Rheumatoid Arthritis Linked With Cognitive Impairment, but Review Finds Measurement Methods Vary

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Researchers hope these findings help develop methods to assess cognitive function in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) demonstrated greater cognitive function impairment compared with patients without RA, but the measurement methods vary, according to a review published in Joint Bone Spine.

Researchers who examined 16 different studies for the review found cognitive impairment has many different classifications.

“The most commonly used classification includes a clinical diagnosis of mild cognitive impairment (MCI), which focuses on memory functions and subjective difficulties, is confirmed by standardized psychological tests and an assessment of the patient’s normal everyday functioning, and is present in the absence of dementia,” the study authors said. “Other classifications are based on the presence of subclinical cognitive difficulties, confirmed by appropriately sensitive tests, that have worsened over the past year.”

The studies examined compared cognitive functioning between patients with and without RA to determine the severity of impairment as well as potential sociodemographic, clinical, and psychological factors that may affect the extent of cognitive impairment. Based on these factors, the authors say they hope to develop guidelines to assess cognitive function in patients with RA and identify variables that should be controlled for in future studies.

However, challenges remain. The studies used a variety of methods to measure cognitive impairment, which the authors said meant a network analysis was not possible. “Due to the inability to perform a network meta-analysis, it was decided to determine the effect sizes for studies which used the same measurement methods,” they wrote.

The studies covered a total of 921 patients with RA (812 women and 109 men) and 700 patients without RA; the mean age of participants ranged from 37.8 to 62.9 years. The studies were conducted in 10 countries: the United States, Canada, Spain, Egypt, Brazil, Greece, Turkey, South Korea, Hungary, and Romania.


The researchers used a meta-analysis using Cohen's d for the effect size and only included methods that were repeated in at least 2 studies and studies that gave information on at least 50% of the secondary variables of interest.

Six neuropsychological methods across the studies met the criteria, and were included in the following number of studies:

  • Mini-Mental State Examination (MMSE), 9
  • Montreal cognitive assessment test (MoCA), 3
  • Trail Making Test (TMT)-A, 3
  • TMT-B, 3
  • Wechsler Memory Scale (WMS) digits forward, 2
  • WMS digits backward, 2

According to the study, the effect sizes ranged from small to large, depending on the assessment method used. The presence of depression can affect results as well, the authors said.

The authors note that relying on physical tests may have resulted in false positive diagnoses of cognitive impairment.

“In the opinion of the authors of this text, the TMT-A and B are unsuitable for the assessment of cognitive functioning in this group of patients: the results obtained in this study with these instruments are based on the speed at which one connects consecutive points on a sheet, so they require that the participants have efficient motor functions,” the authors said. “Thus, clinical symptoms of RA—such as joint pain/degeneration—can significantly affect results and lead to false positive CI assessments.”

The results suggest following a diagnosis with therapeutic intervention and a complete diagnosis of cognitive function.

“The study pinpoints potential biases, lack of replication, and inconsistencies in reporting data as possible confounding factors and suggests further recommendations for assessment methods, research directions and clinical implications,” the study authors concluded.


Pankowski D, Wytrychiewicz-Pankowska K, Janowski K, Pisula E. Cognitive impairment in patients with rheumatoid arthritis: a systematic review and meta-analysis. Joint Bone Spine. Published online October 14, 2021. doi:10.1016/j.jbspin.2021.105298