Apathy, empathy and depression in Alzheimer’s disease and frontotemporal dementia: Examining the constructs and white matter correlates

Abstract

AbstractBackgroundApathy and reduced empathy are commonly observed in Alzheimer’s disease (AD) and the core features of behavioural‐variant frontotemporal dementia (bvFTD). Depression is also prevalent in these syndromes. Recent work has proposed a multidimensional framework of apathy which includes three aspects of apathy: executive apathy (reduction of planning and organisation), emotional apathy (emotional indifference and decreased social engagement) and initiation apathy (reduced behaviour execution). These aspects can manifest as symptoms resembling empathy loss and/or depression. The extent to which these symptoms represent similar/divergent clinical dimensions, and their underpinning neural networks, remains unclear. This study investigated the interrelations between apathy, empathy loss and depression, and its white matter correlates, in AD and bvFTD.MethodThirty‐four AD and 51 bvFTD patients participated in the study. Items of the Dimensional Apathy Scale, Interpersonal Reactivity Index and Depression Anxiety Stress‐Depression Subscale were examined using Principal Component Analysis (PCA). White matter integrity and its associations with clinical components were measured via changes in fibre density and cross‐section using fixel‐based analysis.ResultThree components were identified through the PCA (Fig 1). Component 1 consisted of items assessing emotional apathy and empathy, while Component 2 included executive apathy items. Finally, all depression items loaded into Component 3. Regarding white matter correlates, Component 2 were strongly related to reduced white matter bundle density and cross‐section in fibres connecting the bilateral frontal lobe and subcortical structures (Fig 2), whereas Components 1 and 3 were associated with distributed white matter reductions.ConclusionThis study demonstrates that while emotional apathy and empathy loss share the underlying construct, executive apathy and depression are rather independent. White matter changes have strong implications for executive apathy, but not for emotional apathy, empathy and depression. Improved conceptualisation of these symptoms will be important for the development of personalised symptom‐specific therapies.