Genotype - phenotype correlation in CADASIL. Cognitive performance in carriers of notch3 mutations R1031C and C455R

Abstract

Even though cognitive impairment in brain vascular disease has been widely described, there is not much known about specific neuropsychological profiles in affected families suffering from hereditary vascular dementia CADASIL. In Colombia we have reported for the first time two large kindreds suffering from CADASIL in the Antioquia region (Colombia). Those families carry mutations R1031C and C455R in notch 3 gene, respectively. In this study, we have develop a comparative analysis between 16 affected carriers of R1031C (family A) and 7 affected carriers of mutation C455R (family B). This includes a description of cognitive performance in these two groups applying specific protocols evaluating several cognitive functions, depression and everyday functionality. Analysis showed differences in age of onset, evolution time, dementia diagnosis and degree of leukoencephalopaty between R1031C and C455R carriers. Statistically significant differences were found in tests evaluating multiple cognitive domains with higher prevalence of cognitive impairment and dementia in R1031C carriers (p<0.05). There were not statistically significant differences in tests evaluating sustained attention, abstract reasoning, semantical and phonological fluence, reading, arithmetic, executive functions, depression scales and functional scales.

Keywords

• Hereditary vascular dementia
• leukoencephalopathy
• cognitive performance in CADASIL
• neuropsychological markers.