Abstract Body

Huntington’s disease (HD) has historically been conceptualized as eminently a subcortical dementia due to basal ganglia degeneration. Accordingly, the cognitive domains assumed to be prototypically affected in HD are frontal-executive functions, attention and psychomotor speed. However, compelling evidence proves that, from the early stages of the disease, the pattern of brain atrophy characterising HD extends beyond the basal ganglia and also involves posterior-cortical and temporal regions. Thus, in HD, accurate neuropsychological examination reveals a complex cognitive phenotype not limited to frontal-striatal functions.

In addition to frontal-executive, attention and psychomotor speed disturbances, deficits of different severity at level of visuomotor integration, episodic and autobiographical memory, visual perception, mental rotation, arithmetic reasoning, social cognition and language can be also detected decades before the diagnosis of the disease.

The time of presentation and the pattern of progression of cognitive changes in HD show a relation with the disease burden. However, a marked heterogeneity is also frequently observed between patients sharing equivalent CAG repeat length, education and age. It suggest, that additional mechanisms rather than those driven by disease burden may also contribute to the complex cognitive picture of HD. Ultimately; the progression of cognitive deterioration along HD always associates a significant impact on functional independence to the point of dementia.

Here we review the cognitive aspects of HD, emphasising on the neural substrates of general-to-specific cognitive changes, the affected cognitive domains and processes, the neuropsychological assessment approaches, and the possible mechanisms participating in the differential expression of cognitive deterioration in the HD population.