Apathy and Huntington’s Disease: A Literature Review Based on PRISMA

Huntington’s disease (HD) is an autosomal-dominant, genetic neurodegenerative disease caused by an unstable expansion of the CAG triplet in the gene coding for Huntingtin. Onset can be at any age but generally occurs between the ages of 30 and 50.

In neuropathological terms, HD is essentially characterized by loss of medium spiny neurons in the caudate and putamen (1). Although atrophy starts in the striatum (2), imaging data show that cortical regions are also affected at an early stage (3, 4).

HD is characterized by motor, cognitive, psychiatric, and behavioral symptoms. The order of appearance of these symptoms varies between patients, but they inevitably lead to dementia. Nonmotor symptoms include executive dysfunction, memory impairments, attentional difficulties, disinhibition, depression, irritability, anxiety, and apathy (5).

Apathy seems to be the most common psychiatric symptom of HD. However, it is also present in many other pathological profiles. For example, it is highly prevalent in neurodegenerative disorders, such as Alzheimer’s disease (19%−88% of patients [6]) and Parkinson’s disease (7%−70% of patients [7]). In addition, apathy is associated with other neurological pathologies, such as stroke (8) and vascular dementia (9), as well as traumatic brain injury (10, 11). It can also be observed in psychiatric illnesses, most notably schizophrenia with negative symptoms (12). Some investigators have suggested that apathy is a behavior that can be related to normal aging (13).

Several studies (14–16) have shown that apathy is associated with poor quality of life among both patients and caregivers. However, these studies explored apathy by indicating only its presence/absence without a real description of the mechanisms underlying its appearance and its evolution as the disease progresses. While some definitions of apathy acknowledge that the symptom has cognitive, affective, and behavioral dimensions, the precise nature of the psychological processes underlying each dimension remains unknown. In our opinion, this lack of knowledge about the multidimensional aspect of apathy has negative consequences for clinical practice. In the present systematic review, we focus on different theoretical aspects of apathy. After highlighting current definitions, the tools used to assess apathy in several pathologies, and the relationship between apathy and other behavioral disorders, we examine the prevalence and characteristics of apathy in HD. Finally, we provide a critical review of the existing approaches to apathy. This critical review opens up new perspectives for improving our understanding of the multidimensional aspect of apathy and its considerable impact on the quality of life of patients with HD.

Current Definitions of Apathy

Apathy was first conceptualized by Marin in 1990 (17). According to Marin, apathy is characterized by a reduction in goal-directed cognition, associated with a lack of motivation in the following three dimensions: emotional (flat affect and emotional indifference), cognitive (decreased interest and lack of plans and goals), and behavioral (lack of effort, initiative, and productivity). This definition makes clear that apathy is a multifactorial concept with a variety of underlying mechanisms (10). Marin distinguished between apathy as a syndrome and apathy as a symptom of another syndrome. By doing so, he established a set of criteria for diagnosing apathy syndrome.

In 1994, Cummings et al. (18) suggested that apathy should be conceived as a loss of interest and motivation, with loss of initiative and flat affect. However, there is still no consensus on the conception of apathy. For example, Stuss et al. (19) stated that apathy cannot simply be attributed to a lack of motivation, because this is complicated to assess and requires observation and quantification of behaviors and affects. The authors therefore defined apathy as “an absence of responsiveness to stimuli internal or external as demonstrated by a lack of self-initiated action” (19). Here, apathy revolves around one key notion: initiation. For these authors, apathy is a set of related but separate states, and the clinical manifestations depend on the neural substrate and functional processes involved (cognitive, behavioral, and affective).

Based on Marin’s definition, Starkstein et al. (20) developed a set of diagnostic criteria for apathy in Alzheimer’s disease in order to distinguish clearly between depression and apathy, with a special emphasis on lack of motivation. The criteria were as follows: lack of motivation relative to the patient’s previous level of functioning or the standards of his or her age and culture as indicated by subjective account or observation by others; presence for at least 4 weeks during most of the day of at least one symptom belonging to each of the following three domains: diminished goal-directed behavior, diminished goal-directed cognition, and diminished concomitants of goal-directed behavior; the symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning; and the symptoms are not due to diminished level of consciousness or the direct physiological effects of a substance (20).

