The relationship between CAG repeat length and clinical progression in Huntington's disease

Abstract

The objective of this study was to examine the relationship between CAG repeat length (CAGn) and clinical progression in patients with Huntington's disease (HD). There are conflicting reports about the relationship between CAGn and clinical progression of HD. We conducted an analysis of data from the Coenzyme Q10 and Remacemide Evaluation in Huntington's Disease (CARE-HD) clinical trial. We modeled progression over 30 months on the Unified Huntington's Disease Rating Scale (UHDRS) and supplemental neuropsychological and behavioral tests using multiple linear regression. Mean subject age was 47.9 +/- 10.5 years and mean CAGn was 45.0 +/- 4.1. Multiple linear regression revealed statistically significant associations between CAGn and worsening on several motor, cognitive, and functional outcomes, but not behavioral outcomes. Many effects were clinically important; 10 additional CAG repeats were associated with an 81% increase in progression on the Independence Scale. These associations were not observed in the absence of age adjustment. Age at the time of assessment confounds the association between CAGn and progression. Adjusting for age shows that longer CAGn is associated with greater clinical progression of HD. This finding may account for the variable results from previous studies examining CAGn and progression. Adjusting for CAGn may be important for clinical trials.