Although music therapy may engender clinical benefits in patients with neurodegenerative disease, the impacts of social and musical factors of such activities on socio-emotional and motor engagements are poorly understood. To address this issue, non-verbal behaviors of 97 patients with or without major cognitive impairment (CI) were assessed when listening to music or a metronome in front of a musician who was present physically (live) or virtually (video). Socio-emotional engagement was quantified as emotional facial expression production and gaze direction. Motor engagement was quantified as overall body motion and the production of rhythmic movements. In both groups, positive facial expressions were more frequent and rhythmic motor activities lasted longer with music than with a metronome, and during a live performance rather than a video performance. Relative to patients without CI, patients with CI moved less with music, expressed fewer emotions, and spent less time looking at the musician in the video condition and in the metronome condition. The relative reductions in motor and socio-emotional engagements in patients with CI might be markers of disease progression. However, the presence of a live partner induces older adults to engage emotionally and physically in musical activities emphasizing the relevance of using live performance as motivational levers during music therapy.