What is Apathy?

Apathy: A Neuropsychiatric Syndrome

Apathy is a significant neuropsychiatric syndrome characterised by a quantitative reduction in goal-directed activity across multiple dimensions, including behaviour/cognition, emotion, and social interaction. It is defined as a diminished motivation not attributable to a diminished level of consciousness, cognitive impairment, or emotional distress. Some researchers define apathy as an absence of responsiveness to stimuli, demonstrated by a lack of self-initiated action, which can be affective, behavioural, or cognitive.

Apathy can manifest as reduced interest and participation in daily activities, a lack of initiative, a trend towards early withdrawal from activities, indifference, and a flattening of affect. It involves a lack of effort, initiative, and productivity (behavioural), decreased interests, lack of plans and goals, and lack of concern (cognitive), and flattened affect, emotional indifference, and restricted responses to important life events (emotional).

It's important to note that the definition of apathy has evolved, with earlier conceptualisations sometimes linking it to a lack of feeling or emotion. Contemporary views, however, often focus on the reduction of self-generated voluntary and purposeful behaviours, observable and quantifiable relative to an individual's previous behaviour.

Apathy is increasingly recognised as a common behavioural syndrome in psychiatric disorders and can be normal or pathological. When pathological, it can be a symptom of a neurological or psychiatric syndrome, an adverse effect of medication, or a syndrome in itself.

Prevalence

Apathy is highly prevalent across various neuropsychiatric populations, including those with dementia, mild cognitive impairment, Alzheimer's disease (AD), Parkinson's disease, frontotemporal dementia, cerebrovascular disease and stroke, and traumatic brain injury (TBI).

After traumatic brain injury (TBI), apathy is a common occurrence, with prevalence rates varying considerably in studies, ranging from 15% to 71%. Notably, apathy after TBI is generally unrelated to the time since injury and does not appear to have a significant association with either the age at injury or educational level. In individuals with severe TBI, deficits in motivation are a major neuropsychiatric symptom.

Minju Kim, "Apathy" (2020)

In dementia, apathy is one of the most frequent symptoms and its prevalence can range from 1.4% in older community-based individuals with normal cognition to as high as 6%, increasing over a 5-year period. Clinically significant apathy is also more common in mild cognitive impairment.

Apathy is also seen in the general population and in mild cognitive impairment. It can contribute to a failure to undertake daily activities and can lead to health problems or crises. The treatment of apathy is important for patients with Major and Mild Neurocognitive Disorder, schizophrenia, depressive disorders, and also for individuals with Post-Traumatic Stress Disorder, subjective cognitive decline, limbic and paralimbic tumours, personality disorders, TBI, stroke, small vessel disease, and ALS/MND.

Assessment

Apathy is assessed using various tools, with the Apathy Evaluation Scale (AES) being frequently employed. The AES has self-report (AES-S), informant report (AES-I), and clinician-rated (AES-C) versions. A modified self-report version has also been validated for use with Parkinson's disease patients. The AES-C is a measure of behavioural, cognitive, and emotional domains of apathy for the previous four-week period, often using a semi-structured interview with the patient and caregiver. Scores typically range from 18 to 72, with higher scores reflecting more severe apathy. A cut-off score of 37 or higher on the AES has been identified as indicating the presence of apathy following TBI. A score of 30 or higher on the AES-C is considered clinically significant apathy. The AES-I has shown good internal consistency and validity.

Other scales used to assess apathy include:

• Neuropsychiatric Inventory-Apathy subscale (NPI-AS)
• Lille Apathy Rating Scale (LARS), which has a caregiver-based version.
• Apathy Inventory (AI)
• Dementia Apathy Interview and Rating Scale (DAIR)
• Apathy Scale for Institutionalized Patients with Dementia Nursing Home version (APADEM-NH). This scale includes 26 items distributed in three dimensions: Deficit of Thinking and Self-Generated behaviors (DT), Emotional Blunting (EB), and Cognitive Inertia (CI).
• Person-Environment Apathy Rating (PEAR)
• Nonmotor Symptoms Questionnaire–Apathy subscore (NMSQ-AS)
• Dimensional Apathy Scale (DAS), which examines subtypes of apathy and allows for grading them. This scale relates to different manifestations of demotivation, considering both observable behavioural symptoms and cognitive deficits.
• Apathy-Motivation Index (AMI), a novel, brief tool to assess behavioural, emotional, and social facets of apathy.
• Starkstein's Apathy Scale (AS), a reduced version of the Marin's Apathy Evaluation Scale.
• DAPHNE, a six-domain scale that includes apathy.

The development of the AES involved literature, professionals, and authors' observations, although the involvement of participants in eliciting items and unreported observations have been noted as potential limitations. Fourteen items were also removed from the preliminary item pool.

Neuroanatomical Correlates

The neural bases of apathy are thought to rely on lesions in fronto-striatal circuits. Specifically, the prefrontal cortex and basal ganglia are frequently identified as key regions involved in apathy symptoms. Damage to areas such as the lateral prefrontal cortex, ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), insula, and white matter tracts connecting these regions has been implicated in apathy among the TBI population.

Studies using voxel-based lesion-symptom mapping (VLSM) have associated increased apathy symptoms with brain damage in limbic and cortical areas of the left hemisphere, including the anterior cingulate, inferior, middle, and superior frontal regions, insula, and supplementary motor area in individuals with penetrating TBI. Functional connectivity studies have also shown that increased apathy scores in TBI patients can predict decreased vmPFC-dorsal anterior cingulate cortex (dACC) functional connectivity.

