Disease-specific profiles of apathy in Alzheimer’s disease and behavioural-variant frontotemporal dementia differ across the disease course

Apathy is one of the most prevalent and disabling non-cognitive symptoms of dementia. This loss of motivation and pervasive decline in goal-directed behaviour represents a core diagnostic feature of behavioural-variant frontotemporal dementia (bvFTD) and is also common in Alzheimer’s disease (AD). However, despite growing recognition of a multidimensional model, apathy has typically been examined as a unitary symptom. Here, we employed a cross-sectional design to characterise the multidimensional nature of apathy across syndromes and disease course. 92 participants (44 bvFTD, 20 AD, 28 controls) completed the Dimensional Apathy Scale (DAS) to quantify emotional, executive, and initiation apathy. Patients were divided into early and late stages based on time since symptom onset. All participants underwent structural MRI and voxel-based morphometry was used to identify neural correlates of apathy dimensions. In the early stage of the disease (< 5 years since onset), emotional apathy was greater in bvFTD than AD. In contrast, in the late stage (> 5 years since onset), executive apathy was greater in AD than bvFTD, although apathy was elevated across all dimensions compared to controls. Notably, apathy was observed in the absence of self-reported depression in 46.2% of patients, with no patients classified as depressed only. Neuroimaging analyses revealed both common and divergent prefrontal and subcortical neural correlates associated with apathy dimensions. Our results reveal differing profiles of apathy across the disease course, in AD and bvFTD, with distinct brain regions mediating these dimensions. These findings will inform the development of appropriate treatment targets to ameliorate the impact of apathy in dementia.