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Genetic risk for RA associated with early cognitive symptoms in children
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Having an increased genetic risk for rheumatoid arthritis is associated with demonstrating hyperactivity and inattention symptoms from ages 4 to 16 years, as well as lower total IQ and IQ performance at 8 years, according to data published in JAMA Network Open.
“It has long been recognized that there are elevated rates of cognitive and psychiatric phenotypes in patients with RA,” Hannah J. Jones, PhD, of the University of Bristol in the United Kingdom, and colleagues wrote. “For example, a number of studies have reported evidence of specific areas of cognitive difficulty in adults with RA, including poorer performance in tests of verbal IQ, attention, and memory. ... Despite the robust evidence of cognitive deficits and increased presence of some psychiatric disorders in people with RA, the mechanism underlying these associations is unknown.”
“Delineating the significance of each of these associations in patients with active disease is difficult owing to their health status and clinical management,” they added. “However, general population studies examining the effects of risk factors for RA provide an opportunity to study alternative explanations for these associations while excluding RA disease-related mechanisms.”
To evaluate whether genetic risk for RA is linked to cognitive and psychiatric symptoms in children and adolescents, Jones and colleagues analyzed data from the Avon Longitudinal Study of Parents and Children cohort. All children included in the cohort have undergone detailed longitudinal health assessments since birth, with data available through a searchable dictionary and variable search tool. The researchers collected clinical and questionnaire data periodically from Sept. 6, 1990, onward, with analyses performed from August 21, 2017, to May 21, 2018.
Genetic data were available for 7,977 children and adolescents in the cohort, for whom the researchers generated polygenic risk scores for RA using genome-wide association studies. Cognitive measures taken during clinical visits in the Avon Longitudinal Study of Parents and Children included IQ, working memory, verbal learning, processing speed, problem solving, selective attention and attentional control. Children and adolescents in the cohort were also measured for anxiety, depression, negative symptoms, psychotic experiences, attention-deficit/hyperactivity disorder and hyperactive and inattentive symptoms.
Nine of the 7,977 children and adolescents included in the study had a known diagnosis of RA by the age of 22 years.
According to the researchers, increased polygenic risk scores for RA were associated with lower total IQ (beta = –0.05; 95% CI, –0.07 to –0.02), performance IQ (beta = –0.03; 95% CI, –0.06 to –0.005) and verbal IQ (beta = –0.05; 95% CI, –0.08 to –0.02) at age 8 years. Higher genetic risk for RA was also linked to hyperactivity and inattention symptoms from ages 4 to 16 years, with the strongest evidence of association demonstrated at age 13 years (OR = 1.25; 95% CI, 1.12-1.39). However, there was little data supporting an association between the RA genetic risk and other cognitive measures or psychopathology.
“The associations observed within the current study have implications in terms of the clinical assessment and management of RA,” Jones and colleagues wrote. “Overall, RA is currently conceptualized as a multisystem connective tissue disorder. The current results, however, suggest that CNS impacts should also be considered a core and primary component of RA, especially in the domain of cognition. Furthermore, they support the view that clinically it is important to assess and monitor cognitive impairment in patients with RA, especially as cognitive factors can affect activities of daily living and individuals’ overall level of functioning.” – by Jason Laday
Disclosure: Jones reports no relevant financial disclosures.
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