The glymphatic system has become a key focus of interest for neurodegenerative disorders. However, establishing a reliable imaging modality for assessment has proven challenging. Recently Diffusion Tensor Imaging (DTI) has been trialled in Alzheimer’s Disease, Normal Pressure Hydrocephalus and PD. This study used DTI along the perivascular space (DTI-ALPS) to evaluate glymphatic system activity in individuals with PD, RBD, and healthy controls. In limited studies of this technology to date, higher ALPS scores have been associated with an improved glymphatic activity.

A total of 416 patients were enrolled including 168 with PD, 119 with RBD, and 129 healthy controls at a single centre. Exclusion criteria of note included those with significant cerebral parenchymal or cerebrovascular abnormalities, very low cognitive scores, and subjects with poor-quality imaging. Age and gender were matched across the groups. However, significant differences were noted in multiple demographics including education, smoking, hypertension, cognitive and depression scores, and sleep assessment scores. Anti-parkinsonian medication was temporarily withheld prior to the MRI where relevant, though the effect of this on results is unclear. The Hoehn and Yahr scale identified a mean score of 2.34 within the PD cohort suggesting the exclusion of those with more advanced disease.

The ALPS index was lowest in individuals with PD, followed by RBD, and healthy controls respectively. ALPS scores also correlated with disease severity within the PD and RBD groups. A follow-up group of 50 patients with established PD did not show any significant difference in ALPS from their baseline scan, suggesting it may have limited value as a modality for monitoring disease progression, although the timeframe of expected change will require further investigation.

Comment: The novel application of this emerging technology, together with issues in cohort matching, limits applicability. However, results suggest that glymphatic system dysfunction is prominent in PD and RBD versus healthy controls and is detectable via DTI. Sleep disruption in PD may be one mechanism contributing to glymphatic dysfunction with sleep thought to enhance glymphatic activity. This aberrant process may result in alpha-synuclein accumulation and have relevance for disease progression.

Si X. et al. (2022), npj Parkinson's Disease, 8(1) 1–9. https://doi.org/10.1038/s41531-022-00316-9