Abnormalities within fronto-striatal circuits are consistently associated with apathy across different pathological conditions, and abnormalities within the inferior parietal cortex have also been linked. Damage to the ventral striatum, ACC, and basal ganglia may be associated with apathy. Increased apathy has been associated with damage to the supplementary motor area and insula, and to white matter in the left corona radiata and corpus callosum. The ventromedial prefrontal area is highlighted as playing a key role in stimulus-reinforcement learning, and its impairment may underlie some behavioural changes following damage, potentially including apathy. Changes in brain networks due to the direct effect of the lesion (diaschisis) are also relevant to understanding the functional consequences of TBI. Much of what we know about neural correlates of apathy relates to post-stroke conditions.

Apathy vs. Depression and Anhedonia

It is crucial to distinguish apathy from depression, although they can frequently co-occur. While both conditions can present with reduced interest in activities, apathy is characterised by a primary lack of motivation, whereas depression typically involves dysphoria or low mood. Some symptoms like fatigue, loss of energy, and diminished ability to think or concentrate can be common to both, especially in the post-acute period after severe TBI. However, a key distinction is the absence of symptomatic dysphoria in an apathy syndrome. Apathy may occur either alone or in association with depression following head injury. 

The nosological relationship between apathy and anhedonia (the inability to experience pleasure) depends on how apathy is conceptualised. If apathy is considered a state of absence of feeling and emotional sensitivity, anhedonia could be a symptom of apathy. However, if apathy is seen as diminished motivation, anhedonia may not be a necessary diagnostic criterion. Apathy presents as an overall lack of motivation based on decreased goal-directed behaviour or thoughts, as well as affective flattening or indifference, whereas anhedonia specifically involves a lack of desire to pursue a reward or pleasure from a reward.

Diagnostic Criteria

Diagnostic criteria specific for apathy in neurocognitive disorder (NCD) are considered important for research and clinical practice. Initial diagnostic criteria for apathy as a syndrome, applicable independently of its aetiology, have been proposed.

The 2018 international consensus group revised the diagnostic criteria for apathy in brain disorders, defining it as a quantitative reduction of goal-directed activity either in behavioural, cognitive, emotional or social dimensions compared to the patient's previous level of functioning (Criterion A). Criterion B requires the presence of at least two of three dimensions for at least four weeks and present most of the time: diminished initiative, diminished interest, and diminished emotional expression/responsiveness. Criterion C states that these changes must cause significant functional impairment and Criterion D specifies that they should not be exclusively explained by other etiologies. These criteria provide a framework for defining apathy as a unique clinical construct in NCD for diagnosis and further research.

Consensus criteria for apathy in NCD have undergone amendments, including consistent use of "diminished" to describe dimensions and replacing "domain" with "dimension" for consistency across brain diseases. The severity criterion now explicitly states that behaviours should represent a change from the patient's usual behaviour. In assessing apathy in NCD, greater weight may need to be given to caregiver and clinician reports due to potential diminished insight in patients.

Diagnostic criteria for apathy following stroke also exist, defining it as a quantitative reduction in goal-directed behaviours occurring in the cognitive/behavioural, emotional, or social domains, relative to previous functioning and reported by the individual or others. The presence of at least two of these dimensions for at least four weeks is required.

Challenges and Future Directions

Defining and treating apathy remain challenging due to the lack of a universally accepted definition and gold standard measurement. The use of arbitrary cut-offs on various scales has been common, highlighting the need for specific diagnostic criteria. The multidimensional nature of apathy, with behavioural, cognitive, and emotional components, further complicates its understanding. There is a need for a uniform operational definition and standardised outcome measures specific to apathy to enhance comparison among treatments.

Research is ongoing to better understand the neurobiological and psychological underpinnings of apathy to develop targeted and effective rehabilitation strategies. This includes investigating the mechanisms underlying each dimension of apathy. Future research should focus on building a consensus on the definition and diagnosis of apathy, further refining the psychometric properties of assessment tools, and examining the overlap with other conditions. Better stroke and apathy subtyping is needed to benefit epidemiological and outcome research. Longitudinal studies using tools like web-based TBI exposure surveys are being developed to enhance understanding of the long-term effects of brain trauma and the development of behavioural symptoms like apathy.

Potential Treatments

Treating apathy following TBI and other conditions is challenging, and research on effective interventions is ongoing. A systematic review is being conducted to synthesise evidence for the pharmacological management of neurobehavioural symptoms post-TBI, including apathy. Interventions range from pharmacological approaches using dopamine agonists, acetylcholinesterase inhibitors, and psychostimulants to psychological therapies. However, a systematic review found limited evidence for the effectiveness of specific interventions for apathy in the TBI population, highlighting the need for more methodologically rigorous studies. There is some support for the use of methylphenidate, SSRIs, and cholinesterase inhibitors for apathy in certain conditions, and repetitive TMS may hold promise. Management strategies for TBI survivors need to be tailored to individual needs, and novel therapy choices may arise. Non-pharmacological interventions are also being explored. A holistic approach to treating apathy is advocated, including comprehensive assessment, treating underlying causes, and differentiating from depression.