Asymptomatic Cerebral Small Vessel Disease: Insights from Population-Based Studies

Abstract

Cerebral small vessel disease (CSVD) is a common group of neurological conditions that confer a significant burden of morbidity and mortality worldwide. In most cases, CSVD is only recognized in its advanced stages once its symptomatic sequelae develop. However, its significance in asymptomatic healthy populations remains poorly defined. In population-based studies of presumed healthy elderly individuals, CSVD neuroimaging markers including white matter hyperintensities, lacunes, cerebral microbleeds, enlarged perivascular spaces, cortical superficial siderosis, and cerebral microinfarcts are frequently detected. While the presence of these imaging markers may reflect unique mechanisms at play, there are likely shared pathways underlying CSVD. Herein, we aim to assess the etiology and significance of these individual biomarkers by focusing in asymptomatic populations at an epidemiological level. By primarily examining population-based studies, we explore the risk factors that are involved in the formation and progression of these biomarkers. Through a critical semi-systematic review, we aim to characterize "asymptomatic" CSVD, review screening modalities, and draw associations from observational studies in clinical populations. Lastly, we highlight areas of research (including therapeutic approaches) in which further investigation is needed to better understand asymptomatic CSVD.

Keywords: Cerebral small vessel diseases; Epidemiology; Leukoaraiosis; Stroke, lacunar.

Figure 1.

Imaging features of cerebral small vessel disease biomarkers on magnetic resonance imaging. (A) T2 fluid attenuated inversion recovery (FLAIR) sequence depicting white matter hyperintensities (red arrowhead) which are seen as hyperintense regions in the white matter. (B) Lacune (red arrowhead) on FLAIR sequence characterized by a central hypointensity with a surrounding rim of hyperintensity. (C) Recent subcortical infarct (red arrowhead) on diffusion-weighted imaging sequence between 3 to 15 mm in diameter. (D) Susceptibility-weighted imaging (SWI) sequence showing cerebral microbleeds (red arrowhead) which are round/oval shaped signal voids ≤10 mm and have associated blooming artifact. (E) Perivascular spaces (red arrowhead) on T2 which are linear cavitations that do not have a surrounding rim of hyperintensity and are <3 mm in diameter. (F) Cortical superficial siderosis (red arrowhead) visualized on SWI and characterized by a curvilinear hypointensity that follows the gyral surface. (G) Cerebral microinfarct (<5 mm in diameter) is hyperintense on T2 FLAIR (see inset, red arrowhead) and (H) hypointense on T1 (see inset, red arrowhead). Images (G) and (H) were graciously provided by Susanne Van Veluw.