Measurement of meaningful treatment effects in CADASIL

Abstract

I read with interest Martin Dichgans and colleagues' study of donepezil in CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy), in the April issue of The Lancet Neurology. 1 Dichgans M Markus HS Salloway S et al. Donepezil in patients with subcortical vascular cognitive impairment: a randomized double-blind trial in CADASIL. Lancet Neurol. 2008; 7: 310-318 Summary Full Text Full Text PDF PubMed Scopus (191) Google Scholar The researchers found significant effects on two measures of executive control function, including the executive interview (EXIT25). 2 Royall DR Mahurin RK Gray K Bedside assessment of executive cognitive impairment: the executive interview (EXIT). J Am Geriatr Soc. 1992; 40: 1221-1226 PubMed Google Scholar The EXIT25 effect of −1·5 points out of 50 was comparable to that in an earlier study by Auchus and co-workers 3 Auchus AP, Brashear HR, Salloway S, et al. Results of a trial of galantamine in subjects with vascular dementia confirmed by central MRI reading. American Academy of Neurology Meeting, San Francisco, CA, USA. April 27, 2004. Google Scholar of galantamine in patients with vascular dementia as defined by the National Institute of Neurological Disorders and Stroke (NINDS). Measurement of meaningful treatment effects in CADASIL – Authors' replyWe appreciate Dr Royall's comments on the EXIT25. We agree that the beneficial effect of donepezil on the EXIT25 scores, albeit statistically significant, might not be clinically meaningful. In fact, the lack of treatment effects on instrumental activities of daily living and global dementia rating, as assessed by the disability assessment for dementia and the sum of boxes of the clinical dementia rating scale seems to support this view. We also agree that, on average, patients in the current trial were mildly affected and that this might have limited our ability to detect clinically meaningful improvements in both executive function and instrumental activities of daily living. Full-Text PDF