This study aimed to investigate the relationship of NOTCH3 variant positions, the causal genetic variant of CADASIL, with executive dysfunction measured at baseline as well as two years later at...Show moreThis study aimed to investigate the relationship of NOTCH3 variant positions, the causal genetic variant of CADASIL, with executive dysfunction measured at baseline as well as two years later at follow-up. This was done by comparing NOTCH3 variant positions in groups (risk categories) associated with a high (N = 104) or moderate (N = 76) risk of developing worse disease outcomes. It was expected that the high risk group would perform significantly worse and decline significantly more than the moderate risk group on neuropsychological tests measuring executive functioning. Executive dysfunction was assessed using the following neuropsychological tests: Trail Making Test, Stroop Color and Word Test, WAIS-R Digit Symbol Substitution Test and WAIS-IV Block Design Test. A Linear Mixed Model (Repeated Measurements) analysis was performed to answer the objectives with a total of 180 included participants. There was no significant difference in performance between the risk categories at baseline, nor in the decline in performance over the two-year follow-up span. In an exploratory follow-up analysis, we examined whether decline was present at all, regardless of risk category. This was only the case for one of four neuropsychological tests. In conclusion, future clinical trials are needed to provide better understanding of how NOTCH3 aggregation impacts executive dysfunction and its development thereof within CADASIL. Subsequently, this could allow for more accurate individualised disease progression predictions.Show less
