Fatigue and cognitive dysfunction (“brain fog”) in rheumatic diseases can be debilitating, impacting daily activities and quality of life more than joint pain. It’s essential to acknowledge these pervasive symptoms and provide more support for patients to manage them effectively.
What causes fatigue in rheumatic diseases?
Dr. Ayman Askari – Rheumatologist: One cause would be the activity of disease, which means the presence of active inflammation. Another ignored cause of fatigue in my view is the lack of sleep. Frequently we do not know the cause of fatigue and the management is not easy, however, it is important from a physician point of view to rule out other missed causes of fatigue, such as endocrine causes, anaemias and nutrition.
Dr. Daniel Whibley – Assistant Professor in the Department of Physical Medicine and Rehabilitation at the University of Michigan:
- Inflammation/pro-inflammatory cytokines (as stated by Dr. Askari) – Supporting this, Druce et al. have shown that patients receiving anti-TNF therapies experience clinically important improvements in RA-related fatigue. However, this group has also shown that fatigue can continue to be a problem even when disease remission has been achieved. Presence of depression, and use of antidepressants and steroids were associated with having disease remission but persistent fatigue. A history of stroke and high blood pressure were also associated with higher fatigue. These findings support an argument for multifactorial causes of fatigue.
- Pain (pain can cause fatigue through both physiological and psychological pathways)
- Medication side effects (e.g. steroids, some immunosuppressants)
- Anemia
- Muscle weakness and deconditioning due to reduced physical activity due to pain or joint damage. This can support a ‘vicious circle’ by which every day activities become more tiring
- Depression and anxiety (physical, mental and emotional fatigue!)
- Nutritional deficiencies (e.g., iron, vit D, vit B12)
Poor sleep. Sleep loss can significantly contribute to fatigue and cognitive dysfunction:
- Disrupt circadian rhythms
- Impact on cognitive functions including attention, problem-solving, and decision-making, which can result in mental fatigue
- Cause hormonal imbalances (e.g., stress hormone cortisol, and hormones that regulate energy (e.g., leptin and ghrelin). So, sleep loss can increase stress and lead to an imbalance in hunger-regulating hormones. This can lead to increased fatigue and decreased energy reserves.
- Increase inflammation
- Lead to cardiovascular problems (may be linked to comorbid sleep apnea), physical fatigue and reduced stamina
- Disturbed mood, anxiety, depression and irritability (emotional fatigue)
- Suboptimal cellular repair (sleep disturbances can diminish repair and recovery, leading to physical exhaustion)
What is the impact of fatigue on someone’s quality of life?
Dr. Ayman Askari – Rheumatologist: The impact of fatigue is very negative on the emotional stability , family and the quality of life, particularly if you are a working person. It interferes with your daily activities and sometimes it will lead to depression. Post-viral fatigue, as we saw in Covid era, has caused increased incidents of depression and mental illness, and this is well documented.
Cheryl Crow – Occupational Therapist and Person Living With a Rheumatic Disease: After running support groups for five years for people with inflammatory arthritis and engaging with the RA community on social media it’s clear that fatigue is more devastating than pain for many patients. As a patient myself, fatigue is what causes me to say “no” to social and professional opportunities when I want to say “yes.” It makes it harder to engage in my social life, it makes dating harder, parenting harder…everything harder! It robs you of your vitality and the energy to be fully present in your life.
What are some effective treatments for fatigue from your expertise?
Dr. Ayman Askari – Rheumatologist: Treatment of fatigue is a challenge. I believe that supervised exercise with support is probably the correct approach to treat fatigue, and of course ruling other causes and building confidence and rapport with patients. NICE recommends CBT , and GET ( Graded exercise therapy) . I believe in a holistic approach with emphasis on / Mental health is the correct management . I often prescribe magnesium to improve sleep. I use coenzyme q10, vitamin D and vitamin C, B12. I am aware that there are other medications, Amantadine, Guanfacine, Carnitine, D.Ribose, Ginseng that have been used in various studies. This is not supported by the National Health Service and in my country, patients usually self- fund, and success is variable.
