Multimodal assessment of brain fluid clearance is associated with amyloid-beta deposition in humans

Purpose: The present study investigates a multimodal imaging assessment of glymphatic function and its association with brain amyloid-beta deposition. Methods: Two brain CSF clearance measures (vCSF and DTI-ALPS) were derived from dynamic PET and MR diffusion tensor imaging (DTI) for 50 subjects, 24/50 were A beta positive (A beta+). T1W, T2W, DTI, T2FLAIR, and C-11-PiB and F-18-MK-6240 PET were acquired. Multivariate linear regression models were assessed with both vCSF and DTI-ALPS as independent variables and brain A beta as the dependent variable. Three types of models were evaluated, including the vCSF-only model, the ALPS-only model and the vCSF+ALPS combined model. Models were applied to the whole group, and A beta subgroups. All analyses were controlled for age, gender, and intracranial volume. Results: Sample demographics (N=50) include 20 males and 30 females with a mean age of 69.30 (sd=8.55). Our results show that the combination of vCSF and ALPS associates with A beta deposition (p < 0.05, R-2 = 0.575) better than either vCSF (p < 0.05, R-2 = 0.431) or ALPS (p < 0.05, R-2 = 0.372) alone in the A beta+ group. We observed similar results in whole-group analyses (combined model: p < 0.05, R-2 = 0.287; vCSF model: p <0.05, R-2 = 0.175; ALPS model: p < 0.05, R-2 = 0.196) with less significance. Our data also showed that vCSF has higher correlation (r = -0.548) in subjects with mild A beta deposition and DTI-ALPS has higher correlation (r=-0.451) with severe A beta deposition subjects. Conclusion: The regression model with both vCSF and DTI-ALPS is better associated with brain A beta deposition. These two independent brain clearance measures may better explain the variation in A beta deposition than either term individually. Our results suggest that vCSF and DTI-ALPS reflect complementary aspects of brain clearance functions. (c) 2023 Elsevier Masson SAS. All rights reserved.