Neuropsychological performance and disease burden in individuals at risk of developing Huntington disease

Introduction

Huntington disease (HD) is a hereditary neurodegenerative disorder. Thanks to predictive diagnosis, incipient clinical characteristics have been described in the prodromal phase.

Objective

To compare performance in cognitive tasks of carriers (HDC) and non-carriers (non-HDC) of the huntingtin gene and to analyse the variability in performance as a function of disease burden and proximity to the manifest stage (age of symptom onset).

Method

A sample of 146 participants in a predictive diagnosis of HD programme were divided into the HDC (41.1%) and non-HDC groups (58.9%). Mathematical formulae were used to calculate disease burden and proximity to the manifest stage in the HDC group; these parameters were correlated with neuropsychological performance.

Results

Significant differences were observed between groups in performance on the Mini–Mental State Examination (MMSE), Stroop-B, Symbol-Digit Modalities Test (SDMT), and phonological fluency. In the HDC group, correlations were observed between disease burden and performance on the MMSE, Stroop-B, and SDMT. The group of patients close to the manifest stage scored lowest on the MMSE, Stroop-B, Stroop-C, SDMT, and semantic verbal fluency. According to the multivariate analysis of covariance, the MMSE effect shows statistically significant differences in disease burden and proximity to onset of symptoms.

Conclusions

Members of the HDC group close to the manifest phase performed more poorly on tests assessing information processing speed and attention. Prefrontal cognitive dysfunction appears early, several years before the motor diagnosis of HD.