Proximity to Clinical Onset Influences Motor and Cognitive Performance in Presymptomatic Huntington Disease Gene Carriers

Movement sequencing in Huntington disease

“…This suggests a progressive impairment in the execution of sequential motor programs, and a greater reliance upon the ongoing deliberate control of movement, manifest during the “in-flight” or execution phase when a switch is required between motor segments (reflecting movement time). This may also explain why this and many previous studies have reported impaired movement times, rather than initiation times, in symptomatic HD (Hefter et al 1987; Girotti et al 1988; Agostino et al 1992; Bradshaw et al 1992; Georgiou et al 1995; Farrow et al 2006; Yágüez et al 2006). This pattern of deficit may represent an early dysfunction in the motor circuit in the high CAP group as they approach diagnosis with respect to phasic activity that may impair the cue necessary to start the pre-movement activity for the next switch movement in the sequence (Tanji and Kurata 1985; Brotchie et al 1991; Boecker et al 1998; Elsinger et al 2006; Lehéricy et al 2006).…”

“…Bradshaw et al (1992) showed that “at-risk” individuals, especially those already diagnosed with HD, demonstrated increased movement times with low advance information (condition 1). Farrow et al (2006) also demonstrated that probability of 5-year diagnosis was associated with increased movement times only for conditions 1 and 2. We showed that although the high CAP group demonstrated the strongest effect for slopes, this effect was consistent across all three conditions, whereas in contrast, error levels remained relatively stable across follow-up sessions.…”

“…Cross-sectional motor studies in late prodromal Huntington disease (HD) report various motor deficits, including abnormal muscle stretch reflexes, diminished rapid alternating movements, increased movement jerkiness, diminished motor timing, and impaired sequence learning (Kirkwood et al 2000; Smith et al 2000; Snowden et al 2002; Farrow et al 2006; Feigin et al 2006; Andrich et al 2007; Hinton et al 2007; Doyon 2008; Ghilardi et al 2008). Longitudinal changes in motor functioning over 2–10 years prior to onset include decline in repetitive alternating movements, psychomotor speed, motor timing, saccades and paced and self-paced finger tapping (Penney et al 1990; Giordani et al 1995; Campodonico et al 1996; Kirkwood et al 1999; Lemiere et al 2002, 2004; Witjes-Ane et al 2007; Solomon et al 2008; Antoniades et al 2010; Rowe et al 2010; Maroof et al 2011).…”

“…The Bradshaw et al study was the first to suggest that cued movement sequencing could be a sensitive indicator of programming deficits in prodromal HD. Further research found that probability of diagnosis within 5 years was associated with increased mean movement times for both low and moderate levels of advance information (Farrow et al 2006), suggesting likely cognitive-motor deficits as individuals approach diagnosis. The PREDICT-HD study provides the first opportunity to examine longitudinal changes in programming and online control of motor sequences in a large prodromal HD sample stratified into baseline progression groups.…”

Are Cognitive Changes Progressive in Prediagnostic HD?

“…[10][11][12][13][14] The results of prediagnosis studies are less consistent. [15][16][17][18][19][20] This may be due to small sample sizes that were inadequate to detect the relatively subtle changes that occur in the prediagnosis phase. Also, individuals with the CAG expansion who are far from diagnosis may be functioning normally, and may not show significant declines in function until they approach the point of diagnosis.…”