Cristina Montoya – Registered Dietitian and Person Living With a Rheumatic Disease: Collaboration with the rheumatologist or family physician to investigate and correct potential nutritional deficiencies contributing to fatigue, such as iron, Vitamin B12, folate, vitamin D, and even vitamin C if a person lives in isolation and relies on food banks to meet their nutritional needs. A recent case study of scurvy in a 65-year-old from Toronto raised the alarm about nutritional deficiencies in individuals with low socio-economic status with limited access to fresh produce. The initial manifestations of hypovitaminosis C are often nonspecific, including fatigue, lethargy, weakness, irritability, and low mood
Dr. Daniel Whibley – Assistant Professor in the Department of Physical Medicine and Rehabilitation at the University of Michigan:
Accordingly, fatigue management may include:
- Managing inflammation
- Optimizing pain control
Improving sleep:
Supporting increasing in physical activity/exercise (Basu’s LIFT trial 3 for inflammatory arthritis – a personalized exercise program can significantly reduce fatigue severity and the impact of fatigue – maintained six months after the intervention)
Addressing psychological health, including using cognitive behavioral approaches (This is not the same as behavioral activation to increase activity, but is based on the theory that active disease can have an impact on mood and symptoms of depression and anxiety, which can mean a person limit their day-to-day activities, which can lead to feelings of fatigue. Fatigue is then exacerbated as psychological factors lead to more and more withdrawal. CB approaches encourage a person to identify their valued activities and, in a graded way, re-engage, to increase vitality as a pathway to reduced fatigue). Basu’s LIFT trial 3 for inflammatory arthritis – a cognitive behavioral approach can significantly reduce fatigue severity and the impact of fatigue – maintained six months after the intervention)
Balancing dietary intake
Treatments for fatigue that I can speak to:
- Personalized Exercise (Basu LIFT trial 3 )
- Energy conservation techniques
- Cognitive Behavioral Approaches
- Treatment of sleep disorders/disturbances (e.g., sleep apnea)
- Treating anemia, depression, anxiety
- Combination of the above
Cheryl Crow – Occupational Therapist and Person Living With a Rheumatic Disease: Comprehensive self-management and psychoeducational programs are recommended to help patients learn tools to prevent and reduce fatigue (citations: 2022 ACR integrative guidelines for RA and the 2023 Fatigue guidelines from EULAR).
If I could recommend only one intervention for people with rheumatic diseases who struggle with fatigue, it would be exercise. In study after study, people who engage in physical activity (specifically cardiovascular exercise) show less fatigue, less pain and stiffness, better sleep and better quality of life. In one study they even showed significant reductions in C reactive protein (citations: The Effect of Exercise on Sleep and Fatigue in Rheumatoid Arthritis: A Randomized Controlled Study (2014), Benefits of exercise in patients with rheumatoid arthritis: a randomized controlled trial of a patient-specific exercise programme (2014) )
Why is there a lack of research around fatigue?
Dr. Ayman Askari – Rheumatologist: It is likely that fatigue is not a life-threatening condition and that is probably why there is an international lack of research on management of fatigue, so it is not like a myocardial infarction of cancer that may end your life, however, it is quite unpleasant to have a life with chronic illness, let alone the impact on family life. I am afraid big pharma, for probably economic reasons, has not invested in this particular condition.
Cheryl Crow – Occupational Therapist and Person Living With a Rheumatic Disease: It appears to me that physicians and researchers are focused more on the objective clinical markers of disease activity (tender joint count, swelling, imaging results, blood counts) than on subjective measures like fatigue. It’s seen as less “real” than pain, even though it can have a more severely adverse effect on quality of life than pain. Additionally, because the little research that exists does show fatigue is multifactorial, it’s harder for researchers to isolate the relationship between a particular intervention and fatigue.
How does your profession/research address fatigue?
Dr. Ayman Askari – Rheumatologist: In my institution as a rheumatologist, we rely on therapists, physical therapy, occupational therapy, hydrotherapy, medical education and ruling other causes of fatigue. A few patients may opt for private coaching and joining groups that may take up modalities such as yoga, mindfulness or invest in holistic therapy and herbal treatment
Cristina Montoya – Registered Dietitian and Person Living With a Rheumatic Disease: I encourage including more foods rich in nutrients essential for energy metabolism, particularly B vitamins. These vitamins can be naturally found in a variety of foods, such as whole grains, legumes, nuts, seeds, eggs, fortified soy products, and dairy products.
Consuming foods rich in prebiotic fiber, such as oats, parsley, onions, garlic, bananas, asparagus, and artichokes, alongside resistant starches, enhances the production of short-chain fatty acids (SCFAs) like butyrate. These SCFAs are critical in maintaining gut integrity, supporting overall digestive health, and promoting a balanced gut microbiome.
Limit consumption of ultra-processed foods as they can disrupt the Omega-3 to Omega-6 ratio by increasing the production of arachidonic acid, a pro-inflammatory molecule.
