Relationships between neuroimaging biomarkers and glymphatic-system activity in dementia with Lewy bodies

Alpha-synuclein deposits in the brain have been suspected to cause Parkinson’s disease and dementia with Lewy bodies (DLB). It was recently revealed that the glymphatic system is largely responsible for the removal of alpha-synuclein. We investigated changes in the glymphatic system’s activity by determining the DTI‑ALPS (diffusion tensor image analysis along the perivascular space) index in DLB patients. Twenty-six patients with DLB and 43 healthy subjects underwent diffusion tensor imaging (DTI) scanning at our hospital during the period April 2013 to March 2023. We retrospectively computed each subject’s DTI‑ALPS index to evaluate his/her glymphatic-system activity and then analyzed the relationships between the subjects’ DTI‑ALPS index data and their DLB neuroimaging biomarker values. A significant reduction of the DTI‑ALPS index was observed in the patients with DLB compared to the healthy subjects. Significant positive correlations were also detected in the DLB group between the DTI‑ALPS index and the regional gray matter volume in the left insula and between the index and the specific binding ratio of ¹²³I–N-ω-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)nortropane ([¹²³I]-FP-CIT). These results indicate that (i) the DTI‑ALPS index is a good biomarker of the progression of DLB, and (ii) this index might be effective to distinguish DLB from other neurocognitive disorders.