Two distinct patterns of progression of sporadic cerebral small vessel disease.

BACKGROUND

Sporadic cerebral small vessel disease (cSVD) is the most common cause of vascular dementia. cSVD features a wide range of neuroimaging markers, including white matter hyperintensity (WMH), lacunes, perivascular spaces, microbleeds, and diffusion magnetic resonance imaging (MRI)-based markers of white matter (WM) injury, and is accompanied by progressive cognitive decline. However, few studies have systematically investigated how and when various imaging and cognitive markers change along the complete cSVD progression trajectory.

AIMS: To establish changes in imaging and cognitive markers along the cSVD progression trajectory.

METHODS

In this cohort study, we selected 496 participants from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUNDMC) cohort as the discovery data set. The subtype and stage inference model was used to identify cSVD subtypes and their progression patterns. Five neuroimaging markers (WMH volume, median mean diffusivity (MD) in WM, WM volume, gray matter (GM) volume, and ventricle volume) were used in trajectory construction. The validation cohort was Cambridge cSVD (CamcSVD; n = 330).

RESULTS

We identified two subtypes in RUNDMC and replicated this finding in CamcSVD. One subtype displayed early WMH increase, followed by increased WM MD and tissue volume loss. The other subtype, which we termed "atrophy predominant," showed early loss of GM and WM and ventricle enlargement, followed by WMH increase and increased WM MD. This subtype displayed an increase in markers of idiopathic normal pressure hydrocephalus (iNPH).

CONCLUSION

We have delineated two distinct progression patterns in sporadic cSVD. Further studies are needed to investigate the relationship between the atrophy-predominant cSVD subtype and iNPH.Data access statement:Datasets may be shared upon request to the corresponding author.