Viswanathan A et al. (2007) Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL. Neurology 69: 172–179

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutation of the NOTCH3 gene and is considered a model of 'pure' vascular dementia. MRI scans from patients with CADASIL show white matter hyperintensities, lacunar lesions and cerebral microhemorrhages, but the clinical importance of these lesions is unclear. By collecting data from 147 consecutive patients enrolled in a two-center prospective cohort trial, Viswanathan and co-workers assessed the relationship of these MRI markers with cognitive impairment and disability in CADASIL.

Multivariate analysis demonstrated that cognitive function, as assessed by either the Mattis Dementia Rating Scale or the Mini-Mental State Examination, was independently associated with age and volume of lacunar lesions only. Neither white matter hyperintensities nor cerebral microhemorrhages were found to be independently associated with cognitive function. Stepwise logistic regression was also performed to determine independent predictors of functional disability in CADASIL. The maximally adjusted model revealed increased volume of lacunar lesions, number of cerebral microhemorrhages and age, as well as high systolic blood pressure, to be independent predictors of a poor functional outcome as assessed by the modified Rankin scale. A similar analysis using the Barthel index to assess disability revealed increased volume of lacunar lesions, increased age and presence of cerebral microhemorrhages to be independent predictors of a poor outcome.

The authors conclude that among the lesions visible on conventional MRI, overall lacunar lesion burden is the most important predictor of cognitive impairment and disability in patients with CADASIL.