Progression in prediagnostic Huntington disease.
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 < or = 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.
Rupp
Jason
J
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202-5251, USA.
Blekher
Tanya
T
Jackson
Jacqueline
J
Beristain
Xabier
X
Marshall
Jeanine
J
Hui
Siu
S
Wojcieszek
Joanne
J
Foroud
Tatiana
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000503:physiopathology; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology; D018450:Disease Progression; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009483:Neuropsychological Tests; D009687:Nuclear Proteins / Q000235:genetics; D011596:Psychomotor Disorders / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D012438:Saccades; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D055815:Young Adult
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins