Related Experiment Video
Updated: Apr 14, 2026
Identification of Disease-related Spatial Covariance Patterns using Neuroimaging Data
Published on: June 26, 2013
Distinct patterns of spontaneous brain activity in mild cognitive impairment patients stratified by cerebrospinal
Wenzhang Qi1, Changbao Zhang2, Yuchen Feng3
1Department of Radiology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
Background:
This study aimed to explore the alterations in the Amplitude of Low-Frequency Fluctuation (ALFF) among mild cognitive impairment (MCI) patients with varying cerebrospinal fluid (CSF) biomarker levels, including abnormal Amyloid-beta (Aβ42) and phosphorylated tau protein (p-tau) (A + T +), abnormal Aβ42 and normal p-tau (A + T-), and normal Aβ42 and p-tau (A-T-), and to investigate their longitudinal changes.
Methods:
A total of 134 MCI patients were enrolled in this study and stratified into three groups, including 54 A-T- group, 28 A + T- group, and 52 A + T + group based on CSF Aβ and p-tau levels. The baseline ALFF values derived from blood oxygen level-dependent signals were employed to quantify spontaneous brain activity patterns. Comparisons were made among the three groups regarding ALFF differences, and their correlations with cognitive functions and CSF biomarkers were investigated. Additionally, a subset of participants with 2-year follow-up data underwent a mixed-effects model analysis to examine group-by-time interactions in ALFF.
Results:
At baseline, compared to the A-T- group, the A + T- group showed decreased ALFF in the bilateral cerebellar posterior lobe (CPL) and increased ALFF in the bilateral middle frontal gyrus (MFG), while the A + T + group displayed decreased ALFF in the bilateral CPL. In contrast to the A + T- group, the A + T + group exhibited decreased ALFF in the bilateral MFG. Additionally, there was a significant negative correlation between the bilateral MFG and p-tau levels, while the left MFG was positively correlated with RAVLT-learning performance, and the right MFGs was positively correlated with Aβ levels. Longitudinally, a significant group-by-time interaction was observed in the right inferior temporal gyrus (ITG), where A + T + patients exhibited a more pronounced ALFF decline over 2 years compared to A + T- patients.
Conclusion:
This study highlights distinct and evolving patterns of brain activity associated with Aβ and tau pathology in MCI. The combination of cross-sectional and longitudinal analyses reveals that tau pathology may drive accelerated functional decline in specific brain regions, particularly the right ITG, offering insights into the progression of AD-spectrum disorders.
Insights
Mild cognitive impairment (MCI) patients show distinct brain activity changes based on amyloid-beta and tau levels. Tau pathology may accelerate functional decline in specific brain regions over time.
Area of Science:
- Neuroscience
- Biomarker Research
- Cognitive Science
Background:
- Mild cognitive impairment (MCI) is characterized by changes in brain activity.
- Cerebrospinal fluid (CSF) biomarkers, including amyloid-beta (Aβ) and phosphorylated tau protein (p-tau), are crucial for classifying MCI subtypes.
- Understanding the relationship between these biomarkers and brain activity patterns is essential for tracking disease progression.
Purpose of the Study:
- To investigate alterations in the Amplitude of Low-Frequency Fluctuation (ALFF) in MCI patients with different CSF biomarker profiles.
- To examine the longitudinal changes in ALFF and their correlation with cognitive function and biomarkers.
- To differentiate brain activity patterns associated with specific Alzheimer's disease pathologies.
Main Methods:
- 134 MCI patients were categorized into three groups based on CSF Aβ and p-tau levels: A-T-, A+T-, and A+T+.
- Baseline ALFF values were measured to quantify spontaneous brain activity.
- Cross-sectional and longitudinal analyses (2-year follow-up) were performed using mixed-effects models.
Main Results:
- Baseline ALFF differences were observed in the cerebellar posterior lobe (CPL) and middle frontal gyrus (MFG) across groups.
- The A+T+ group showed decreased ALFF in the bilateral MFG compared to the A+T- group.
- Longitudinal analysis revealed a significant decline in ALFF in the right inferior temporal gyrus (ITG) in the A+T+ group over two years.
Conclusions:
- Distinct and evolving brain activity patterns are associated with Aβ and tau pathology in MCI.
- Tau pathology appears to drive accelerated functional decline in specific regions like the right ITG.
- These findings offer insights into the progression of Alzheimer's disease spectrum disorders.
