Abstract
Background and Aims
The glymphatic system is a network of extracellular spaces between neurons, glial cells, and capillaries that promotes the elimination of soluble molecules from the brain. Its dysfunction is probably relevant for neurodegenerative diseases such as Alzheimer's disease (AD). It is widely accepted that cognitive impairment accompanies chronic kidney disease (CKD). CKD is also a risk factor for dementia. However, the role of the glymphatic system in this process is unknown. A recent method to study the glymphatic system in human subjects has been proposed based on Diffusion Tensor Imaging (DTI) data and water diffusion calculation along with perivascular spaces. This approach is based on calculating a diffusion index named ALPS and showed that the glymphatic flow is reduced in MCI.
Method
To analyze the role of glymphatic system in CKD patients, we took advantage of the Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI is a longitudinal multicenter study helping researchers to monitor Alzheimer's disease and Mild Cognitive Impairment (MCI) progression. This database has a cohort of control patients and MCI patients, among which several patients with CKD stage II-III were identifiable from the creatinine values. Patients with Alzheimer's disease were excluded for this study. Among the control and MCI patients, we identified 12 CKD patients and pair-matched 12 non-CKD patients comparable for age, gender, and MoCA score. Magnetic resonance data with DTI sequences were retrieved for all patients, and the glymphatic system was characterized by the ALPS index. Tensor values were calculated using the FSL software; the diffusion values were calculated on tensor images using the ImageJ software. Differences in ALPS between CKD and non-CKD patients with and without MCI were tested.
Results
Analysis of DTI data confirmed that control patients without CKD had lower ALPS values when MCI was present compared to the non-MCI patients, suggesting a reduction of water diffusion in the glymphatic system. However, the presence of CKD had a different effect: in the absence of MCI, CKD did not modify ALPS values compared to non-CKD patients. At variance, in patients with MCI, CKD resulted in a significant increase of water diffusion in the glymphatic system compared to the controls.
Conclusion
In this preliminary study, MCI and CKD exerted opposite effects on the diffusion of water within the glymphatic system: MCI was accompanied by a reduction of water diffusion whereas CKD by an increased diffusion in the glymphatic spaces.
It is possible that small modification of water balance in CKD may be responsible for the increased diffusion of water in glymphatics in CKD. Further studies are needed to verify whether this unexpected phenomenon may modify cognitive function with a mechanism rather different from Alzheimer's disease.
Drying of channels by evaporation through a permeable medium