The cognitive profiles of CADASIL and sporadic small vessel disease

Background: Interpretation of treatment trials in vascular dementia is confounded by the presence of coexistent Alzheimer disease (AD) pathology. The younger onset genetic disease cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) offers a model of pure vascular dementia, in which such confounding is unlikely. To validate CADASIL's use as a model it is important to show it results in a similar cognitive impairment. Methods: The same neuropsychological assessment was administered to patients with CADASIL (n = 34, 14 of whom had had stroke), sporadic small vessel disease (SVD) presenting with lacunar stroke and having confluent leukoaraiosis (n = 54), and healthy controls (n = 25). Results: A similar pattern of neuropsychological impairment was seen in the two diseases, with prominent early executive dysfunction. Patients with CADASIL and SVD performed worse than controls on Trails switching test (CADASIL p = 0.006; SVD p < 0.001), and on verbal fluency test (CADASIL p = 0.015; SVD p = 0.004). The SVD group also performed worse on immediate ( p = 0.050) and delayed (p = 0.049) memory. When only patients with CADASIL with stroke were included in analysis with SVD subjects, all of whom had had stroke, a very similar cognitive profile was seen. The only difference was on verbal fluency, where CADASIL subjects performed worse (p = 0.044). Conclusion: Patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and small vessel disease show a similar pattern of cognitive deficits. This suggests that CADASIL provides a model of pure vascular dementia relevant for sporadic small vessel disease vascular dementia.