Progression in prediagnostic Huntington disease

Abstract

Objective To examine rates of decline in individuals at risk for Huntington disease (HD). Methods 106 individuals at risk for HD completed a battery of neurocognitive, psychomotor and oculomotor tasks at two visits, approximately 2.5 years apart. Participants were classified as: (1) without the CAG expansion (normal controls, NC; n=68) or (2) with the CAG expansion (CAG+; n=38). The CAG+ group was further subdivided into those near to (near; n=19) or far from (far; n=19) their estimated age of onset. Longitudinal performance in the CAG+ group was evaluated with a repeated measures model with two main effects (time to onset, visit) and their interaction. Analysis of covariance was employed to detect differences in longitudinal performance in the three groups (NC, near and far). Results In the CAG+, the interaction term was significant (p≤0.02) for four measures (movement time, alternate button tapping, variability of latency for a memory guided task and percentage of errors for a more complex memory guided task), suggesting the rate of decline was more rapid as subjects approached onset. Longitudinal progression in the three groups differed for several variables (p<0.05). In most, the near group had significantly faster progression than NC; however, comparisons of the NC and far groups were less consistent. Conclusions Different patterns of progression were observed during the prediagnostic period. For some measures, CAG+ subjects closer to estimated onset showed a more rapid decline while for other measures the CAG+ group had a constant rate of decline throughout the prediagnostic period that was more rapid than in NC.

Huntington’s disease: changes in saccades and hand-tapping over 3 years

“…This approach can distinguish premanifest individuals from controls by virtue of the former having an increased number of early saccades (responses with unusually short latencies) [2]. Such findings are consistent with other oculomotor studies that have demonstrated the utility of saccadic latency measurement in detecting early changes in HD [1,3,10,11,33].…”

“…Hand-tapping parameters differ between HD and control populations and show high reproducibly and correlate with motor Unified Huntington's disease rating scale (UHDRS) changes over time in manifest cases of the disease [28]. However, how hand-tapping rate changes over time in premanifest patients [3,34] is currently unknown, as is whether it can be used to define the transition to manifest disease, as Saft, et al [30] have suggested.…”

Cognitive decline in prodromal Huntington Disease: implications for clinical trials

“…Six of the studies reviewed (see table 1) showed significant changes over time using the Stroop Color Word Test8 10 14–16; the TMT,14–16 or other measures of reaction or movement time,13 14 all of which were found to have substantial effects in the current study. Some have interpreted this finding as reason to emphasise motor and psychomotor measures of HD as superior to other potential assessed outcomes 12.…”

Brain Structure in Preclinical Huntington's Disease: A Multi-Method Approach

“…To this end, we employed three well-established automated methods to analyze structural data obtained from healthy controls and far-from-onset preHD: (1) the VBM Diffeomorphic Anatomic Registration Through Exponentiated Lie Algebra algorithm (DARTEL); (2) the Oxford Centre for Functional MRI of the Brain's (FMRIB's) Integrated Registration and Segmentation Tool (FIRST), and (3) the FreeSurfer software package. We went on to examine the relationship between subcortical and cortical volume with genetic and clinical variables, such as CAG repeat length and the estimated time to motor onset considering the increasing subclinical and neurobiological changes which occur with closer proximity to the motor onset of the disease [5,9,11,17,18]. We finally administered a complementary neuropsychological test battery to relate structural changes to cognitive performance.…”