Self-paced timing detects and tracks change in prodromal Huntington disease.
OBJECTIVE
This study compares self-paced timing performance (cross-sectionally and longitudinally) between participants with prodromal Huntington's disease (pr-HD) and a comparison group of gene non-expanded participants from affected families (NC).


METHODS
Participants (747 pr-HD: 188 NC) listened to tones presented at 550-ms 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 other demographic factors.


RESULTS
Pr-HD participants showed significantly less timing precision than NC. Comparison of pr-HD and NC participants showed a significant performance difference on two task administration conditions (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). Longitudinal modeling showed that pr-HD participants worsen more quickly at the task than the NC group, and rate of decline 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.


CONCLUSIONS
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.
Rowe
Kelly C
KC
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Paulsen
Jane S
JS
Langbehn
Douglas R
DR
Duff
Kevin
K
Beglinger
Leigh J
LJ
Wang
Chiachi
C
O'Rourke
Justin J F
JJ
Stout
Julie C
JC
Moser
David J
DJ
D000161:Acoustic Stimulation / Q000379:methods; D000328:Adult; D000368:Aged; D001288:Attention / Q000502:physiology*; D001307:Auditory Perception / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000502:physiology; D012649:Self Concept; D013998:Time Perception / Q000502:physiology*; D055815:Young Adult