Multimodal topographic properties of white matter functional segregation in Alzheimer's disease: A simultaneous
Yuying Jiao1, Tingting Zhang2, Wei Han1
1Department of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Objective:
White Matter (WM) functional networks offer insight into the network processes underlying progression along the Alzheimer's disease (AD) continuum. Amyloid (Aβ) retention in WM regions, as measured by Aβ-PET, reflects WM integrity and is associated with cognition. This study used simultaneous PET/MR imaging to investigate topographic alterations in WM functional networks and Aβ-burden networks, aiming to provide objective neuroimaging evidence of white matter-related pathology in Alzheimer's disease.
Methods:
A total of 85 subjects were included in this study, including 42 patients with AD, 24 patients with Prodromal AD (PAD), and 19 age- and sex-matched healthy controls (HC). Cognitive assessments were collected along with clinical information, including the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Every enrolled subject underwent an integrated 18F-Florbetapir (18F-AV45) PET/MR scan. High-resolution T1-weighted structural images, blood oxygen level dependent fMRI (BOLD-fMRI) and diffusion tensor imaging (DTI) data were acquired for all subjects. K-means clustering was utilized to obtain white matter functional networks (BWM) from BOLD-fMRI. Normalized Aβ standardized uptake value ratio (SUVR) was calculated within each BWM, with the whole cerebellum as the reference region. The group covariance matrix was generated by Pearson correlation to construct functional, structural, and Aβ retention networks. Topographic properties including the clustering coefficient, characteristic path length and global efficiency were calculated.
Results:
AD patients showed lower mean MMSE and MoCA scores than HC and PAD subjects (pcorrected < 0.001). In the functional network, higher characteristic path length and lower global efficiency were found in AD patients, compared with the PAD and HC groups (both p < 0.05). Higher characteristic path length and lower global efficiency were observed in the Aβ retention network of the AD group (all p < 0.05). Furthermore, the clustering coefficient was lower in AD patients (both p < 0.05). The AD group exhibited a significant difference in functional-Aβ retention coupling compared with the PAD group (p = 0.002) and the HC group (p < 0.001). No significant difference was found in the structural network.
Conclusion:
We observed cognitive impairment in AD patients as compared with participants of the HC or PAD group. AD patients also showed higher characteristic path length and lower global efficiency in both functional and Aβ retention networks. These results may highlight the importance of the multimodal topographic properties of white matter functional segregation for early diagnosis and personalized management of AD.
Insights
Alzheimer's disease (AD) patients exhibit altered white matter functional and amyloid-beta (Aβ) retention networks, characterized by reduced global efficiency and increased path length. These network changes correlate with cognitive decline, suggesting potential for early AD diagnosis.
Area of Science:
- Neuroimaging
- White Matter Integrity
- Alzheimer's Disease Pathophysiology
Background:
- White Matter (WM) functional networks are crucial for understanding Alzheimer's disease (AD) progression.
- Amyloid-beta (Aβ) deposition in WM is linked to cognitive function and WM integrity.
- Investigating WM network alterations in AD is essential for early diagnosis and treatment.
Purpose of the Study:
- To investigate topographic alterations in WM functional and Aβ-burden networks using simultaneous PET/MR imaging.
- To provide objective neuroimaging evidence of white matter-related pathology in Alzheimer's disease.
- To explore the relationship between WM network properties, Aβ burden, and cognitive status across the AD continuum.
Main Methods:
- 85 subjects (42 AD, 24 Prodromal AD, 19 Healthy Controls) underwent integrated 18F-Florbetapir (18F-AV45) PET/MR scans.
- White matter functional networks (BWM) were derived from BOLD-fMRI, and Aβ retention networks were constructed using Aβ-PET SUVR.
- Network properties (clustering coefficient, path length, global efficiency) and functional-Aβ coupling were analyzed.
Main Results:
- AD patients showed significantly lower cognitive scores (MMSE, MoCA) compared to HC and PAD groups.
- AD patients exhibited higher characteristic path length and lower global efficiency in both functional and Aβ retention networks.
- Significant differences in functional-Aβ retention coupling were observed in AD patients compared to PAD and HC groups.
Conclusions:
- Cognitive impairment in AD is associated with significant alterations in white matter functional and Aβ retention networks.
- Increased characteristic path length and decreased global efficiency in these networks may serve as biomarkers for AD.
- Multimodal topographic analysis of WM networks offers potential for early AD diagnosis and personalized management.
