Vascular risk factors and astrocytic marker for the glymphatic system activity

Yi-Chia Wei; Chih-Chin Heather Hsu; Wen-Yi Huang; Chemin Lin; Chih-Ken Chen; Yao-Liang Chen; Pin-Yuan Chen; Yu-Chiau Shyu; Ching-Po Lin

doi:10.1007/s11547-023-01675-w

Vascular risk factors and astrocytic marker for the glymphatic system activity

Radiol Med. 2023 Sep;128(9):1148-1161. doi: 10.1007/s11547-023-01675-w. Epub 2023 Jul 18.

Authors

Yi-Chia Wei^#^{1

2

3

4}, Chih-Chin Heather Hsu^#^{5

6}, Wen-Yi Huang^{7

8

9}, Chemin Lin^{8

9

10}, Chih-Ken Chen^{8

9

10}, Yao-Liang Chen^{11

12}, Pin-Yuan Chen^{8

9

13}, Yu-Chiau Shyu^{8

14}, Ching-Po Lin^{15

16}

Affiliations

¹ Department of Neurology, Chang Gung Memorial Hospital, Keelung, Taiwan. yichiawei@gmail.com.
² Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan. yichiawei@gmail.com.
³ Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan. yichiawei@gmail.com.
⁴ College of Medicine, Chang Gung University, Taoyuan, Taiwan. yichiawei@gmail.com.
⁵ Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁶ Center of Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan.
⁷ Department of Neurology, Chang Gung Memorial Hospital, Keelung, Taiwan.
⁸ Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.
⁹ College of Medicine, Chang Gung University, Taoyuan, Taiwan.
¹⁰ Department of Psychiatry, Chang Gung Memorial Hospital, Keelung, Taiwan.
¹¹ Department of Radiology, Chang Gung Memorial Hospital, Keelung, Taiwan.
¹² Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.
¹³ Department of Neurosurgery, Chang Gung Memorial Hospital, Keelung, Taiwan.
¹⁴ Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
¹⁵ Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan. chingpolin@gmail.com.
¹⁶ Department of Education and Research, Taipei City Hospital, Taipei, Taiwan. chingpolin@gmail.com.

^# Contributed equally.

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.

Keywords: Astrocyte; DTI-ALPS; Diffusion tensor imaging; GFAP; Glymphatic system.

MeSH terms

Aged
Astrocytes
Brain
Diffusion Tensor Imaging
Glymphatic System* / diagnostic imaging
Humans
Risk Factors

Abstract

MeSH terms

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