Neuropsychological functioning and academic abilities in patients with juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a chronic rheumatoid disease that occurs in children under 16 and affects approximately 32.6/100,000 children in Western populations [1]. JIA is a disease that significantly alters the quality of life and can lead to a disability that can persist into adulthood [2]. A good way to understand the impact of this illness on the patients’ daily life is to investigate to what extent these children are integrated in school. Very few studies have explored this topic in the literature.

The involvement of the central nervous system (CNS) is not rare in paediatric rheumatic diseases, including in JIA [3]. The existing literature on JIA suggests the possibility of CNS damage due to the inflammation itself, to long-term medication or to pain linked to the disease. Indeed, certain types of JIA may result in compression of the upper cervical cord or the brainstem closely related to the development of neurological deficits [4‐6]. Beyond the risks caused by the inflammation itself, evidence has been put forward that neural impairments caused by the prolonged intake of medication - for example, corticosteroids, immunosuppressive drugs, or biotherapy are frequently prescribed as treatment independently or in combination [7‐9]. Moreover, one of the recurring symptoms common to the different clinical manifestations of JIA is chronic pain [10]. Extended experience of pain may saturate cognitive resources, impair neuroplasticity and deregulate the activity of several chemical and cellular neuromediators [11]. Electroencephalographic studies put forward that patients with JIA have reduced sleep quality [12, 13], while quality sleep has been shown to be essential for the consolidation of information in the long-term memory [14, 15]. Finally, social adjustment and regulation of emotions appeared to be fragile in JIA patients [16, 17]. Nonetheless, to the best of our knowledge, there has been no research into the social cognition abilities of JIA patients, namely emotion recognition or theory of mind.

Since school achievement depends to a great extent on cognitive functions [18], the aim of the present study was to contribute to the literature on paediatric rheumatoid disease by investigating the neuropsychological profile of JIA patients, in order to assess their potential academic achievement. In this respect, it has been shown that inclusive education is both academically and socially more complicated for children with JIA, resulting in a higher rate of failure than among their peers [19]. While the drop in academic results was first attributed to psychosocial factors due to the burden of chronic illness [20], very few studies have examined the real abilities of these students to succeed at school. To fill this gap, we assessed whether the neuropsychological functioning and academic skills children with JIA differ from those of the general population. For a comprehensive assessment, we explored six domains: general intellectual efficiency (i.e., logical reasoning), attention and executive functions (i.e., cognitive adaptive capacity), language functions (i.e., ability to understand and produce language), implicit and explicit memory (i.e., ability to encode, store and retrieve information in memory, and this, when the instruction is stated explicitly or not), verbal and nonverbal learning (i.e., learning words or figures), visual-spatial treatments (i.e., speed and quality of visuospatial information processing) and social cognition (i.e., ability to put oneself in the others’ shoes). Mathematics and reading tests were used to estimate the academic capacities of the children with JIA.

The study was pre-registered on Open Science Framework and all data are available on the following link: https://​osf.​io/​g63ak/​?​view_​only=​d00cd687af2e430c​a569074ae67445fe​

The two groups did not differ in terms of age, gender, socioeconomic background (Table 1), and there was no impact of these variables on the measures (all p > .05).

The aim of the present study is to contribute to the literature on childhood rheumatoid disease by thoroughly investigating the cognitive profile of the children with JIA and estimating the potential for academic achievement of JIA patients. Our sample comprised only non-systemic forms with a dominance of polyarticular and oligoarticular JIA forms, which may explain the over-representation of girls [32]. It is important to note that to the best of our knowledge, this is the first research to investigate the cognitive functions in non-systemic JIA patients. Our results highlighted preserved cognitive abilities, social cognition and implicit memory, and similar skills required to succeed academically in JIA patients and their peers. Importantly, this is the first time social cognition and implicit memory have been assessed in this population of patients. Indeed, an early social cognition, defined as the ability to understand other people’s points of view and feelings, predicts children’s subsequent school achievement and this pathway is mediatised by children’s level of social competence [33]. Moreover, implicit memory is also essential in learning and robust to cognitive disturbances. Research has shown preserved implicit memory in elderly and children with mental retardation [34, 35]. As the population of JIA children could have cognitive impairments, exploring implicit memory is essential. In order to thoroughly measure verbal and nonverbal implicit memory, we used experimental priming paradigms leading us to create two new tasks, a word completion task and a fragmented picture tests. The results of the cognitive profile and estimated academic achievement appear to be consistent since the cognitive functions are an important predictor of academic achievement, especially general intelligence and working memory [18]. Our results stand in apparent contradiction with literature that suggests impaired life conditions in adult patients with JIA. Three complementary interpretations may account for this discrepancy.

First, the developmental perspective according to which cognitive impairments develop later in a patient’s life should be taken into consideration. Our results are in line with a previous study indicating a normal intellectual quotient in children with systemic JIA [20], even though another body of evidence suggests potential neurocognitive impairment in these patients, whether directly or indirectly linked to the clinical manifestation of the disease process [3]. Specifically, the maturation of the CNS is subject to the consequences of various symptoms of JIA including the inflammation inherent in JIA [4‐6], the long-term medication [7‐9], reduced quality of sleep [12, 13], as well as the pain related to the disease [11]. In 2014, a review put forward the idea that children with JIA experience long-term changes to the CNS that could last into adulthood, resulting in lowering of the threshold of pain tolerance often associated with the inflammation [36]. In this perspective, a research assessed the cognitive aptitudes of 121 adult patients with rheumatoid arthritis [37]. Their results indicated that chronic pain, mediatised by depression, leads to impairment of cognitive functions, particularly the speed of information processing, reasoning ability, working memory and long-term memory. Importantly, these consequences depend on the duration and severity of the disease [38]. This set of findings is consistent with our results in assuming that while children with JIA are cognitively preserved, neuropsychological impairment may manifest itself later due to a lasting alteration of the CNS.

