Examining the Cognitive Profile of Small Vessel Disease across Stages of Severity - A Systematic Review and Meta-Analysis

Cognitive impairment is a key consequence of small vessel disease (SVD), yet prior work has often dichotomised cognitive outcomes as either intact or impaired, obscuring domain- and severity-specific effects. We conducted three-level random-effects meta-analyses to examine cognitive performance across multiple cognitive domains and levels of SVD severity. A total of 24 studies met the inclusion criteria, of which 16 provided sufficient group summary data of White Matter Hyperintensity (WMH) pathology for quantitative synthesis. The remaining studies contributed to descriptive analyses, which synthesised broader SVD pathology types. Processing speed showed the earliest and strongest deficits, with small effects at low WMH burden and medium-to-large effects by high WHM burden, Fazekas 3 (Fazekas 3 pooled g = − 1.02, 95% CI [− 1.46, − 0.58]). Executive function deficits emerged at moderate-to-severe stages and were large by Fazekas 3 (Fazekas 3 g = − 1.11, 95% CI [− 1.53, − 0.69]); attention/working memory estimates trended in the expected direction but did not reach significant effects at any Fazekas level, reflecting the small number of contributing studies. In contrast to processing speed and executive function, verbal and visual memory showed small effects at low burden that reached large by Fazekas 3, while confrontation naming effects remained small-to-medium across severity levels and general intelligence did not differ significantly from controls at any level. Between- and within-study variance components indicated substantial residual heterogeneity across several cognitive domains. Together, the meta-analytic and descriptive findings provide converging evidence that reduced processing speed is an early marker of SVD-related cognitive change, with broader deficits emerging at greater severity. Collectively, these findings provide further insights into the cognitive profile of SVD and underscore the need for additional research, particularly across SVD pathologies beyond WMH.