Rheumatologic conditions are diseases that affect the joints and connective tissues. Individuals with these conditions may experience cognitive symptoms. This article will discuss the cognitive and neural consequences of some common types of rheumatologic illnesses, including fibromyalgia, chronic fatigue syndrome, systemic lupus erythematous, and Sjögren’s syndrome.



Fibromyalgia is defined as widespread joint pain and the presence of pain in at least 11 of 18 trigger points (assessed by a clinician who applies finger pressure to these points) without a clear marker of pathology (1, 2). It occurs more commonly among females than males. The etiology of fibromyalgia  is unknown. Studies have identified reduced blood flow in the thalamus and pontine tegmentum of the brain, but similar findings have been found in those with psychiatric disorders. Consistent with this, emotional problems, such as depression and anxiety, and a history of trauma are common among people with fibromyalgia  (2).

Individuals with fibromyalgia  may experience impairments in attention, working memory (ability to mentally hold and manipulate information), memory, and executive functions (higher-order cognitive abilities such as inhibition and rapid word generation). Such deficits may be due to involvement of brain regions that subserve cognitive processes during painful stimulation, such as the anterior cingulate cortex, posterior parietal lobe, and dorsolateral prefrontal cortex (1). However, their subjective complaints are generally out of proportion of the impairments detected upon objective testing. Some investigations have found weaker performances on measures of effort in individuals with fibromyalgia  than healthy controls (2).


Chronic fatigue syndrome

Chronic fatigue syndrome is defined by longstanding (greater than six months) fatigue which is not resolved with rest, as well as the presence of four of eight symptoms (including muscle ache, joint pain, subjective cognitive complaints, sore throat, new headache, nonrestorative sleep, postexertion malaise, and swollen lymph glands) (1, 2). It occurs more commonly among females than males. The etiology of chronic fatigue syndrome is unclear (2).

In terms of cognitive symptoms, individuals with chronic fatigue syndrome may have difficulty with processing information quickly, attention, working memory, learning and memory, and executive functions. Reduced overall brain volume, abnormalities in the white matter (connections between brain regions), and decreased blood flow globally and in the frontal and occipital lobes of the brain have been identified in individuals with chronic fatigue syndrome, compared to healthy controls (1). Many of these results are similar to those found in psychiatric samples. As with fibromyalgia , subjective cognitive complaints are usually greater than what is found in objective assessment. Individuals with chronic fatigue syndrome who find their condition debilitating are found to have weaker performances on effort testing. Chronic fatigue syndrome is also associated with mood disorders.


Medically unexplained syndromes

People with a history of trauma and/or emotional distress are more susceptible to developing medically unexplained physical symptoms, such as fibromyalgia  and chronic fatigue syndrome. Psychological stress and trauma can cause pathological changes in the immune and endocrine systems as well as brain structure and function. For example, depression and post-traumatic stress disorder (PTSD) are associated with lower immune functioning. Excessive stress hormones may contribute to brain cell loss in the hippocampus (brain region essential for memory formation) among individuals with PTSD (2). The cognitive impacts of fibromyalgia  and chronic fatigue syndrome may be explained by the interaction between psychological and biological pathways.


Systemic lupus erythematous

Systemic lupus erythematous (SLE) is an autoimmune disorder (one’s immune cells attack their own body tissues as if they are foreign) that can affect many different bodily organ systems, including the joints, skin, kidney, heart, lungs, blood vessels, and the brain. Neurological and psychiatric symptoms (NPSLE) occur in 21-95% of lupus cases, but only 13-38% of these events are attributable to lupus. Other factors may cause neuropsychiatric events in patients with lupus, such as drugs, metabolic abnormalities, or infections. NPSLE encompasses a wide range of neurological and psychiatric signs, including cerebrovascular disease, seizure disorder, movement disorder, mood/anxiety disorder, psychosis, polyneuropathy, and cognitive impairment (3). Cognitive symptoms may include difficulties with processing speed, working memory, visual learning, and memory. These neuropsychiatric symptoms can be either transient or chronic (4).

Neuropathology of lupus may arise from 1) small vessel disease leading to blockage or bleeding in the brain and/or 2) abnormal autoantibodies targeting brain cells. Magnetic resonance imaging (MRI) may reveal white matter hyperintensities (lesions in the connections between brain cells), which are more common in the frontal-parietal and perisylavian regions, although it may be difficult to distinguish between lupus and multiple sclerosis (MS) and other vascular diseases in MRI findings. Corticosteroids and immunosuppressive medications are used to treat lupus. There are mixed results in the literature regarding the cognitive benefits of steroid treatments (4).


Sjögren’s syndrome

Sjögren’s syndrome (Sjögren’s syndrome) is a systemic autoimmune disorder affecting the exocrine system or moisture-producing glands (e.g., dry eyes and mouths). It can occur as a primary disorder or be associated with other rheumatologic diseases, such as lupus. Neurological symptoms (affecting the brain, spinal cord, and/or cranial nerves) occur in approximately 20% of Sjögren’s syndrome cases (1), although the exact figure is controversial and studies differ in their diagnostic criteria, population selection, referral bias, and special interest (3).

Cognitive symptoms of Sjögren’s syndrome may include difficulties with attention, working memory, memory, and executive functions. Severity can range from very mild to the level of dementia (1). The pathogenesis of neurological Sjögren’s syndrome is not well defined. Evidence has pointed towards an immunologically mediated mechanism, small vessel vasculitis (inflammation), or an interaction of the two. The neurological symptoms of Sjögren’s syndrome can resemble those of multiple sclerosis. However, the presence of peripheral nervous system dysfunction, such as neuropathy and carpel tunnel syndrome, in addition to central nervous system complications (impacting the brain and the spinal cord), sets Sjögren’s syndrome apart from multiple sclerosis (3). Most forms of treatment of Sjögren’s syndrome aim at symptom relief, such as treating dry eyes and mouth. Corticosteroids and immunosuppressive medications may be used to treat more aggressive progressions of Sjögren’s syndrome, and dementia due to Sjögren’s syndrome may be reversed after treatment (3).

By Michelle Chen


  1. Glass, J (2010). In C. L. Armstrong & L. Morrow (Eds.), Handbook of medical neuropsychology (pp. 397-412). New York: Springer.
  2. Binder, L & Campbell, K (2004). Medically unexplained symptoms and neuropsychological assessment. Journal of Clinical and Experimental Neuropsychology26(3), 369-392.  https://www.ncbi.nlm.nih.gov/pubmed/15512927
  3. Tay, S & Mak, A (2017). Diagnosing and attributing neuropsychiatric events to systemic lupus erythematosus: time to untie the Gordian knot?. Rheumatology56(suppl_1), i14-i23.
  4. Benedict, R, Shucard, J, Zivadinov, R, & Shucard, D (2008). Neuropsychological impairment in systemic lupus erythematosus: a comparison with multiple sclerosis. Neuropsychology review18(2), 149-166.
  5. Soliotis, F, Mavragani, C, & Moutsopoulos, H (2004). Central nervous system involvement in Sjögren’s syndrome. Annals of the rheumatic diseases63(6), 616-620.