Isometric force matching in the TRACK-HD study - a novel quantitative assessment for clinical applications?

Abstract

BackgroundHuntington's disease is a rare, progressive, neurodegenerative disease. Capturing symptomatic progression and treatment effects reliably in clinical therapeutic trials has shown to be a challenging task, facing the problem of small cohorts and a variable phenotype. Hence, robust and sensitive outcome measures are needed, to assess efficacy and safety of novel therapies in clinical studies with small cohorts.ObjectiveObjectives of this study were to assess feasibility, discriminative potential, and correlation to clinical and imaging endpoints of the Q-Motor isometric force matching task with visual feedback. Furthermore, a statistical comparison with the Q-Motor grasping and lifting task should be assessed.Methods220 huntingtin gene expansion carriers (HGEC) and 110 non-huntingtin gene expansion carrier (Non-HGEC) participants of the observational TRACK-HD study completed the Q-Motor force matching assessment, along with a standard battery of clinical tests (UHDRS) and MRI assessments. During the Q-Motor force matching assessments, patients were reproducing a target force in precision grip with help of visual feedback. Q-Motor utilizes a highly sensitive force transducer to record force feedback. HGEC participants were categorized into four groups by a CAG- and age-based survival score.ResultsQ-Motor force matching allowed for very good discrimination between HGEC and Non-HGEC participant groups (p < 0.001 for all but least affected HGEC group) and between different HGEC groups (all p < 0.05). Strong correlations with UHDRS scores (TMS = -0.708, TFC = -0.638), CAG-Age product scores (Survival Score = 0.626) and imaging outcomes (caudate volume = -0.609, striatum volume = -0.624) were observed. A statistical difference between correlation strength of Q-Motor force matching and Q-Motor grasping and lifting tasks could not be observed.ConclusionsCross-sectional analysis of Q-Motor force matching showed promising results, outperforming clinical rating scales in sensitivity. Further efforts are required to assess longitudinal robustness of the task, and to further explore its potential of capturing cognitive effects by increasing cognitive load during the task.