Modeling longitudinal change in motor and cognitive processing speed in presymptomatic Huntington's disease

Persons who have the genetic mutation responsible for Huntington's disease (HD) have been shown to exhibit lower cognitive test scores years prior to manifest HD. Most studies have examined cognitive performance in presymptomatic persons by using estimated times to manifest HD based on published algorithms. We followed 19 gene-positive persons who were presymptomatic using an objective criterion (i.e., Quantified Neurological Exam score <= 10) at baseline for up to 21 years (median = 5 years) with periannual neuropsychological assessments until a diagnosis of manifest HD. Results showed that our tests of information-and psychomotor-processing speed that place minimal demands on cognition, worsening performance became evident 5-10 years prior to the development of manifest HD. In conclusion, cognitive decline precedes motor signs in HD and may be an important target in clinical trials and early intervention. Cognitive test scores may also improve the ability to predict disease onset among gene mutation carriers and help families to better plan for potential personal and economic hardship.