Levy and Dubois (21) put forward an alternative conception of apathy based on a cognitive model of behavior. Given that clinical manifestations of apathy are specific to lesions in the prefrontal cortex and basal ganglia, they deemed that apathy is a “behavioral observable syndrome” that manifests itself in a “quantitative reduction of self-generated, voluntary and purposeful behaviors.” They suggested that there are three underlying processes of apathy: emotional/affective (inability to associate affective/emotional signals with ongoing and forthcoming behaviors), caused by lesions in the orbital and medial prefrontal cortex or basal ganglia; cognitive (inability to elaborate a plan of action needed for ongoing and forthcoming behaviors), caused by lesions in the dorsolateral prefrontal cortex and caudate nucleus; and auto-activation (inability to activate thoughts or initiate actions). These authors suggested that there are many forms of apathy syndrome, the most severe corresponding to disturbance of the auto-activation process, which frequently results from lesions in the limbic and associative areas of the internal globus pallidus.

In line with Marin’s conception, Starkstein and Leentjens (22) focused on lack of motivation, linked to a reduction in goal-directed behaviors, and they included a temporal element in their diagnostic criteria. In order to establish a consensus in research and clinical practice, a new set of diagnostic criteria of apathy was developed (23, 24) (Box 1). These criteria had the same general structure as those of Starkstein et al. (25) based on Marin’s conception (26), and not only allowed apathy to be clearly distinguished from other concepts, but also considered all its dimensions (24).

More recently, a group of 23 experts (researchers, healthcare professionals, etc.) met to revise the diagnostic criteria for apathy in brain disorder. Using the Standard Delphi Methodology, they revised and developed the criteria in a two-step process: web surveys, followed by a consensus meeting (27) (Box 1). The modifications mainly concerned criteria A and B (subcriteria B1 and B3). More specifically, in criterion A, the term motivation was replaced with the term goal-directed behavior. According to Robert et al. (27), goal-directed behavior is a quantifiable term, unlike motivation. The second major modification concerned criterion B. Experts wanted to keep the same three-dimensional structure (behavior, cognition, and emotion). However, it was important to add a social aspect. Behavior and cognition have different underlying brain processes, but in clinical practice, apathy manifests itself in both cases as diminished observable activity (27). Thus, the expert group placed behavior and cognition in the same subcriterion (B1) and added a separate dimension: social interaction (subcriterion B3). According to the authors, this modification improved the assessment of apathy in both clinical research and everyday clinical practice. Another key change concerned criterion D, with the addition of the sentence “the symptoms (criteria A and B) are not exclusively explained or due to major changes in the patient’s environment.” This took account of the fact that some tragic events (e.g., terrorist attack) can lead to changes that may mimic apathy (27). By including a separate social interaction dimension covering spontaneous or stimulated social interaction, this new diagnostic criterion for apathy reflects an awareness of apathy’s multidimensional aspect. It provides as objective an assessment as possible, as it is based on aspects whose impairment can easily be described and observed.

The concept of apathy is also found in DSM, but it is only mentioned as a symptom of other pathologies (e.g., depression). The International Classification of Diseases makes no reference to apathy.

Defining specific criteria is very important. It avoids potential confusion between apathy and other clinical terms like abulia, anhedonia, depression, and learned helplessness. For example, the Oxford English Dictionary defines apathy as a lack of interest (cognitive aspect) or a lack of enthusiasm (affective aspect). However, abulia is defined as an absence of willpower or an inability to act decisively. This confusion has led to diagnostic errors. For example, in psychiatry, abulia is regarded as the severe form of apathy (24).

Apathy Assessment Scales

Many different instruments have been used to examine the presence and severity of apathy in psychiatric, neurological and neurodegenerative pathologies. Box 2 cites the apathy measures most commonly used in HD (5).

As can be seen, there is still only a limited choice of tests. In the majority of studies, apathy is evaluated with nonspecific tools. For example, the short version of the Problem Behaviors Assessment (PBA-s), the Frontal Systems Behavior Scale, and the Neuropsychiatric Inventory (NPI) are general tests for behavioral disorders, with only one or two items devoted to apathy. Other measures can assess apathy, but they are one-dimensional, simply providing an overall score to confirm or refute the presence of apathy (e.g., Apathy Evaluation Scale [AES] and 14-item Apathy Scale) (28). Another tool that is supposed to assess the different substructures of apathy is the Apathy Inventory, which was developed to collect comprehensive information about apathy’s presence in several brain pathologies (29). It takes several components of apathy into account: flat affect, loss of initiative, and loss of interest. This scale comes in three versions: clinician, caregiver, and patient. Its aim is to detect behavioral changes since disease onset. The clinician version takes the form of a semistructured interview (or even observation, in the case of prolonged hospitalization). The Apathy Inventory has consistent psychometric properties (30).

