Apathy: A very debilitating behavioral disorder that many patients with Parkinson’s disease have to face

It is not depression nor fatigue. Patients are less active, have less interests, and less empathy. It is such a change compared with their previous way of functioning that many caregivers cannot understand. It is often difficult to define, but it significantly impacts quality of life.

Clinically, apathy refers to a set of cognitive, behavioral and emotional features, such as reduced interest, lack of initiative and participation in the main activities of daily life, a trend towards early withdrawal from initiated activities, indifference and flattening of affect.

According to recent literature, the mean prevalence of apathy in Parkinson’s disease is almost 40%. Patients with apathy are on average slightly older than the non-apathetic patients, have slightly lower cognitive performance, more severe motor symptoms and an increased risk of co-morbid depression.

Research on apathy is relatively recent since it only became a topic of interest in the last quarter of the 20th century. This explains a certain unawareness of this syndrome, the lack of consensus on its definition and the lack of criteria for the clinical diagnosis. The first criteria were published by a group of experts led by the French psychiatrist, Philippe Robert, in 2009. They were updated in 2018. According to these criteria, apathy corresponds to a significant reduction in goal-directed activity in comparison with the previous level of functioning. It can manifest itself in the behavioral/cognitive (reduced level of activity, less persistence, less interest), emotional (less emotional reactivity and expression, less concern, less empathy) or social (less participation at social activities, less interest in social interactions) domains. At least two of these domains must be concerned. The disorder must be present for at least four weeks and be persistent.

Although these criteria help a lot to detect apathy, the diagnosis remains difficult due to the overlap with other conditions. The most common is depression. In Parkinson’s disease, apathy is also erroneously interpreted as anhedonia or fatigue. Are they independent or not? This issue remains open to discussion.

In Parkinson’s disease, apathy is usually related to impaired cognition. The more apathy is severe, the more overall cognition decreases. This impact on cognition is observed even at early stages of the disease. Moreover, apathy was shown to be a predictive factor for dementia and cognitive decline over time.

In spite of the frequency of this very debilitating non-motor syndrome and its negative impact on quality of life of both the person with Parkinson’s and the caregiver, treatments are currently poorly developed due to a lack of knowledge of the underlying mechanisms.

Recent research suggests that there is an overall dysfunction of the motivation brain network in people with Parkinson’s disease and apathy. The role of the mesocorticolimbic dopaminergic pathway is also frequently evoked. However, the mechanisms are far from being completely deciphered. They are probably more complex and involve other neuromodulation systems. The participation of the cholinergic and serotonergic systems has also been suggested.

In the last decade, some pharmacological and non-pharmacological treatments have been tested. The results were quite disparate and the level of evidence fairly low.

Currently, we need a better knowledge of how motivated behavior is produced to decipher which processes are disrupted in apathetic patients and how they relate to neuromodulation systems. Moreover, we need to have in mind that apathy is not unidimensional and that each dimension may involve different processes. The course of the disease has also to be considered since we know that disruption of neuromodulation changes with disease progression. All these aspects have to be considered if we want to develop effective treatments for apathy in Parkinson’s disease. Given the complexity of regulation of motivated behavior, it is likely that an approach that combines pharmacological treatment with cognitive-behavioral, emotional and environmental approaches will provide the opportunity to tailor therapies to the singular case of a person with Parkinson’s.

Kathy Dujardin, PhD presented at the 5th World Parkinson Congress in Kyoto, Japan. She is currently a neuropsychologist and Professor of Clinical Neuroscience in the Lille center of excellence in neurodegenerative diseases (LiCEND), at Lille University Medical Center.

Ideas and opinions expressed in this post reflect that of the authors solely. They do not reflect the opinions or positions of the World Parkinson Coalition®