Promote energy-efficient meal prep strategies: plan ahead, batch cook, use energy-efficient appliances like microwaves, slow cookers, and pressure cookers, pre-cut ingredients, and adopt a cook-once-eat-twice approach. Meal service delivery options like HelloFresh or ModifyHealth can be beneficial, especially for patients on specific diets. However, be mindful that these services often cater to North American or European cuisines and may not be culturally appropriate for all individuals.
Supplements like NAC (N-Acetyl L-Cysteine) are thought to help with mitochondrial dysfunction, which may contribute to fatigue. A study of 74 rheumatoid arthritis patients found that 600 mg of NAC reduced nitric oxide and fasting blood sugar and improved HDL cholesterol (the good cholesterol) but did not really improve disease activity. While NAC may not alleviate fatigue, it could help prevent cardiovascular disease.
It’s important to remind patients that when they consider supplements, they should always consult their healthcare provider to check for risks or drug interactions. Ensure the product has third-party testing certification, comes from a reputable manufacturer, and has clear labeling. If it passes these criteria, try it for three months, and discontinue use if it isn’t effective.
Cheryl Crow – Occupational Therapist and Person Living With a Rheumatic Disease: In my clinical training as an OT, I learned about energy conservation and other fatigue interventions in relation to multiple sclerosis (MS). Fatigue was not even listed as a symptom in my textbook that covered rheumatoid arthritis and similar rheumatic diseases. I have found that the compensatory strategies / workarounds suggested for MS also work for rheumatic diseases, including “energy conservation” tools like pacing yourself, chunking out tasks and delegating. Occupational therapists can help walk you though a day in your life and identify areas where you can conserve energy.
Additionally, as mentioned earlier, occupational therapists can help you come up with a workable exercise or physical activity plan of action, as there is so much evidence that exercise is associated with reduced fatigue in RA and similar conditions. Using myself as an example: I’ve found that it’s important to find a “sweet spot” in between “too much” and “too little” activity. When I am inactive, my fatigue is worse, but if I overdo it, I also get a fatigue flare up. Right now, my “just right” window of exercise tolerance is about 25-30 minutes of moderate intensity low impact cardiovascular exercise and 45 minutes of strength training 2-3 times a week.
A major takeaway from running this project is that there is an extreme lack of research, awareness, information and resources about cognitive dysfunction in rheumatic diseases, which highlights a huge gap not just in research but also for organizations who create resources and for healthcare providers when addressing this symptom to patients.
What causes cognitive dysfunction in rheumatic disease patients?
Cheryl Crow – Occupational Therapist and Person Living With a Rheumatic Disease: There is no one universal cause of cognitive dysfunction in rheumatoid arthritis, the cause is not well understood. However, according to a 2023 article, “Multiple factors have been identified as potential contributors of cognitive impairment in RA patients, encompassing autoimmune and inflammatory components, cardiovascular complications, psychiatric disorders, persistent pain, medication side effects, age, genetic factors, and hormonal fluctuations.”
Why is it important to address cognitive dysfunction in rheumatic disease patients?
Cheryl Crow – Occupational Therapist and Person Living With a Rheumatic Disease: Because it adversely affects quality of life and the ability of individuals to function in their daily lives.
How does cognitive dysfunction adversely affect quality of life and outcomes for patients with rheumatic diseases?
Cheryl Crow – Occupational Therapist and Person Living With a Rheumatic Disease: Similarly to fatigue, cognitive dysfunction can adversely affect quality of life and the ability of patients to work and support themselves. It can also lead to safety concerns – for example, a person with RA may find it difficult to sustain attention to task when driving or caring for children.
How does your profession/research address cognitive dysfunction in rheumatic disease?
Dr. Ayman Askari – Rheumatologist: I look at cognitive dysfunction as part of the chronic pain or central sensitization syndrome, and it is manifested on a daily basis by brain fog. If the patient has severe brain fog, as a result of fibromyalgia secondary to a Rheumatic disorder. There is serious consequential risk . They may well forget their medications or take extra tabs or repeat medication which is dangerous. The activities of daily living will be affected. They may be exposed to falls, driving accidents, injuries , so I would argue that the impact of cognitive dysfunction is very serious and it is not addressed as adequately as it should be.
Cheryl Crow – Occupational Therapist and Person Living With a Rheumatic Disease: Cognitive dysfunction interventions would be helpful for rheumatic disease population but aren’t often even considered due to lack of awareness that this is an issue in this population Simple interventions could include educating the patient about methods to accommodate for “brain fog,” such as assisting the patient in setting up reminders for medications and reminders for other daily activities that might be forgotten. Additional interventions include exercise interventions to improve cognitive function (as mentioned earlier).