The Lille Apathy Rating Scale (LARS) also assesses different aspects of apathy. It was developed by Sockeel et al. (31), based on Marin’s conception of apathy. This scale includes 33 items covering nine domains: reduction in everyday productivity, lack of interest, lack of initiative, extinction of novelty seeking, motivation, blunting of emotional responses, lack of concern, poor social life, and self-awareness. It is administered in the form of a structured interview. It has a four-factor structure: intellectual curiosity, emotion, action initiation, and self-awareness. However, there has been no confirmatory analysis to validate these four factors (10). Internal consistency (α=0.80) and test–retest reliability (r=0.95) are satisfactory (30). A shortened version was developed and validated by Dujardin et al. (32). This version includes seven of the original nine domains (reduction in everyday productivity, lack of interest, lack of initiative, extinction of novelty seeking, motivation, blunting of emotional responses, and poor social life). The other two (lack of concern and self-awareness) were deleted because of their lack of sensitivity (33). This shortened version has acceptable internal consistency (α=0.73), good interrater reliability (r=0.95), and good test–retest reliability at 4 months (r=0.92) (11).

Despite its psychometric limitation, the LARS is one of the rare assessment tools to consider the multifactorial and multidimensional aspect of apathy. However, according to Radakovic et al. (34), the Apathy Inventory and LARS are good assessment tools for unidimensional apathy but not for multidimensional apathy. In order to remedy the lack of multidimensional scales, Radakovic and Abrahams (35) created a tool that is well adapted to the multidimensional aspect of apathy. The Dimensional Apathy Scale (DAS) was designed for persons with neurodegenerative diseases who have motor difficulties. To avoid the impact of motor deficits, none of the items rely on physical performances to assess the motor aspect of apathy. The structure of this scale was based on Levy and Dubois’s (21) conception, and it contains items taken from other scales (11). The authors conducted an exploratory factorial analysis based on 311 responses from healthy individuals. There were initially 45 items, but after deleting some items with a low saturation index, they came up with a version featuring 24 items evaluating the executive, emotional, and cognitive/behavioral dimensions of apathy. These items have good internal consistency (α=0.80). No study has yet been conducted with the scale’s target population (11). Although the exclusion of the motor aspect avoids confusion between pure motor difficulties and apathetic behaviors, the total exclusion of the motor dimension deprives users of information about the possible contribution of physical illness to the emergence of apathy (11). In several studies, researchers have argued that motor difficulties can contribute to the development of apathy and that there is a significant link between the two (36, 37). These authors suggested that physical disorders lead to a lack of interest in activities requiring physical performances. In this context, it is important to use scales that take account of the different factors that may contribute to the emergence of apathy (38).

However, the DAS remains one of the few multidimensional scales of apathy. For this reason, it was adapted and translated into French by M’Barek et al. (28). The French version (f-DAS) was validated with 223 healthy participants. Analyses indicated psychometric properties similar to those of the original version (35). The f-DAS has good validity and reliability, good internal consistency, and good discriminant validity against depression. A confirmatory factor analysis corroborated the three-factor model (28) of Radakovic and Abrahams (35).

In essence, the absence of a consensus on the nature of aspects of apathy and the different conceptions of apathy are reflected in several inconsistencies in the psychometric properties of all these assessment tools. To remedy these, we must have a single theoretical and conceptual basis on which to develop reliable and valid tools for measuring apathy (11).

Apathy and Other Neuropsychiatric Disorders

Psychiatric and behavioral disorders are not yet well documented in HD, even though researchers have known about them for a long time. These disorders are known to be responsible, at least in part, for the occupational and social disintegration that accompanies HD (39). They are also known to have a more harmful impact than the cognitive and motor symptoms on functional skills (40) and quality of life (41). In their literature review, van Duijn et al. (42) revealed a high prevalence of depression, anxiety, irritability, and apathy in HD. The frequency of these manifestations varied across studies from 33% to 76%, probably owing to disease progression. Obsessive-compulsive disorder (10%−52%) and psychotic disorder (3%−11%) were less frequent. Other psychobehavioral disorders are also reported in HD, including sexual behavior disorders (25%), which can give rise to everyday conflict (39). Eating disorders have also been reported, such as bulimia, snacking, or refusing food on account of delusions such as fear of poison (39). Furthermore, Snowden et al. (43) identified social behavior disorders such as egocentricity and lack of sympathy or empathy combined with mental toughness in patients with HD. Respect for shared social conventions can be disturbed in this population. For example, people with HD may make crude or obscene comments or engage in offensive behavior (44).

