortical grey matter volumes and severity of cognitive impairment.
Methods:
We included 773 participants with three-dimensional T1-weighted MRI at 3 T, made up of 181 controls, who had subjective memory symptoms with normal cognition, 201 MCIs and 391 AD. During follow-up (2.0 ± 0.9 years), 35 MCIs converted to AD (progressive MCI) and 160 MCIs remained stable (stable MCI). We segmented volumes of six subcortical structures of the amygdala, thalamus, caudate nucleus, putamen, globus pallidus and nucleus accumbens, and of the hippocampus, using FMRIBs integrated registration and segmentation tool.
Results:
Analysis of variances, adjusted for sex and age, showed that all structures, except the globus pallidus, were smaller in AD than in controls. In addition, the amygdala, thalamus, putamen, nucleus accumbens and hippocampus were smaller in MCIs than in controls. Across groups, all subcortical greymatter volumes, except the globus pallidus, showed a positive correlation with cognitive function, as measured by Mini Mental State Examination (MMSE) (0.16
Conclusions:
In addition to the hippocampus, the nucleus accumbens volume loss was also associated with increased risk of progression from MCI to AD. Furthermore, volume loss of subcortical grey matter structures was associated with severity of cognitive impairment.
Insights
Subcortical grey matter atrophy, particularly in the nucleus accumbens and hippocampus, predicts progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Volume loss in these areas also correlates with cognitive impairment severity.
Area of Science:
- Neuroimaging
- Neurodegeneration
- Alzheimer's Disease Research
Background:
- Subcortical grey matter atrophy is implicated in cognitive decline.
- Predicting progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is crucial for early intervention.
Purpose of the Study:
- To determine if subcortical grey matter atrophy predicts MCI to AD progression.
- To compare subcortical volumes across AD, MCI, and control groups.
- To assess the relationship between subcortical volumes and cognitive impairment severity.
Main Methods:
- Utilized 3D T1-weighted MRI scans from 773 participants (181 controls, 201 MCI, 391 AD).
- Segmented volumes of amygdala, thalamus, caudate nucleus, putamen, globus pallidus, nucleus accumbens, and hippocampus.
- Followed up participants for 2.0 ± 0.9 years to track MCI to AD conversion.
Main Results:
- AD patients showed smaller volumes in most subcortical structures compared to controls.
- MCI patients had smaller amygdala, thalamus, putamen, nucleus accumbens, and hippocampus volumes than controls.
- Smaller hippocampus and nucleus accumbens volumes were associated with increased risk of MCI to AD progression.
- Subcortical grey matter volumes correlated positively with cognitive function (MMSE scores).
Conclusions:
- Nucleus accumbens and hippocampus volume loss are significant predictors of MCI to AD progression.
- Subcortical grey matter atrophy is linked to the severity of cognitive impairment.
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