Abstract
Knowledge of the cognitive manifestation of Huntington's disease has burgeoned over the past two decades. Many studies from independent datasets have shown that cognitive impairment is evident before motor diagnosis, and annual cognitive decline is a robust marker of disease progression. Additionally, cognition is a critical concern to patients and families and is associated with meaningful outcomes, including functional capacity, driving, loss of accustomed work, and quality of life. In the past few years, Huntington's disease animal models of cognition have increased, preparing for preclinical experimental therapeutics with cognitive endpoints. A longitudinal analysis of cognitive variables was conducted with 559 gene-positive cases and 233 controls showing no signs of motor abnormalities over approximately a 3-year period. Results show statistically significant differences in rate of annual change for some cognitive variables, such that the cases group had worsening performance over time. These findings show that cognitive deterioration can be seen in persons with the Huntington's disease gene expansion with no overt motor signs or symptoms, suggesting that cognitive onset of Huntington's disease may precede motor.
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