Apathy has always been addressed as a symptom of other pathologies (e.g., depression). Some authors consider apathy to be a symptom of depression. For example, Paoli et al. (45) suggested that depression is the most frequent symptom in HD, and that apathy is one of its clinical manifestations or somatic expressions. Authors sometimes include apathy in the same category as inactivity and weight loss. The boundaries between apathy and depression remained blurred for a long time, because they share common symptoms such as loss of interest and hypersomnia (35, 46). Over time, researchers realized that they are actually two completely different psychological entities: Apathy is a lack of motivation, whereas depression is a mood disorder. Marin (17, 26) noticed that the relation between apathy and depression varies according to the disease profile but also according to the individual’s profile. It should be noted that these two entities can frequently coexist. This confusion can lead to bias when estimating their frequency in different clinical pictures (47).

Apathy and Huntington’s Disease

As discussed above, apathy is one of the most common symptoms of HD. It has been investigated in several studies using different scales (e.g., NPI, PBA for HD [PBA-HD], and AES), as shown in Table 1.

Methods

We undertook a systematic review, based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This approach was chosen because of the lack of research and the heterogeneous nature of existing studies, as well as the lack of a comprehensive review of the literature on apathy and HD. This systematic review was conducted with two major databases; PubMed and PubMed Central. We manually searched reviews and checked reference lists to identify further relevant citations. We used the following key terms to search the databases: PubMed Central: (huntington[Abstract] AND apathy[Abstract]) and (huntington[Body - Key Terms]) AND apathy[Body - Key Terms]); PubMed: (huntington[Title/Abstract]) AND (apathy[Title/Abstract]) and (huntington[Text Word]) AND (apathy[Text Word]).

Inclusion and Exclusion Criteria

To be included in the present review, studies had to fulfill the following criteria: describing research among individuals with confirmed HD; involving patients aged 18 years and above; measuring apathy and other neuropsychiatric symptoms; drafted in the form of an article; and written in the English language. We excluded studies in the form of poster and paper presentations, editorials, and letters.

Data Extraction

In our systematic review, we extracted data on sample size, disease stage, apathy measure, other measures of neuropsychiatric problems, and major findings related to apathy.

Quality Appraisal

Owing to the nature of systematic reviews, we did not perform a quality appraisal. We did, however, highlight and discuss the methodological and clinical limitations of the studies we included wherever possible.

Results

The database searches yielded a total of 368 articles, which were reduced to 230 articles after duplicate suppression; removal of posters, letters, and other forms of study apart from original articles; and filtering for English language. Following the screening of titles and abstracts, 65 articles were eligible for review. After screening of the full-text articles, 25 were included in this systematic review (Figure 1).

Our review indicates that apathy is present at every stage of the disease. Studies of apathy in HD that were included are summarized in Table 1 (48–69). It is also the only symptom that gradually progresses, making it an excellent marker of disease progression (48, 57, 70). In their clinical review, McColgan and Tabrizi (71) confirmed that apathy is the most prevalent symptom in HD. According to these authors, this may be due to the absence of treatment for apathy, as other neuropsychiatric symptoms, such as depression and irritability, can be treated medically (antidepressants and antipsychotics).

First of all, as we can see in Table 1, the prevalence of apathy varied from study to study. This may have been due to several factors, such as place of recruitment, inclusion and exclusion criteria, disease severity (stage), and type of assessment tool. Nevertheless, all the authors agreed that apathy is a frequent neuropsychiatric manifestation in HD.

Second, it should be noted that patients rarely complained of apathy, although this does not imply that apathy is not disabling and does not have a negative effect on patients’ quality of life (16). Apathy is considered to be one of the most impactful disorders in terms of the quality of life of patients with HD and their caregivers (67). Patients have fewer social interactions and are less engaged in their activities and hobbies, while caregivers have a sense of isolation and the feeling of missing out on their lives (5). Apathy therefore has a substantial direct negative effect on the quality of life of both patients and caregivers. It also has a negative effect on family relations, as shown in the review by Good et al. (70), although it should not be forgotten that every patient is unique, in terms of the association of symptoms and the implications of the disease at family, social, and occupational levels. By the same token, the assessment of individual patients must take into account the social, cultural, and environmental dimensions of their psychological disorders. Patients each have their own life story, which obviously has an impact on the manifestation and maintenance of their disorders. By considering these different aspects, researchers and clinicians can avoid the neurobiologization of psychological functioning.

