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Objective information about the onset and progression of cognitive impairment in Huntington's disease (HD) is very important in the light of appropriate outcome measures when conducting clinical trials. Therefore, we evaluated the progression of cognitive functions in HD patients and asymptomatic carriers of the HD mutation (AC) over a 2.5-year period.We also sought to detect the earliest markers of cognitive impairment in AC.A prospective study comparing HD patients, clinically asymptomatic HD mutation-carriers (AC) and non-carriers (NC). These groups were examined three times during a period of 2.5 years. At baseline the study sample consisted of 49 subjects. Forty-two subjects (19 HD patients, 12 AC and 11 NC) completed three assessments. A battery of neuropsychological tests measuring intelligence, attention, memory, language, visuospatial perception, and executive functions was performed.The performance of HD patients deteriorated on the following cognitive tests: Symbol Digit Modalities Test (SDMT), Stroop Colour and Word, Boston Naming Test (BNT), Object and Space Perception and Trail Making Test-B. Longitudinal comparison of AC and NC revealed that performances on SDMT, Block Span, Digit Span Backwards, Hopkins Verbal Learning Test (learning and delayed recall) and Conditional Associative Learning Test are impaired in AC.Tasks measuring mainly attention, object and space perception and executive functions adequately assess the progression of HD disease. Other cognitive functions do not significantly deteriorate. Furthermore, problems in attention, working memory, verbal learning, verbal long-term memory and learning of random associations are the earliest cognitive manifestations in AC.