Neuropsychological manifestations of the genetic mutation for Huntington's disease in presymptomatic individuals

• Published in: Journal of the International Neuropsychological Society 2002-11, Vol.8 (7), p.918-924
• Main Authors: BRANDT, JASON, SHPRITZ, BARNETT, CODORI, ANN MARIE, MARGOLIS, RUSSELL, ROSENBLATT, ADAM
• Format: Article
• Language: English
• Subjects: Adult; Asymptomatic; Basal ganglia; Basal Ganglia - pathology; Behavioral sciences; Chromosomes, Human, Pair 4 - genetics; Cognition Disorders - diagnosis; Cognition Disorders - etiology; Cognitive ability; Corpus Striatum - pathology; Genetic testing; Humans; Huntingtin Protein; Huntington Disease - complications; Huntington Disease - genetics; Huntington's disease; Huntingtons disease; Mental disorders; Mutation; Nerve Tissue Proteins - genetics; Neuropsychological Tests; Neuropsychology; Nuclear Proteins - genetics; Point Mutation - genetics; Presymptomatic dementia; Sensitivity and Specificity; Severity of Illness Index; Striatum; Trinucleotide Repeats - genetics
• ISSN: 1355-6177; 1469-7661
• DOI: 10.1017/S1355617702870060

A triplet repeat (CAG) expansion mutation in the huntingtin gene on chromosome 4 is responsible for Huntington's disease (HD). Presymptomatic genetic testing for this mutation has identified clinically normal persons who are virtually certain to develop this dementing illness if they live a normal lifespan. The present study sought to determine whether these “mutation-positive” persons have impairments in cognitive functioning. Seventy-five mutation-positive persons did not differ from 128 mutation-negative persons on tests selected for their sensitivity to early-stage HD. Interestingly, however, those with the mutation viewed themselves as more likely to develop HD than did those without the mutation. Among mutation-positive subjects, having a longer CAG repeat mutation was likewise not associated with cognitive impairment. However, being closer to estimated disease onset (a product of repeat length and parent's age at onset) was associated with selected cognitive impairments. When viewed in light of previous studies showing atrophy of the caudate nucleus and putamen in mutation-carriers who are close to onset but not those far from onset, these results suggest that subtle changes in brain and behavior may be detected shortly before subjects with the HD mutation develop sufficient signs and symptoms for diagnosis. Conceptual and methodological problems associated with the search for presymptomatic cognitive and behavioral indicators of dementing illness are discussed. (JINS, 2002, 8, 918–924.)