The findings of this systematic review show that research on apathy in HD is limited in terms of methods, approaches, and clinical findings. These are discussed below, along with suggestions for a new approach allowing apathy in HD and its underlying mechanisms to be better understood.

Limitations of the Current Concept of Apathy

As indicated earlier, despite its frequent occurrence in HD and its significant impact on quality of life, apathy is rarely studied and interpreted by taking its multidimensional nature and various underlying mechanisms into account.

Most investigators agree that apathy is a multidimensional entity. However, current conceptions tend to be applied in practice and research without any heed to the variety of apathy’s mechanisms. These conceptions are based on a descriptive and categorical approach, such as the one described in DSM, where patients are categorized according to the presence of symptoms and their severity and frequency. Several studies have adopted this kind of approach, particularly when it comes to tool choice and the interpretation of results. For example, in recent studies, the most common test was the PBA-HD or AES. However, the PBA was not specifically designed to evaluate apathy; it actually allows users to assess 11 different behavioral and psychiatric symptoms (depression, suicidal ideation, anxiety, anger/aggression, irritability, apathy, obsessive-compulsive behavior, perseverative thinking, delusions, hallucinations, and disoriented behavior). The AES only assesses severity and frequency.

Another limitation related to the categorical approach is the ambiguous relation between apathy and other psychological disorders like anhedonia, abulia, and, in particular, depression. Some authors consider apathy to be a symptom of depression. For Paoli et al. (45), depression is the most common symptom in HD, and apathy is one of the somatic expressions of depressive mood, belonging to the same category as inaction and weight loss. This confusion between apathy and depression is observed in neurological pathologies (10) and neurodegenerative diseases like Alzheimer’s disease (72). It should be noted that apathy can occur independently of depression in several pathologies, but also in the absence of depression. However, comorbidity is frequently observed (11). This dilemma surrounding diagnosis stems mainly from the existence of shared characteristics. According to diagnostic criteria, characteristics of apathy include lack or loss of interest; while according to DSM criteria, depression involves a loss of interest or pleasure. There is clearly an overlap between apathy and depression. It should be noted that these two psychological entities appear independently in 10% of patients with mood and personality disorders after closed head injury, and in combination in 60% of these patients (73). In their confirmatory factor analysis among patients with Parkinson’s disease, Kirsch-Darrow et al. (74) confirmed that apathy and depression share common signs. Their study revealed four factors: apathy, dysphoric mood, loss of interest or pleasure (reflecting the characteristic common to apathy and depression), and somatic. This goes against the idea that apathy is a sign of depression and highlights that apathy is a distinct entity.

In HD, the relation between apathy and depression is unclear. Naarding et al. (53) conducted a study among patients with HD to explore the relationship between these two behavioral dimensions. The main finding was that apathy and depression are two distinct entities and there is no clear correlation between them. The same results were reported by other authors such as Levy et al. (75). Contradictory results concerning the relation between apathy and depression probably stem from ambiguous definitions of their criteria and from the use of different approaches and diagnostic tools to assess apathy. Regarding this last point, most studies use tools based on categorical and descriptive approaches. There is no consideration of environmental, social, individual, and biological factors. Overall, these heterogeneous data findings raise a serious question about the validity of some study results.

According to Haslam et al. (76), depression is not a separate category but rather a dimensional entity. This raises several issues, the main one being the comorbidity of depression with other types of psychological disorders (77) such as apathy, and more notably loss of interest. Several authors have suggested conceiving of psychopathological disorders as patterns of dynamic interactions between symptoms (78–80). Put another way, we can conceive of psychopathological difficulties as a network of causally connected symptoms, such that if symptoms A and B are linked, then if symptom A is activated, symptom B will have a higher probability of being activated. These networks of symptoms are transdiagnostic, meaning that symptoms may be shared by other psychopathological problems. For example, Borsboom et al. (81) deemed that insomnia is common to both major depression and anxiety disorder and is induced by two different factors: feelings of guilt (for depression) or chronic anxiety (for generalized anxiety). Once insomnia is activated, it may in turn affect depressive mood (symptom of depression) or irritability (symptom of generalized anxiety).

