No abstract

Background: Prior studies have relied on conventional observer-based severity ratings such as the Unified Huntington’s Disease Rating Scale (UHDRS) to identify early motor markers of decline in Huntington’s disease (HD). Objective: The present study examined the predictive utility of graphomotor measures handwriting and drawing movements. Methods: Seventeen gene-positive premanifest HD subjects underwent comprehensive clinical, cognitive, motor, and graphomotor assessments at baseline and at follow-up intervals ranging from 9–36 months. Baseline graphomotor assessments were subjected to linear multiple regression procedures to identify factors associated with change on the comprehensive UHDRS index. Results: Subjects were followed for an average of 21.2 months. Three multivariate regression models based on graphomotor variables derived from a complex loop task, a maximum speed circle drawing task and a combined task returned adjusted R2 coefficients of 0.76, 0.71, and 0.80 respectively accounting for a significant portion of the variability in cUHDRS change score. The best-fit model based on the combined tasks indicated that greater decline on the cUHDRS was associated with increased pen movement dysfluency and stroke-stroke variability at baseline. Conclusion: Performance on multiple measures of graphomotor dysfluency assessed during the premanifest or prodromal stage in at-risk HD individuals was associated with decline on a multidimensional index on HD morbidity preceding an HD diagnosis.