This hypothesis is supported by our descriptive data suggesting that some cognitive weaknesses begin already to appear in the JIA participants. Indeed, although the means comparison does not indicate a significant difference between the two groups, the number of participants having a deficit is higher in tasks requiring memory capacities and emotion recognitions. Yet, these two processes are essential for learning and academic success [15, 33]. If these descriptive results should be taken with caution at this point, they are nonetheless interesting. Indeed, the small size of our sample induces little statistical power and there is a risk of not detecting a difference between the two groups while existing in reality (i.e., statistical type 2 error). Furthermore, the comparison between JIA subgroups revealed that the enthesitis-related JIA group is more likely to underperform in mathematics compared to the oligoarticular JIA group. Future research should scrutinize in more depth the differences in prognosis for academic achievement as a function of the JIA subtypes.

Second, in addition to the neurological factors, the psychosocial determinants should be considered from a developmental perspective. Our results on the estimation of school achievement are only based on standardized literacy and mathematic tasks, which might not reveal the real school achievement of such children. It has been shown that, at most, 50% of the variance in academic outcomes was explained by the cognitive abilities of the students [18]. In other words, psychosocial factors may affect the deployment of the full cognitive capacities of JIA patients in a non-negligible way. Two factors are identified in the literature as particularly important. In the first place, the psychological resources required to cope with a chronic illness were investigated in JIA patients mostly based on the parents’ reports [16, 17]. The results mainly put forward that the burden of a chronic disease has a negative impact on emotional adjustment to social life [39], including school [20, 40]. Moreover, the constraints of coping with the disease and its symptoms means these children are more often absent from school than their classmates, disrupting both learning and their integration in the class Consequently, students with JIA are twice as likely to fail at school than their peers [19]. Next, a substantial literature on social psychology has highlighted subtle negative reactions from teachers towards the inclusion of students with disability [41, 42]. Yet the teacher’s perceptions have an important impact on students’ academic success [31], especially when the disability is invisible [43] as is the case with JIA. While academic achievement is an important predictor of well-being in adulthood [44], the quality of life of adults with longstanding JIA was found to hampered and was accompanied by a higher unemployment rate than in the general population [38]. All these studies support the hypothesis that JIA children face subtle psychosocial barriers to the full expression of their cognitive abilities in the long term. As our sample is small and did not allow us to test the above-mentioned developmental hypotheses, we strongly encourage further research to deepen the two developmental perspectives put forward. Research is also needed to more directly explore the factors that contribute to the emergence of elements that may threaten the quality of life (e.g., age, socio-economic status, perception of disability). Longitudinal methodologies would be particularly suitable since they would enable investigation of the precise factors leading to the deterioration.

Third, the clinical and socio-demographic characteristics of the patients with JIA may shed light on the results obtained in this research. Indeed, systemic forms of JIA are absent from our sample of participants. Yet, they are the most severe and most likely to affect the CNS due to the inflammation or the macrophage activations syndrome [45]. Thus, our results can only be relevant for non-systemic JIA. Future research should specifically focus on exploring the cognitive profile of systemic JIA, since it appears to be different in prognosis compared to other forms of JIA. Moreover, the majority of participants were on disease-modifying anti-rheumatic drugs and biotherapy at the time of the evaluation. If the latter might impact the SNC on the long term [9], it does not involve an important risk which might be the case for the corticosteroids. Indeed the corticosteroids were shown to disrupt the hippocampus and frontal lobe - brain regions responsible for memory, learning, as well as involved in cognitive and behavioural control [46, 47]. The low intake of corticosteroids in our sample may be related to the absence of systemic JIA. Finally, it should be noted that the patients were recruited on voluntary basis, mainly through the association of patients to which they are affiliated. Thus, the participants’ family motivation to participate in our research may have induced a recruitment bias. The sociodemographic data confirm that most of the children with JIA in our study came from upper-middle and upper class families. For this reason, it is difficult to extrapolate our results to all children with JIA, since our sample was small and the majority of the patients were recruited on a voluntary basis. While this did not bias our results as the JIA and the control groups were matched, it may have skewed the results by representing predominantly socially advantaged backgrounds contributing to better academic outcomes. Indeed, the family’s socioeconomic status is known to play an important role in a child’s academic achievement [48], and may explain why JIA children performed as well as their control peers in the academic tasks. Thus, following our first two interpretations, our results suggest that these children are less at risk of developing cognitive disorders later if they have such strong support from their families than most patients with JIA.

The results of this study revealed no significant differences between the JIA group and the control group, either the complete neuropsychological assessment or the tasks estimating academic performance. The two groups we compared were perfectly matched in age, gender, academic level (same-grade classrooms) and socioeconomic status. While our research indicates that children with JIA have every chance of developing positively, several studies have pointed out that, as adults, they are more prone to reduced quality of life [37], or even to developing cognitive impairments [36]. One of the interpretation put forward in this article is that medical (e.g., treatment), psychological (e.g., mental state related to the chronic pain), and sociocognitive (e.g., attitudes toward disability) factors may progressively crystallize long-term difficulties likely to weaken the quality of life of these patients. Our results emphasize the importance of supporting JIA patients and accompanying them throughout their education, which appears to be crucial for their future quality of life. Indeed, a deteriorated psychological state has been shown to have a negative impact on the cognitive functioning of people with JIA [36]. Further work is needed to better understand the development of the processes involved in the discrepancy between cognitive abilities in children and in adults with rheumatoid arthritis disease.