Prevalence, and Predictors, of Vascular Cognitive Impairment in CADASIL

Abstract

Abstract Background and Objective CADASIL is the most common monogenic form of stroke and early onset dementia. We determined the prevalence of vascular cognitive impairment (VCI) in a cohort of CADASIL patients, and investigated which factors were associated with VCI risk, including clinical, genetic and MRI parameters. Methods Cognition was assessed in genetically confirmed CADASIL patients (n = 176) and healthy controls (n= 265) (mean(SD) age 50.95(11.35) v 52.37(7.93) years), using the Brief Memory and Executive Test (BMET) and the Montreal Cognitive Assessment (MoCA). VCI was defined according to previously validated cut-offs. We determined the prevalence of VCI and its associations with clinical risk factors, mutation location (EGFr 1-6 versus EGFr 7-34), and MRI markers of small vessel disease. Results VCI was more common in CADASIL than controls; 39.8 v 10.2% on BMET 47.7% v 19.6% of MOCA. CADASIL patients had worse performance across all cognitive domains. History of stroke was associated with VCI on the BMET (OR 2.12, 95% CI [1.05, 4.27] p = 0.04) and on the MoCA (OR 2.55 [1.21, 5.41] p = 0.01), after controlling for age and sex. There was no association of VCI with mutation site. Lacune count was the only MRI parameter independently associated with VCI on the BMET (OR: 1.63, 95% CI [1.10, 2.41], p = 0.014), after controlling for other MRI parameters. These associations persisted after controlling for education in the sensitivity analyses. Conclusions VCI is present in almost half of CADASIL patients with a mean age of 50. Stroke and lacune count on MRI were both independent predictors of VCI on the BMET.