Background: Cognitive impairment is a key clinical feature of cerebral small vessel disease (SVD), but the full range of SVD-related cognitive impairments is unclear, and little is known about how they might vary across clinical and non-clinical manifestations of SVD.
Methods: In systematic searches of OVID MEDLINE, Embase, and PsychINFO from 1st January 1985 to 6th October 2019, we identified studies reporting cognitive test results for study participants with SVD and control participants without SVD. Using standardised group-level cognitive test data, we performed random effects meta-analyses in seven cognitive domains to test whether cognitive test scores differed between SVD and control groups. We conducted meta-regression analyses to test whether differences in age, education, or vascular risk factors between SVD and control groups, or whether different clinical manifestations of SVD (e.g. stroke, cognitive impairment, or non-clinical presentations) accounted for cognitive effect sizes.
Findings: Of 8562 studies identified, we included 69 studies from six continents, published in four languages. These studies included 3229 participants with SVD and 3679 controls. Meta-analyses demonstrated that on average, control groups outperformed SVD cohorts on cognitive tests in all cognitive domains examined: executive function (estimate: -0.928; 95%CI: -1.08, -0.78); processing speed (-0.885; -1.17, -0.60); delayed memory (-0.898; -1.10, -0.69); language (-0.808; -1.01, -0.60); visuospatial ability (-0.720; -0.96, -0.48); reasoning (-0.634; -0.93, -0.34); and attention (-0.622; -0.94, -0.31; all p≤0.001). Meta-regression analyses suggested that differences in years of education between SVD and control groups may account for a proportion of the differences in performance on tests of executive function, visuospatial ability and language, and that cohorts with cognitive impairments performed more poorly on tests of executive function, delayed memory and visuospatial ability than cohorts with stroke or non-clinical presentations of SVD.
Interpretation: Participants with SVD demonstrated poorer cognitive performance relative to control groups in all cognitive domains we examined. This effect was present for all presentations of SVD, reinforcing the need to test a range of cognitive domains in both clinical and research settings. Lower levels of education in SVD versus control participants may contribute to these effects, highlighting the need to account for educational level in the assessment of SVD-related cognitive impairment.
