Vascular risk factors and astrocytic marker for the glymphatic system activity

Abstract

Abstract 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.