Neuropsychological stability over two years in asymptomatic carriers of the Huntington's disease mutation.

Abstract

This study examined whether neuropsychological changes emerge over time in asymptomatic adults who have the

Neuropsychological Deficits in Huntington's Disease Gene Carriers and Correlates of Early "Conversion"

“…15,16 While no overall group differences were identified between the mutation-positive and mutation-negative groups we described in 2002, 17 a median split of the mutation-positive group on estimated time to onset (8.1 years) yielded significant group differences. Mutation-carriers who were closer to predicted illness onset (mean=4.0 years) performed significantly worse than those further from onset (mean=13.1 years) on the Symbol Digit Modalities Test, WAIS-R Block Design subtest, and all trials of the Stroop test, as well as the Standardized Road-Map Test of Directional Sense and nondominant hand performance on the Grooved Pegboard Test.…”

“…15 These two groups of mutation carriers did not differ significantly in predicted time to onset, nor did they differ in the length of time they had been followed at the time of these analyses. Subjects in the converter group had actual onset of Huntington's disease an average of 7.94 years after their baseline visit (SD=4.89, range=1.82-18.28 years); their mean predicted time to onset was 7.12 years (SD=4.61, range=−2.57-15.06 years).…”

“…In those studies where proximity to clinical onset was explicitly addressed, time to disease onset ("conversion") was most often estimated. 10,[15][16][17]28 The present study is one of the very few reporting data from those who have been followed prospectively from asymptomatic status to diagnosable disease onset. 18,22 Other factors likely contributing to discrepant research findings include differences in the variety and sensitivity of the specific cognitive tests employed and differences in statistical power to detect group differences (due primarily to sample size).…”

“…Several investigations reported no significant differences in neuropsychological functioning between those with and those without the Huntington's disease mutation. [13][14][15][16][17] Others, however, have found such differences. [8][9][10]18 Deficits in reaction time, psychomotor and processing speed, 10,18,[20][21][22] executive functioning, [23][24][25] spatial analysis and constructional praxis, 26 verbal fluency, 23 verbal memory, [26][27][28] and mental arithmetic 9,10 have all been reported among mutation carriers, albeit inconsistently.…”

Biomarkers for Huntington’s Disease

“…Subtle cognitive changes are present already in presymptomatic gene carriers (Kirkwood et al 2001, Craufurd & Snowden 2002; they become evident close to onset and early in the course of the disease and grow to be more severe as the disease evolves (Campodonico et al 1996;Brandt & Butters 1986). Cognitive changes therefore have the potential to identify premanifest HD gene carriers close to the onset of the disease.…”