Cortex, Volume 115, June 2019,
Background: Memory for music has attracted much recent interest in Alzheimer's disease but the underlying brain mechanisms have not been defined in patients directly. Here we addressed this issue in an Alzheimer's disease cohort using activation fMRI of two core musical memory systems. Methods: We studied 34 patients with younger onset Alzheimer's disease led either by episodic memory decline (typical Alzheimer's disease)or by visuospatial impairment (posterior cortical atrophy)in relation to 19 age-matched healthy individuals. We designed a novel fMRI paradigm based on passive listening to melodies that were either previously familiar or unfamiliar (musical semantic memory)and either presented singly or repeated (incidental musical episodic memory). Results: Both syndromic groups showed significant functional neuroanatomical alterations relative to the healthy control group. For musical semantic memory, disease-associated activation group differences were localised to right inferior frontal cortex (reduced activation in the group with memory-led Alzheimer's disease); while for incidental musical episodic memory, disease-associated activation group differences were localised to precuneus and posterior cingulate cortex (abnormally enhanced activation in the syndromic groups). In post-scan behavioural testing, both patient groups had a deficit of musical episodic memory relative to healthy controls whereas musical semantic memory was unimpaired. Conclusions: Our findings define functional neuroanatomical substrates for the differential involvement of musical semantic and incidental episodic memory in major phenotypes of Alzheimer's disease. The complex dynamic profile of brain activation group differences observed suggests that musical memory may be an informative probe of neural network function in Alzheimer's disease. These findings may guide the development of future musical interventions in dementia.