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 MRI-based markers of white matter injury, and is accompanied with 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 of imaging and cognitive markers along the cSVD progression trajectory. METHODS: In this cohort study, we selected 496 participants from the RUNDMC cohort as the discovery dataset. 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 white matter, white matter volume, gray matter volume and ventricle volume) were used in trajectory construction. The validation cohort was 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 white matter MD and tissue volume loss. The other subtype, which we termed "atrophy predominant", showed early loss of gray and white matters and ventricle enlargement, followed by WMH increase and increased white matter MD. This subtype displayed an increase in markers of idiopathic normal pressure hydrocephalus (iNPH). CONCLUSIONS: 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 requests to the corresponding author.