Vascular risk factors and astrocytic marker for the glymphatic system activity

• Published in: Radiologia medica Vol. 128; no. 9; pp. 1148 - 1161
• Main Authors: Wei, Yi-Chia, Hsu, Chih-Chin Heather, Huang, Wen-Yi, Lin, Chemin, Chen, Chih-Ken, Chen, Yao-Liang, Chen, Pin-Yuan, Shyu, Yu-Chiau, Lin, Ching-Po
• Format: Journal Article
• Language: English
• Published: Milan Springer Milan 01.09.2023; Springer Nature B.V
• Subjects: Atherosclerosis; Biomarkers; Blood; Body size; Brain; Cognition; Correlation analysis; Creatinine; Density; Diabetes mellitus; Diagnostic Radiology; Imaging; Interventional Radiology; Lipids; Magnetic Resonance Imaging; Medicine; Medicine & Public Health; Metabolic disorders; Metabolism; Neuroradiology; Radiology; Tensors; Ultrasound; Glymphatic system; Astrocyte; DTI-ALPS; GFAP; Diffusion tensor imaging
• ISSN: 1826-6983; 0033-8362; 1826-6983
• DOI: 10.1007/s11547-023-01675-w

Objectives Glymphatic system maintains brain fluid circulation via active transportation of astrocytic aquaporin-4 in perivascular space. The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) is an established method measuring perivascular glymphatic activity, but comprehensive investigations into its influential factors are lacking. Methods Community-dwelling older adults underwent brain MRI scans, neuropsychiatric, and multi-domain assessments. Blood biomarker tests included glial fibrillary acidic protein (GFAP) for astrocyte injury. Results In 71 enrolled participants, the DTI-ALPS index was associated with modifiable factors, including lipid profile (high-density lipoprotein, r  = 0.396; very-low-density lipoprotein, r  =  − 0.342), glucose intolerance (diabetes mellitus, standardized mean difference (SMD) = 0.7662; glycated hemoglobin, r  =  − 0.324), obesity (body mass index, r  =  − 0.295; waist, r  =  − 0.455), metabolic syndrome (SMD =   − 0.6068), cigarette-smoking (SMD =  − 0.6292), and renal clearance (creatinine, r  =  − 0.387; blood urea nitrogen, r  =  − 0.303). Unmodifiable associative factors of DTI-ALPS were age ( r  =  − 0.434) and sex (SMD = 1.0769) (all p  < 0.05). A correlation of DTI-ALPS and blood GFAP was noticed ( r  =  − 0.201, one-tailed t-test for the assumption that astrocytic injury impaired glymphatic activity, p  = 0.046). Their cognitive correlations diverged, domain-specific for DTI-ALPS (Facial Memory Test, r  = 0.272, p  = 0.022) but global cognition-related for blood GFAP (MoCA, r  =  − 0.264, p  = 0.026; ADAS-cog, r  = 0.304, p  = 0.010). Conclusion This correlation analysis revealed multiple modifiable and unmodifiable association factors to the glymphatic image marker. The DTI-ALPS index correlated with various metabolic factors that are known to increase the risk of vascular diseases such as atherosclerosis. Furthermore, the DTI-ALPS index was associated with renal indices, and this connection might be a link of water regulation between the two systems. In addition, the astrocytic biomarker, plasma GFAP, might be a potential marker of the glymphatic system; however, more research is needed to confirm its effectiveness.