The pattern of cognitive performance in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Background and purpose: small vessel disease (SVD) is a major cause of vascular dementia. CADASIL is a monogenic variant of SVD caused by mutations in NOTCH3. Mutation carriers almost invariably develop cognitive deficits. The current study determines the characteristics of cognitive abnormalities seen in CADASIL. Methods: 65 mutation carriers and 30 matched control subjects underwent a series of assessments including global cognitive scores (Mattis Dementia Rating Scale, MDRS; Mini-Mental State Examination, MMSE) the VaDAS-cog battery as well as specific tests for executive function and attention with measures of processing speed and error monitoring. Subgroups were defined according to MDRS scores. Results: CADASIL subjects had pronounced deficits in attention and executive performance with particular impairments of timed measures (Stroop II and III, Trail Making) and the number of correct responses (symbol digit and digit cancellation tasks) (all p<0.002). Measures of error monitoring (Stroop III, Trail Making, Symbol digit, Maze) were also affected but to a lesser extent (all p<0.05). Further deficits were present on verbal fluency and ideational praxis. Recall, orientation, and receptive language skills were largely unaffected. Subgroup analyses indicated a similar profile in subjects with mild impairment of global cognitive performance (MDRS score>123) compared to those with marked deficits (MDRS score <122). Conclusions: our findings highlight processing speed as the most substantial area of cognitive impairment in CADASIL, with less pronounced yet significant deficits of other aspects of executive performance and attention. This profile of cognitive impairment is present already at an early stage of the disease and enables the construction of targeted test batteries for clinical trials.