Elsevier

Cortex

Volume 103, June 2018, Pages 350-359
Cortex

Behavioural neurology
Apathy in Alzheimer's disease and frontotemporal dementia: Distinct clinical profiles and neural correlates

https://doi.org/10.1016/j.cortex.2018.03.019Get rights and content

Abstract

Objective

Apathy is the most prevalent and disabling non-cognitive symptom of dementia and affects 90% of patients across the disease course. Despite its pervasiveness, how apathy manifests across dementia syndromes and the neurobiological mechanisms driving these symptoms are poorly understood. Here, we applied the multidimensional ABC model of apathy, which recognizes Affective, Behavioural and Cognitive apathy, in Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD).

Methods

One hundred and twenty-two patients (53 AD; 69 bvFTD) were included. Informants completed the Neuropsychiatric Inventory (NPI), Cambridge Behavioral Inventory and Disability and Dementia scale to quantify Affective, Behavioural and Cognitive apathy. All patients underwent structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) was employed to identify brain regions correlated with increased Affective, Behavioural and Cognitive apathy.

Results

On the NPI, 60% of AD and 84% of bvFTD patients had some degree of apathy, but bvFTD had more severe and more frequent symptoms than AD. Importantly, bvFTD patients had higher affective and cognitive apathy whereas AD had higher cognitive apathy only. Neuroimaging analyses revealed that affective apathy was associated with the ventral prefrontal cortex; behavioural apathy with the basal ganglia; and cognitive apathy with the dorsomedial prefrontal cortex. Finally, affective and behavioural apathy significantly predicted carer burden.

Conclusions

Our results support the notion that apathy is multidimensional and manifests differently across dementia syndromes. Thus, novel interventions which target these divergent mechanisms will be necessary to improve motivation and goal-directed behaviour in people with dementia.

Section snippets

Background

Apathy is the most prevalent and disabling non-cognitive symptom of dementia (Pagonabarraga et al., 2015, Savva et al., 2009), affecting up to 90% of individuals with dementia over the disease course (Steinberg et al., 2008, van Reekum et al., 2005). This loss of motivation severely limits the ability to function independently and to carry out activities such as basic hygiene, cooking, and maintaining social relationships. Moreover, presence of apathy in dementia is associated with functional

Participants

In total, 122 dementia patients were recruited – 69 bvFTD and 53 AD – from FRONTIER, the younger onset dementia research clinic in Sydney. All patients were assessed by an experienced behavioural neurologist and underwent neuropsychological assessment, structural brain magnetic resonance imaging (MRI) and had a reliable informant available. Diagnosis was determined according to current international consensus criteria (McKhann et al., 2011, Rascovsky et al., 2011). Exclusion criteria were:

Results

No significant differences in age, education or sex were observed across groups (all p values > .05; Table 1) and patient groups were matched for disease duration (p = .471). In line with previous findings, functional impairment (clinical disease stage on the FRS) was greater in bvFTD than AD (p < .001), with bvFTD patients rated as severe whereas AD patients were rated as moderate (Mioshi et al., 2010). Both patient groups showed significant cognitive impairment relative to controls on the ACE

Discussion

We have revealed here, that both the severity and nature of apathy is significantly different in AD and bvFTD. Although a relatively similar proportion of patients with AD and bvFTD show apathy on the NPI, in AD, the apathy was less frequent and less severe than in bvFTD. When we examined the different aspects of apathy applying the ABC model (Levy and Dubois, 2006, Marin, 1991), divergent profiles emerged: severe cognitive apathy in AD; severe affective and cognitive apathy in bvFTD; and

Funding sources

This work was supported in part by funding to ForeFront, a collaborative research group dedicated to the study of frontotemporal dementia and motor neuron disease, from the National Health and Medical Research Council (NHMRC) (APP1037746) and the Australian Research Council (ARC) Centre of Excellence in Cognition and its Disorders Memory Program (CE11000102). In addition, this study was supported by NHMRC Project Grant (APP1121791). FK is supported by an NHMRC-ARC Dementia Research Development

Conflict of interest

The authors have no conflicts of interest to declare.

Acknowledgements

The authors are grateful to all the patients and their families for supporting our research.

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