RESEARCH SUPPORT, NON-U.S. GOV'T
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Are cognitive changes the first symptoms of Huntington's disease? A study of gene carriers.

BACKGROUND: Huntington's disease is a neurodegenerative disorder due to an excessive number of CAG repeats in the IT15 gene on chromosome 4. The first symptoms are typically choreic movements or psychiatric disorders, whereas global cognitive decline generally becomes obvious later. This study was aimed at detecting early subtle cognitive deficits in asymptomatic gene carriers.

METHODS: As part of the testing procedure for predictive diagnosis of Huntington's disease, 91 asymptomatic at risk candidates had a neuropsychological examination, evaluating global efficiency, attention, memory (Wechsler memory scale and California verbal learning test), and executive functions.

RESULTS: The groups of carriers (n=42) and non-carriers (n=49) differed only on a few memory variables. When we considered the group of gene carriers as a whole, significant correlations emerged between the number of CAG repeats and (a) performance on several tests of executive functions, and (b) performance on the hard pairs associates of the Wechsler memory scale. Further analysis of performance on this memory subtest led to the division of the group of carriers into two subgroups, without any overlap. The performance of subjects without cognitive deficits (n=32) was similar to that of non-carriers on all tests. The subjects with cognitive deficits (n=10) differed from both carriers without cognitive deficits and non-carriers over a wide array of variables measuring executive functions and memory. Moreover, qualitative aspects of the performance of carriers with cognitive deficits in the California verbal learning test closely resembled those of patients diagnosed as having Huntington's disease.

CONCLUSION: This suggests that these subjects already have Huntington's disease, despite a total lack of motor and psychiatric signs. An ongoing follow up study is testing the prediction that they will develop the full range of symptoms of the disease earlier than carriers without cognitive deficits.

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