Poster 27: Characterizing Psychomotor Declines in Prodromal Huntington Disease with the Trail Making Test

Abstract

Objective Individuals who have the Huntington disease (HD) gene-expansion but do not yet meet clinical criteria for HD (prHD) demonstrate detectable psychomotor declines long before diagnosis. The aim of this study is to assess performance on the Trail Making Test (TMT), a well known neuropsychological measure of psychomotor speed and aspects of attention and executive functioning in prHD. A secondary aim is to determine which aspects of preclinical motor decline affect TMT performance. Method A total of 984 prHD participants and non-gene expanded controls from the PREDICT-HD study were assessed with the TMT and the motor rating scale within the Unified Huntington's Disease Rating Scale (UHDRS). The TMT consists of 2 parts: TMT-A, a measure of psychomotor speed and attention, and TMT-B, which adds a cognitive set-shifting component. Index scores were seconds to complete TMT-A and TMT-B, as well as the difference between the two parts. The UHDRS motor scale was analyzed using the 5 motor factors (i.e., oculomotor, dystonia, rigidity, bradykinesia, and chorea) identified by Marder et al. (2000). PrHD participants were grouped based on estimated proximity to diagnosis (NEAR, 15 years) according to CAG repeat length and age, using Langbehn et al.'s (2004) formula. Results Linear modeling and post-hoc comparisons revealed differences between all prognostic groups, with the NEAR group performing worst on all three TMT measures (p Conclusion PrHD participants ≤15 years to diagnosis are different from controls on all TMT measures, which indicates that TMT might be a sensitive outcome measure in preventative clinical trials. Bradykinesia was most consistently associated with poorer performance, suggesting that slowed performance, rather than oculomotor changes or chorea, are most related to TMT performance.