Apathy in Parkinson’s Disease: Defining the Park Apathy Subtype

Abstract

Apathy is a neurobehavioural symptom affecting Parkinson’s disease patients of all disease stages. Apathy seems to be associated with a specific underlying non-motor disease subtype and reflects dysfunction of separate neural networks with distinct neurotransmitter systems. Due to the complicated neuropsychiatric aetiology of apathy, clinical assessment of this invalidating non-motor symptom remains challenging. We aim to summarize the current findings on apathy in Parkinson’s disease and highlight knowledge gaps. We will discuss the prevalence rates across the different disease stages and suggest screening tools for clinically relevant apathetic symptoms. We will approach the fundamental knowledge on the neural networks implicated in apathy in a practical manner and formulate recommendations on patient-tailored treatment. We will discuss the Park apathy phenotype in detail, shedding light on different clinical manifestations and implications for prognosis. With this review, we strive to distil the vast available theoretical knowledge into a clinical and patient-oriented perspective.

Apathy in Parkinson’s Disease: Clinical Patterns and Neurobiological Basis

“…Overall, apathy has a prevalence of around 40% in PD for all stages [ 26 ]. It is estimated to affect around 30% of de novo PD patients, and prevalence increases along with PD progression up to 50% in the late stage [ 6 , 10 , 26 , 27 ].…”

“…Motivational and cognitive apathy, although not mutually exclusive, may be associated with distinct PD endophenotypes reflecting distinct Lewy pathology spreading in various brain regions and neurotransmitter systems [ 10 , 155 , 156 ]. Thus, animal models that mimic DA neuronal loss and the progressive formation of α-synuclein aggregates in various brain regions are needed.…”

“…This working group specified that symptoms should affect at least two of the three following dimensions of apathy: (i) diminished initiative, (ii) diminished interest and (iii) diminished emotional responsiveness. The prevalence of apathy increases along with disease progression [ 10 ]. In the early stage, the apathy–anxiety–depression triad mirrors the motor triad of PD [ 4 , 5 , 11 ].…”

Noradrenergic alterations in Parkinson’s disease: a combined 11C-yohimbine PET/neuromelanin MRI study

“…Apathy is a complex and multifactorial alteration of the internal and external drives of goal-directed behaviour. 80 It has been associated with dysfunctions of different neural networks supporting emotional/affective, cognitive and auto-activation circuits, 3 , 81 , 82 for which meso-cortico-limbic dopaminergic and serotoninergic lesions are thought to play a major role. The present study provides new insight into apathy pathophysiology and suggests that there is a role for noradrenergic alteration since we found a correlation between apathy and LC neuronal loss.…”

Gait initiation in Parkinson's disease: comparison of timing and displacement during anticipatory postural adjustments as a function of motor severity and apathy in a large cohort

“…Apathy is often overlooked in PD, and falsely attributed to cognitive decline or depression [ 25 ]. Despite its importance, its effect on gait and gait initiation specifically has not yet been examined [ 26 ].…”