Visual cognition as a marker of longitudinal disease progression in Huntington's disease

Visual cognitive impairment is common in Huntington's disease (HD), but its longitudinal trajectory and prognostic value remain unclear. We aimed to characterize changes in visual cognition in premanifest (preHD) and early manifest HD compared with healthy controls, and to determine whether baseline visual cognition is associated with clinical progression.

A total of 148 participants (78 controls, 39 preHD, 31 early HD) underwent annual assessments at baseline, 12, and 24 months. Visual cognition was assessed using an assessment protocol focused on attention, perception/processing speed, visuospatial ability, visual memory, and visuo-executive function. Disease burden was estimated using the CAG-Age Product (CAP). Linear mixed models examined group trajectories and tested whether baseline visual cognition predicted longitudinal changes in motor function (UHDRS), global cognition (MoCA), and quality of life (GENCAT).

Individuals with early HD showed faster decline in visual attention and visual perception/processing speed than controls, whereas preHD participants did not differ in overall rate of decline. However, visual memory worsened significantly in preHD as individuals approached estimated onset. Baseline visual cognition strongly predicted motor progression in preHD, with all domains associated with subsequent UHDRS worsening. In early HD, lower baseline visual attention and visuospatial abilities predicted greater cognitive decline. Quality of life remained stable overall, although baseline visuo-executive functioning predicted functional worsening in preHD.

Visual cognition may serve as a sensitive process-level marker of longitudinal change in HD, particularly in premanifest stages. Incorporating visual cognitive measures into multidomain progression models could refine early detection, stratification, and longitudinal monitoring in HD clinical research.