Visualization of the Glymphatic System Through Brain Magnetic Resonance in Human Subjects with Neurodegenerative Disorders: A Systematic Review and Meta-Analysis

Abstract

Background: One of the major contributors to homeostasis at the level of the central nervous system, specifically the brain, is the glymphatic system, which is described as an exchange occurring at the level of and between the interstitial fluid and cerebrospinal fluid that has been linked to neurodegenerative processes. Methods: Fourteen studies were included after PROSPERO registration and a literature search. Screening, reviewing, and data extraction were performed by two reviewers. Quality assessment scales were used. General continuous and subgroup analysis, heterogeneity tests, and random effect models were run using SPSS. Forest plots were constructed based on subgroup analysis. Results: Significant correlations (p < 0.05) were detected between MRI indices and outcomes quantifying neurodegenerative diseases. Studies on Alzheimer's disease showed a positive correlation between diffusivity indices and cognitive scores. Studies on Parkinson's disease showed negative correlations between diffusivity indices and disease severity, progression, and motor function (p < 0.05). As for other conditions, the conclusions remain uncertain, yet positive results were detected (p < 0.05). Conclusions: Positive significant correlations were deduced between the ALPS index and cognitive scores, indicating that low cognition is correlated with a low ALPS index and enlarged PVSs. Negative significant correlations were deduced between ALPS indices and UPDRS scores, indicating motor dysfunction is correlated with lower ALPS indices and enlarged PVSs. Finally, MRI parameters may help to deduce disease progression across subgroups. Despite the presence of heterogeneity between studies, significant correlations with moderate to large effect sizes were detected. Glymphatic dysfunction measured through MRI indices is correlated with neurodegenerative changes across various neurological conditions.

Keywords: ALPS; MRI; brain; glymphatic system; lymphatic drainage; neurodegeneration.

Figure 1

PRISMA flowchart of the study selection process (n = 14).

Figure 2

Heatmap graph and overall score of QUADAS of the included studies (n = 14) [12,16,17,18,19,20,21,22,23,24,25,26,27,28].

Figure 3

Distribution of r and p-values across included studies, where p-values are demonstrated in the bar chart to the left (n = 11) [12,16,17,18,19,20,21,22,25,26,27].

Figure 4

Forest plot of Pearson’s coefficient of studies based on pathology type [12,16,17,19,20,21,22,25,26,27].