Clinical and brain volumetric correlates of decreased DTI-ALPS, suggestive of local glymphatic dysfunction, in iRBD

Abstract

Glymphatic alterations may underlie neurodegeneration in alpha-synucleinopathies. Reduced Diffusion-Tensor Imaging ALong the Perivascular Space (DTI-ALPS), a proxy of perivascular glymphatic activity, has been scarcely studied in isolated REM sleep behaviour disorder (iRBD), a prodromal synucleinopathy stage. Furthermore, its associations with clinical symptoms and brain structural abnormalities remain unexplored. We assessed the DTI-ALPS in sixty-two patients with iRBD and twenty-three healthy controls (HC), exploring its associations with clinical symptoms, cortical thickness and brain volumetric data. iRBD patients exhibited a lower DTI-ALPS and poorer odor identification, semantic fluency and processing speed relative to HC. The DTI-ALPS positively correlated with cognitive performance, olfactory function and amygdalar, hippocampal, brainstem and diencephalic volumes, and negatively with age in iRBD. Perivascular glymphatic activity is compromised in iRBD and is associated with brain atrophy and clinical risk factors of progression to alpha-synucleinopathies, supporting the potential of the DTI-ALPS index as an early imaging neurodegeneration marker.

Fig. 1. Group comparisons in bilateral DTI-ALPS index and correlations with clinical variables.

Left Group differences in bilateral DTI-ALPS index. Right Significant correlations between bilateral DTI-ALPS index and age, UPSIT-40 scores, SDMT and semantic fluency. Data corresponding to iRBD are presented in red, whereas data for HC are presented in blue. Abbreviations: DTI-ALPS, diffusion tensor imaging along the perivascular space; HC, healthy controls; iRBD, isolated Rapid-Eye-Movement disorder; r, correlation coefficient of the iRBD group; SDMT, Symbol-Digit Modality Test- oral version; p, p-value for correlations in the iRBD group; UPSIT-40, University of Pennsylvania Smell Identification Test, 40 items. Graphs were obtained using the package ggplot2 (Wickham, 2016).

Fig. 2. Associations between the DTI-ALPS index and volumetric data.

Correlation plots showing the relationship between the residuals of the DTI-ALPS and volumetric data after adjusting for age in the regression model. Data corresponding to iRBD are presented in red, whereas data for HC are presented in blue. DTI-ALPS diffusion tensor imaging along the perivascular space; B, correlation coefficient for the iRBD group; p, p-value for the correlations of the iRBD group. Graphs were obtained using the package ggplot2 (Wickham, 2016).

Fig. 3. Method for DTI-ALPS calculation.

ANTS Advanced Normalization Tools, DTI-ALPS diffusion tensor imaging aLong the perivascular space, FA fractional anisotropy, MNI Montreal Neurological Institute template.