Taken together, these circumstances suggest that apathy is not a latent entity that causes several symptoms, but rather a dimension where symptoms dynamically interact, and overlap too with other symptoms of other dimensional entities, notably depression. This highlights the importance of not focusing on a purely descriptive categorical approach, and not being limited to the assessment of pre-established symptoms. Rather, it involves assessing a wide array of symptoms and taking account of the heterogeneity of the mechanisms involved at different levels (biological, psychological, environmental, and sociocultural) in order to better understand comorbidities. To overcome categorical diagnostics such as DSM, the individuality and globality of the person should be considered, by attempting to gain more detailed and rigorous descriptions of his or her experiences, problems, difficulties, symptoms or specific complaints (82, 83).

Another typical limitation of the categorical approach is that it does not consider the existence of different and heterogeneous apathy profiles in HD. Apathy is not simply the sum of various specific and isolated symptoms whose clinical manifestations are limited to a specified brain area. Rather, it has several dimensions that combine to create different profiles, and its manifestations depend on interactions between symptoms and the nature of the mechanisms or factors involved. In their study, for instance, Strauss et al. (84) examined a sample of outpatients with schizophrenia to test the possibility that subgroups could be identified according to their negative symptoms. The authors ran cluster analyses of scores on the Scale for the Assessment of Negative Symptoms. Results revealed two different apathy profiles: one dominated by asociality, avolition, and anhedonia (apathy-avolition), and one that included alogia and blunted affect (diminished expressions). Authors also found that participants in the apathy-avolition subgroup were less likely to be in paid employment and to provide finished, high-quality work than the diminished expressions subgroup. They were also more likely to manifest symptoms of formal thought disorder and more likely to have poorer premorbid social adaptation in childhood. These data revealed the heterogeneity of apathy’s clinical manifestation in schizophrenia and the mechanisms and factors involved, as well as the various occupational and socioeconomic repercussions.

These findings point to the existence of different apathy profiles in HD, although to our knowledge, no study has yet explicitly investigated the complex and heterogeneous dynamics of apathy in HD, especially in the presymptomatic stage. It is important to identify the heterogeneous manifestations of apathy and the variety of underlying mechanisms, to ensure a better understanding of deficits and provide appropriate care and treatment.

All these circumstances suggest that it may be necessary to change the current thinking about psychopathological disorders in HD, notably apathy. It is important to make the assessment of apathy more systematic until the premanifest stage of the disease, then use a tool that assesses the different facets of apathy, instead of focusing solely on patients’ overall score and number of symptoms. Thereafter, a stringent method should be applied that details the complaints and factors involved in apathy manifestations without omitting to consider the different possible comorbidities and the overlapping of apathy symptoms with those of other disorders, particularly depression. This will allow for an accurate assessment of apathy and a precise identification of patients’ apathy profile to ensure better psychological care. This will be the next step in our research.

Conclusions

Apathy is common to many pathologies (psychiatric, neurological, and neurodegenerative), but regrettably its underlying mechanisms have been relatively unexplored. This has affected the development of apathy assessment scales and their psychometric properties. Apathy clearly has a multidimensional aspect, but its study continues to be based on a categorical and descriptive approach, even if a new multidimensional framework has been developed and applied in some research. For example, Arnould’s (11) study of apathy in patients with severe head trauma highlighted the diversity and heterogeneity of apathy profiles in these patients. Arnould also found that each profile was associated with different psychological processes. For example, the high apathy profile was significantly related to poor psychosocial functioning and a high level of subjective burden reported by caregivers, while the loss of initiative and interest profile was related exclusively to poor psychosocial functioning. This study assumed that apathy has four possible dimensions (cognitive, affective, motivational, and identity) and that each dimension is sustained by a variety of mechanisms (11).

Research needs to adopt this new model based on an integrative and multifactorial approach, thereafter generalizing it to other pathologies, which is what we are planning to do in our next study. At the theoretical level, we will aim to understand apathy, its various mechanisms, and its interrelations with other psychological difficulties in order to redefine and reconsider this symptom in HD. At the clinical level, this research will lead to a better understanding of apathetic behaviors related to HD and thus to more reliable and more sensitive assessments aimed at developing more effective psychological interventions targeting the relevant mechanisms.