Author Response: Association of Sleep, Neuropsychological Performance, and Gray Matter Volume With Glymphatic Function in Community-Dwelling Older Adults

We appreciate the insightful comments on our study.¹ Contrast-based imaging allows direct visualization of the glymphatic system and assessment of its function based on the pharmacokinetics of contrast agents. However, quantifications of glymphatic activity in individual fluid compartments may require other techniques.

Expanding research has shown the potential of the diffusion tensor imaging along the perivascular space (DTI-ALPS) index in reflecting glymphatic function. A search in PubMed revealed about 40 articles on this topic, including studies on Parkinson disease, small vessel disease, sleep disorders, and so forth. More studies are needed to establish the relationship between the DTI-ALPS index and glymphatic function in different regions of the brain.

With the typical resolution of diffusion MRI, any parameters derived from DTI are likely to reflect the result of partial volume averaging of the water motion in different compartments of biological tissues. The DTI-ALPS index incorporates the projection area (Dyyproj) and association area (Dzzassoc) into the denominator, potentially normalizing the effect of cell rarefaction or edema.² Although the anatomy of human medullary veins has been well described,³ future studies may consider applying susceptibility-weighted imaging to better determine the venous orientation.

We agree that further validation of existing techniques can better clarify the strengths and weaknesses of each tool, which is important when studying the human glymphatic system.