Apathy in Alzheimer's disease

Apathy is a debilitating syndrome associated with many neurological disorders, including several common neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, and focal lesion syndromes such as stroke. Here, we review neuroimaging studies to identify anatomical correlates of apathy, across brain disorders. Our analysis reveals that apathy is strongly associated with disruption particularly of dorsal anterior cingulate cortex (dACC), ventral striatum (VS) and connected brain regions. Remarkably, these changes are consistent across clinical disorders and imaging modalities. Review of the neuroimaging findings allows us to develop a neurocognitive framework to consider potential mechanisms underlying apathy. According to this perspective, an interconnected group of brain regions – with dACC and VS at its core – plays a crucial role in normal motivated behaviour. Specifically we argue that motivated behaviour requires a willingness to work, to keep working, and to learn what is worth working for. We propose that deficits in any one or more of these processes can lead to the clinical syndrome of apathy, and outline specific approaches to test this hypothesis. A richer neurobiological understanding of the mechanisms underlying apathy should ultimately facilitate development of effective therapies for this disabling condition.

This study was designed to establish the validity and reliability of the apathy inventory (IA), a rating scale for global assessment of apathy and separate assessment of emotional blunting, lack of initiative, and lack of interest. Information for the IA can be obtained from the patient or from a caregiver. We evaluated 115 subjects using the IA, consisting of 19 healthy elderly subjects, 24 patients with Mild Cognitive Impairment (MCI), 12 subjects with Parkinson's disease (PD) and 60 subjects with Alzheimer's disease (AD). Internal consistency, item reliability, and between-rater reliability were high. A test-retest reliability study demonstrated that caregiver responses to IA questions were stable over short intervals. A concurrent validity study showed that the IA assesses apathy as effectively as the Neuro Psychiatric Inventory apathy domain. In the caregiver-based evaluation, AD subjects had significantly higher scores than controls, both for global apathy score and for the lack of interest dimension. When the AD patients were subdivided according to diagnostic criteria for apathy, apathetic patients had significantly higher scores than non apathetic patients. With the patient-based evaluations, no differences were found among the AD, MCI and control groups. The scores in the patient-based evaluations were only higher for the PD group versus the control subjects. The results also indicated that AD patients had poor awareness of their emotional blunting and lack of initiative. The IA is a reliable method for assessing in demented and non-demented elderly subjects several dimensions of the apathetic syndrome, and also the subject's awareness of these symptoms. Copyright 2002 John Wiley & Sons, Ltd.

Apathy is a debilitating but poorly understood disorder characterized by a reduction in motivation. As well as being associated with several brain disorders, apathy is also prevalent in varying degrees in healthy people. Whilst many tools have been developed to assess levels of apathy in clinical disorders, surprisingly there are no measures of apathy suitable for healthy people. Moreover, although apathy is commonly comorbid with symptoms of depression, anhedonia and fatigue, how and why these symptoms are associated is unclear. Here we developed the Apathy-Motivation Index (AMI), a brief self-report index of apathy and motivation. Using exploratory factor analysis (in a sample of 505 people), and then confirmatory analysis (in a different set of 479 individuals), we identified subtypes of apathy in behavioural, social and emotional domains. Latent profile analyses showed four different profiles of apathy that were associated with varying levels of depression, anhedonia and fatigue. The AMI is a novel and reliable measure of individual differences in apathy and might provide a useful means of probing different mechanisms underlying sub-clinical lack of motivation in otherwise healthy individuals. Moreover, associations between apathy and comorbid states may be reflective of problems in different emotional, social and behavioural domains.