Mild cognitive impairment and dementia in motor manifest Huntington's disease: Classification and prevalence

Objectives: To identify the characteristics and prevalence of mild cognitive impairment in patients with motor-manifest Huntington's disease (HD) and to propose a new mild cognitive impairment (HD-MCI) classification for HD. Methods: We included 307 motor-manifest HD participants from the ENROLL-HD study who completed the evaluation in four neurocognitive domains including executive functions, processing speed, language, and memory. Cognitive impairment in each domain was determined by age- and education-adjusted cutoffs (> 1.5 standard deviations below the mean). HD-MCI was defined as an impairment in at least one cognitive domain without a loss of functional independence (Function Independence Scale, FIS >= 85). Dementia (HD-Dem) was defined as at least two domains of cognitive impairment with functional impairment (FIS <= 80). Results: At the onset of motor symptoms, MCI was present in 84% and dementia in 5% of patients. After 5 years of motor symptoms, 24% of participants met the criteria for MCI and 69% for dementia. Executive dysfunction was the most common impairment, being present in 70% of participants, followed by slowed processing speed in 67%. Language impairment was reported in 55% and memory deficits in 53%. MCI subtypes were classified as Executive-predominant (executive impairment and slowed processing speed), Representational-predominant (impaired language and memory) and Mixed Executive-Representational. Executive-predominant MCI comprised 30%, Representational-predominant 15% and Mixed 55% of this cohort. Conclusion: MCI is highly prevalent in the early stage of motor-manifest HD. Three MCI subgroups are defined suggesting at the earlier stage of this disease the frontal-striatal-executive and/or the temporoparietal-representational functional network can be impaired.