Objective:

To investigate the relationship between cerebrospinal fluid (CSF) flow dynamics and amyloid biomarkers in Alzheimer’s disease (AD) using low-b-value-diffusion-MRI (dMRI)–derived pseudo-diffusivity (MΨ), a novel imaging marker of pseudorandom CSF flow.

Background:

Efficient CSF circulation is essential for clearing metabolic waste, including amyloid-β (Aβ) peptides, through pathways collectively described as the glymphatic system. Impairment of CSF flow has been implicated in amyloid accumulation and neurodegeneration. However, noninvasive quantification of CSF flow dynamics remains limited in clinical research. Low b-value dMRI offers a sensitive approach to detect subtle, multidirectional CSF motion, complementing conventional diffusion measures.

Design/Methods:

Participants were drawn from the Washington University Knight Alzheimer Disease Research Center cohort. Individuals with both low-b-dMRI and CSF biomarker data were included. Voxel-wise analyses (n=312) were performed on CSF MΨ maps generated using the CSF pseudo-diffusion spatial statistics (CΨSS) workflow and harmonized across seven Siemens 3 T scanners using ComBat. Region-of-interest (ROI) analysis (n=429) was performed using eleven regions from the CSF Waterways (CWW) atlas. Associations were tested between harmonized CSF MΨ values and CSF biomarkers across CWWs using general linear models adjusted for age, sex, and brain parenchyma fraction.

Results:

Increased CSF MΨ was associated with higher CSF Aβ40, with much weaker associations observed for Aβ42 and tau. Voxel-wise analysis showed significant positive correlations between CSF MΨ and CSF Aβ40, particularly within the Sylvian fissure and ventricular CSF spaces (FWE-p<0.05). ROI-analysis confirmed widespread positive associations between harmonized CSF MΨ and CSF Aβ40 across multiple CSF compartments, with the strongest effects in CWW-7 and CWW-8 (Sylvian fissure; FDR-p<0.05).

Conclusions: