Relationship between impaired cerebral lymphatic function and iron deposition, blood flow in VaD: a clinical MRI
Yingqi Lu1,2, Yushuang Liu3,4, Haoran Zhang2
1Department of Rehabilitation Medicine, The People's Hospital of Baoan Shenzhen, Shenzhen, China.
Insights
Altered lymphatic function, indicated by a reduced Diffusion Tensor Imaging-based white matter tract integrity index (DTI-ALPS), is a key factor in vascular dementia (VaD). Reduced cerebral blood flow (CBF) may also contribute to cognitive deficits in VaD.
Area of Science:
- Neuroimaging
- Neurology
- Vascular Biology
Background:
- Cerebral small vessel disease (CSVD) induces complex neural changes in vascular dementia (VaD).
- Altered lymphatic function is implicated in VaD cognitive deficits, but its link to iron deposition and cerebral blood flow (CBF) is unclear.
Purpose of the Study:
- To investigate the relationship between lymphatic function (using DTI-ALPS), iron deposition (using QSM), and CBF in VaD patients.
- To explore the role of CBF and iron deposition in modulating DTI-ALPS and cognitive function.
Main Methods:
- 59 participants (30 healthy, 29 VaD) underwent QSM, ASL, and DTI scans.
- Calculated DTI-ALPS, mean susceptibility, and mean CBF for different brain regions.
- Performed correlation and mediation analyses to assess relationships between imaging markers and cognitive measurements.
Main Results:
- VaD patients showed significantly lower DTI-ALPS in all brain regions compared to controls.
- Elevated mean susceptibility was observed in the occipital lobes, and reduced mean CBF in frontal and insular regions of VaD patients.
- Reduced DTI-ALPS and increased susceptibility correlated with cognitive impairments; CBF appeared to modulate DTI-ALPS.
Conclusions:
- Altered lymphatic function, reflected by DTI-ALPS, is a significant pathological factor in VaD.
- Reduced CBF may play a role in the observed lymphatic dysfunction and cognitive decline in VaD.
- These findings suggest potential therapeutic targets for VaD treatment by addressing lymphatic function and CBF.
Background:
The neural mechanisms induced by cerebral small vessel disease (CSVD) in the vascular dementia (VaD) is extremely complex. Recent studies have identified altered lymphatic function as a key factor contributing to the development of cognitive deficits, whether they linked to iron deposition and reduced cerebral blood flow remains unclear.
Methods:
The study involved 59 participants, comprising 30 healthy controls and 29 patients with VaD. Each participant underwent QSM, ASL, and DTI imaging scans and clinical measurements. The ALPS index based on DTI, QSM, and ASL for the left and right hemispheres, as well as for the whole brain were calculated and compared between groups. Regional mean susceptibility and mean CBF based on AAL template were calculated and compared between groups. Correlation analyses were performed between altered indexes and clinical measurements. Finally, mediation analyses were conducted to determine whether the mean susceptibility rate and mean CBF were involved in the modulation process of the ALPS.
Results:
DTI-ALPS based analysis demonstrated a significantly lower ALPS index for the left, right, and whole brain in the VaD as compared to healthy controls. Mean susceptibility in the bilateral superior occipital gyrus and bilateral middle occipital gyrus was significantly higher, whereas mean CBF in the eft inferior frontal gyrus, opercular part, right rolandic operculum, right insula, and right heschl gyrus was significantly lower in the VaD. Further correlation analyses revealed associations between elevated mean susceptibility, reduced ALPS index, and cognitive impairments. Additionally, the results of correlation and mediation analyses suggested that CBF may be involved in the regulatory process of DTI-ALPS.
Conclusion:
Our results demonstrated that altered lymphatic function is a key pathological factor in VaD, and reduced cerebral blood flow may play a role in this process. These findings provide a theoretical basis for identifying new targets in the treatment of VaD.
