This study compares self-paced timing performance (cross-sectionally and longitudinally) between participants with prodromal Huntington disease (pr-HD) and a comparison group of gene non-expanded participants from affected families (NC).
At baseline, participants in two groups (747 pr-HD: 188 NC) listened to tones presented at 550ms intervals, matched that pace by tapping response keys and continued the rhythm (self-paced) after the tone had stopped. Standardized cross-sectional and longitudinal linear models examined the relationships between self-paced timing precision and estimated proximity to diagnosis, and various other demographic factors.
Pr-HD participants showed significantly less timing precision than NC. Cross-sectional comparison of pr-HD and NC participants showed a significant performance difference on two administration conditions of the task (dominant hand: p<.0001; alternating thumbs: p<.0001). Additionally, estimated proximity to diagnosis was related to timing precision in both conditions, (dominant hand: t=−11.14,df=920, p<.0001; alternating thumbs: t=−11.32, df=918, p<.0001), even considering demographic and experience variables. Longitudinal modeling showed that pr-HD participants worsen more quickly at the task than the NC group, and that decline rate increases with estimated proximity to diagnosis in both conditions (dominant hand: t=−2.85,df=417, p=.0045; alternating thumbs: t=−3.56, df= 445, p=.0004). Effect sizes based on adjusted mean annual change ranged from −0.34 to 0.25 in the longitudinal model.
The self-paced timing paradigm has potential for use as a screening tool and outcome measure in pr-HD clinical trials to gauge therapeutically-mediated improvement or maintenance of function.