Central Cognitive Processing Speed Is an Early Marker of Huntington's Disease Onset

Abstract

Background Background: Several studies have suggested that cognitive processing speed may be useful for assessing early cognitive change in premanifest Huntington's disease (HD); however, current measures lack the ability to control for the effects of motor dysfunction commonly found in HD. The Computerized Test of Information Processing (CTiP) is a rapidly administered computerized tool that allows for the examination of central cognitive processing speed by using motor-corrected scores to account for motor dysfunction. Objective Objective: To examine central cognitive processing speed as an early marker of HD onset using the CTiP. Methods Methods: The CTiP and other measures were administered to 102 HD gene carriers and 55 healthy adults (HA). Gene carriers included presymptomatic HD (pre-HD; n = 33), prodromal HD (pro-HD; ie, individuals close to disease onset; n = 23), and mild-moderate HD (HD; n = 46). Results Results: The HD group performed significantly slower than all other groups (HA, pre-HD, and pro-HD) on most subtests (Ps < .05). Moreover, the pro-HD group performed significantly slower than the HA group on both motor-corrected subtests (Ps < 0.05). Effect sizes associated with significant group differences between the pro-HD and HA groups on motor-corrected CTiP subtests (d = 0.73 and 0.84) were similar to effect sizes associated with group differences on the Symbol Digit Modalities Test (d = .82) and other traditional cognitive assessments (Montreal Cognitive Assessment, d = .75; Mini-Mental State Examination, d = .84). Conclusions Conclusions: The CTiP may be a useful marker of deficits in central cognitive processing speed in individuals close to manifest onset of HD.

Exploring bradyphrenia in Huntington’s disease using the computerized test of information processing (CTiP)

“…Finally, we note that impairments in executive functioning or semantic verbal skills may contribute to the quantification of bradyphrenia in our study. Our previous analysis of cognitive processing in HD, as measured by the CTiP, displayed greater reaction times for the CRT compared to the SRT, suggesting that this increase is not purely due to differences in semantic verbal skills [9] ; however, further research into bradyphrenia would benefit from the inclusion of additional levels of cognitive difficulty.…”

“…We have previously shown that deficits in central cognitive processing, as measured by the CTiP CRT-SRT and SSRT-SRT measures, become apparent during the prodromal and manifest HD stages [9] . The present study builds on these findings, by showing that the within-group reaction time differences between choice (CRT-SRT) and semantic search (SSRT-SRT) responses, corrected for motor performance, increase with HD disease stage.…”

“…Moreover, the capability to correctly respond to questions, as measured by the MoCA, is different from the time taken to process a response. While the SDMT does assess both the extent to which an individual can complete the test, as well as the speed (or completion rate) at which this is done, the CTiP is once again advantageous as it includes a measure of SRT, which may then be subtracted from the more cognitively taxing CTiP tasks in order to obtain motor-corrected, central cognitive conduction times [9] . Conversely, the SDMT, and visuospatial/executive measures of the MoCA, may be impacted by elements of both bradykinesia and akinesia.…”

“…The CTiP was performed as previously described, using CTIP 5.0 (Build 2, via Multi-Health Systems, ON, CA) [9] , [17] , [18] . Briefly, the participant completed three computerized response time (RT) subtests, each consisting of 30 trials preceded by 10 practice trials.…”

“…The lack of rigorous investigation of bradyphrenia in HD is surprising, as HD was one of the first disorders within which the concept of subcortical dementia – characterized in part by a slowness of mental processing – was first recognized [7] , [8] . In addition, we have recently shown that cognitive processing deficits appear to arise during the prodromal and manifest stages of HD, as quantified using the Computerized Test of Information Processing (CTiP) [9] . Notably, while the CTiP has been used to measure cognitive processing in studies of traumatic brain injury [10] and, predominantly, multiple sclerosis [11] , [12] , [13] , [14] , [15] , to our knowledge we are the first to utilize this measure in the field of HD research.…”