Introduction

Rheumatoid arthritis has a significant permanent functional impairment and disability (Erickson et al., 2017; Shah et al., 2017). Typically, the neuropsychological disorder does not require RA. Recent studies have shown that there may be a correlation between RA and cognitive impairment and that even mild cognitive impairment can interfere with daily working conditions for people with RA (Julian et al., 2012). While certain studies found a link between RA and cognitive impairment (Gorelick, 2010), others found no such correlation (Boyd et al., 2010). A large retrospective population-based study found that those who have a history of RA were considerably more likely to have experienced cognitive impairment over a 21-year period than those with other joint diseases (Wallin et al., 2012). Several mechanisms for RA memory impairment have been proposed, including a chronic systemic inflammatory process involving all organs. Neural tissue (Evren C, 2017; Kurne et al., 2009). Nevertheless, side effects associated with chronic systemic inflammation and autoantibodies can be accelerated (Pamuk et al., 2013) as well as the effects associated with neural tissue, in particular, glucocorticoid (Coluccia et al., 2008)and methotrexate (Pamuk et al., 2013) . Intact cognitive function in persons with chronic conditions, like RA, is essential to perform certain basic functions. Cognitive affected patients have increased behavioral issues, decreased adherence to medications and reduced quality of life (Appenzeller, Bertolo, & Costallat, 2004; Shin, Katz, & Wallhagen, 2012). This study was designed to investigate memory impairment in RA and to assess possible predictors.

PATIENTS AND METHODS

Study design

This is a case-control study done in Medical City Hospital from October 2017 till June 2018. Ethical approval was taken from the Medical Department, College of Medicine, University of Baghdad. Participant's consent was taken for inclusion in the study.

Participants

Patients group

Inclusion criteria

• Patients with RA and their age >16 years (Aletaha, Neogi, & Silman, 2010).

Exclusion criteria

• overlapping other inflammatory arthritis like systemic lupus erythematosus, systemic sclerosis, ankylosing spondylitis

• infection

• Tumors

• kidney and liver diseases

• neuropsychiatric problems

• medications known to affect cognitive function

Control group

Inclusion criteria, healthy controls with similar age and sex.

Data collection and entry

Data collection was done using questionnaires and interviews. Demographic and clinical features data included ,age, sex, body mass index, social class, disease duration, quality of life and medications used and disease activity measured using Clinical Disease Activity Index (CDAI) (Aletaha et al., 2005). Cognitive function was assessed by the Six-item Cognitive Impairment Test (6CIT) - Kingshill Version 2000 (Brooke & Bullock, 1999). The 6CIT uses an inverse score and questions are weighted to produce a total out of 28. Scores of 0-7 were considered normal and eight or more were significant cognitive impairment.

Statistical analysis

Continuous data were presented as Mean ± SD while categorical data as numbers and percentages. A chi-square test was used to measure the difference between categorical data. Univariate linear regression analysis then multiple linear regression analysis was used to assess the correlation between cognitive impairment test score with various variables in patients. SPSS v22 and Graph pad Prism v7 software for Windows were used. p-value < 0.05 was considered statistically significant.

Results and Discussion

A total of 130 patients and 130 healthy controls participated in the study. The mean age of patients was 48.9 ± 12.1 years and for controls was 48.5 ± 12.1 years (p= 0.794). Females were 100 (76.9%) for patients and 100 (76.9%) for controls (p=1.00). Other sociodemographic and clinical characteristics were shown in Table 1.

Prevalence of memory impairment was more in RA patients (47(69.1%) than controls 21(30.9%) [OR (95%CI)=2.939(1.632-5.294, p<0.001] Figure 1.

Age and prednisolone use were significantly and positively correlated with memory impairment (r = 0.346, p<0.001; r=0.224, p= 0.012 respectively) while the educational level was significantly and negatively correlated with CIT ( r=-0.489, p<0.001) as shown in Table 2.

This study evaluated the impact of RA on memory. It showed that memory impairment was more in RA patients than controls. RA increased the risk of having cognitive impairment with three folds. Also, increasing age and steroid use were significantly and positively correlated with cognitive impairment scores, while the educational level was significantly and negatively correlated with it. These findings are clinically important because early screening for cognition impairment may help early diagnosis and treatment, which will impact positively on health-related quality of life by improving adherence and response to treatment of RA.

The inflammation in the brain, high risk of cardiovascular comorbidity, immunosuppressive agents, and Glucocorticoid therapy (Hart, Wade, & Martelli, 2003; Shin et al., 2012)are possible causes of more memory deterioration in RA. Similar findings were reported by previous studies. (Appenzeller et al., 2004; Bartolini et al., 2002; Shin et al., 2012), who observed more memory drop in RA.

In the current study, we found a significant direct correlation between memory impairment with age, this in line with (Bartolini et al., 2002; Kim et al., 2017) which concluded that aging might contribute to memory drop. Also, low education, and use oral glucocorticoids were associated with memory impairment. These findings were in agreement with (Shin et al., 2012) who demonstrated that persons with less education, and use of oral glucocorticoid were more likely to be cognitively impaired. Similar finding was demonstrated by (Wolkowitz et al., 1990), who concluded that corticosteroids are related to memory problems.

In this study, there was no significant association between memory impairment and disease activity in RA patients. This was consisting of that reported by (Shin et al., 2012) ,who reported that disease severity was not a significant predictor of memory impairment in RA patients. On the other hand, this result was in contrast to (Kim et al., 2017), who found disease activity of RA contribute to memory impairment. These controversial studies findings may be due to different classifications of memory impairment and diverse assessment methods used and reflect the social and habits of a different society

This study had some limitation: small sample size, lack of follow up of RA patients to demonstrate an improvement in memory function following effective treatment of RA, and the third limitation was lack of new techniques of brain imaging such as Single-photon emission computed tomography, Positron emission tomography and Magnetic resonance imaging. However, up to the best of our knowledge, this is the first study among Iraq patients with RA that assessed memory impairment with strict inclusion and exclusion criteria.

Conclusions

In conclusion, RA patients had significantly higher memory impairment compared to control. Increasing age, low education, and using of steroids were significant predictors of memory impairment. There is no significant association between memory impairment and disease activity in RA patients. These findings suggest that memory impairment should be evaluated and assessed in RA patient. Extended evaluation of socioeconomic classes across patient's life is required and a large prospective study is needed to clarify the results.