Practice Effects and Stability of Neuropsychological and UHDRS Tests over Short Retest Intervals in Huntington Disease

Background: In Huntington disease (HD), cognitive changes due to disease-progression or treatment are potentially confounded by "practice effects" (PE) - performance improvement from prior exposure to test materials. Objective: A practice run-in ("dual baseline") was used in an HD cognitive trial to determine if PE could be minimized and evaluate performance trajectories over multiple visits. Methods: Non-depressed adults (N= 36) with mild to moderate HD-related cognitive deficits participated in a clinical trial to examine the efficacy of citalopram to enhance cognition. Cognitive tests were administered at three visits (2 weeks separating each visit), before active treatment randomization. Some tests were also administered at screening. Therefore 3-4 pre-treatment repetitions were available. We examined test improvement using repeated-measures ANOVAs with planned pairwise comparisons. Results: Despite the practice run-in and use of alternate test forms, results indicated ongoing improvements over at least three test sessions on all three UHDRS cognitive tests. Trails A and B showed improvements between the third and fourth session, which suggests that one pre-baseline visit may not be effective in reducing practice on this important and commonly used test. Conclusions: Overall, 7 out of 13 variables showed some degree of short-term PE, even after multiple sessions and alternate forms. Tests assessing processing speed and memory may be particularly confounded by ongoing PE across at least 2-3 sessions. Practice run-in periods and alternate forms may help minimize the impact of such effects in HD clinical trials but awareness of which tests are most susceptible to PE is important in clinical trial design.