Cognition and Chronic Fatigue Syndrome (ME/CFS): Key Findings and Seminal Papers

This is consistent with our previous findings of significant fluctuation in sustained attention and concentration in CFS [5] and point to an ongoing struggle to keep attention focused on the task at hand. Vollmer-Conna

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[fright] [/fright]This paper attempts to identify seminal papers regarding cognition or the ability to think well in chronic fatigue syndrome (ME/CFS). It covers what researcher studies tell us about cognitive problems in ME/CFS; what they are, how serious they are and what might be causing them.

Cognitive Issues

Many people with ME/CFS complain that they aren't able to think or speak as well as before they became ill. Just how cognitively challenged people with ME/CFS are is a bit controversial but over time a pretty clear consensus has emerged regarding the cognitive challenges the group as a whole faces.

It’s important to remember that these findings reflect studies looking at the ME/CFS population as a whole, and might not reflect any one individual's experiences.

Dr. Lange highlighted some of the common problems people with ME/CFS have in a 2010 Solve ME/CFS Initiative Webinar

• Needing to read the same paragraph over and over again to understand it
• Speaking sentences that defy the rules of grammar and logic
• Agonizing decision-making processes
• Heretofore easy to understand conversations taking on an almost algebraic difficulty

The Core Problem

The finding from the CDC study below that information processing speed was significantly worsened in ME/CFS highlighted the chief, objective cognitive impairment in ME/CFS.

Neuropsychological performance in persons with chronic fatigue syndrome: results from a population-based study. Psychosom Med. 2008 Sep;70(7):829-36. doi: 10.1097/PSY.0b013e31817b9793. Epub 2008 Jul 7. Majer M1, Welberg LA, Capuron L, Miller AH, Pagnoni G, Reeves WC.

This study demonstrated that information processing speed and working memory are significantly worsened in chronic fatigue syndrome and those deficits are not related to depression or other mood disorders.

While individual patients may have other problems a recent review reported that information processing is the core cognitive problem in ME/CFS. (Dr. Gudrun Lange - who has tested many people with ME/CFS also highlights low working memory and reduced executive planning.)

Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence. Curr Rheumatol Rep. 2016 May;18(5):24. doi: 10.1007/s11926-016-0577-9. Cvejic E1, Birch RC1, Vollmer-Conna U2.

Information processing speed is not as simple as it sounds. Information processing speed refers to a complex set of cognitive processes that allow one to input incoming information, understand and store it, and then respond to it.

It's usually assessed using simple tasks but studies indicate that the speed with which people with ME/CFS are able to process, understand and respond to information decreases substantially when they are faced with more complex tasks.

Studies do not suggest that people with ME/CFS are less smart than before, or that they make more mistakes than before or that their memory, believe it or not, is worse than before. Once they get the information into their brains it sticks. Given their issues with slowed information processing the problem is getting information in there in the first place.

Mental Fatigue

Another issue involves mental fatigue. Many people with chronic fatigue syndrome report being mentally fatigued and/or becoming easily fatigued after mental tasks.

A 2008 CDC study finding that ME/CFS patients with more mental fatigue were more impaired cognitively indicated the problem of mental fatigue was real and had significant consequences.

Cognitive dysfunction relates to subjective report of mental fatigue in patients with chronic fatigue syndrome. Neuropsychopharmacology. 2006 Aug;31(8):1777-84. Epub 2006 Jan 4. Capuron L1, Welberg L, Heim C, Wagner D, Solomon L, Papanicolaou DA, Craddock RC, Miller AH, Reeves WC.

[fleft] [/fleft]Some have supposed that anxiety or depression could be responsible for the cognitive issues present in ME/CFS but a CDC study two years later indicated the cognitive issues in ME/CFS were a unique feature of the disease itself. '

Neuropsychological performance in persons with chronic fatigue syndrome: results from a population-based study. Psychosom Med. 2008 Sep;70(7):829-36. doi: 10.1097/PSY.0b013e31817b9793. Epub 2008 Jul 7. Majer M1, Welberg LA, Capuron L, Miller AH, Pagnoni G, Reeves WC.

Another study directly comparing the cognitive issues in ME/CFS, depression and healthy controls found the cognitive complaints in people with depression were indeed strongly associated with the degree of their depression and their subjective fatigue. This was not true in ME/CFS, however; the correlation between cognitive issues and depression was much weaker and did not apply with regards to fatigue.

The study also indicated effort was not the issue with ME/CFS either; the patients in the study displayed good effort.

Cognitive deficits in patients with chronic fatigue syndrome compared to those with major depressive disorder and healthy controls. Clin Neurol Neurosurg. 2011 May;113(4):295-302. Epub 2011 Jan 20.
Constant EL1, Adam S, Gillain B, Lambert M, Masquelier E, Seron X.

Inefficient Brains

Several studies suggest that an inefficient use of brain resources may be causing problems in ME/CFS. When asked to do a task people with ME/CFS tend to use more parts of their brains to carry it out and/or have trouble staying focused on the task itself.

Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory. Neuroimage. 2005 Jun;26(2):513-24. Epub 2005 Apr 7. Lange G1, Steffener J, Cook DB, Bly BM, Christodoulou C, Liu WC, Deluca J, Natelson BH.

This 2005 study featuring Dr. Lange and Dr. Natelson, found that people with chronic fatigue syndrome can process sounds as accurately as healthy controls but have to use more parts of their brains to do so. This suggests they have to work harder to understand sounds, resulting in greater effort and mental fatigue.

Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome. Neuroimage Clin. 2015 Sep 10;9:355-68. doi: 10.1016/j.nicl.2015.09.001. eCollection 2015. Mizuno K1, Tanaka M2, Tanabe HC3, Joudoi T4, Kawatani J4, Shigihara Y2, Tomoda A5, Miike T6, Imai-Matsumura K7, Sadato N8, Watanabe Y9.

A similar pattern was seen in children with ME/CFS. When asked to pay attention simultaneously to two different tasks (picking out the vowels in a story and understanding it) children with ME/CFS had to activate more areas in their front parts of their brain to do this.

The authors stated the children had to engage in a "massive mental effort" to overcome their poorer performance at the dual task. Multi-tasking, therefore, suffers in ME/CFS and is inherently more fatiguing than for healthy people.

Dan Cook's 2007 study demonstrated a similar pattern when it found that adults with chronic fatigue syndrome had to activate more areas of the brain in order to complete a cognitive task. The authors proposed the findings might explain the mental fatigue present in ME/CFS.

Functional neuroimaging correlates of mental fatigue induced by cognition among chronic fatigue syndrome patients and controls. Cook DB1, O'Connor PJ, Lange G, Steffener J. Neuroimage. 2007 May 15;36(1):108-22. Epub 2007 Mar 3.

The degree of activity in any part of our brain is a function of the blood flowing to it; the more blood that flows to a region the more active it is. A PET scan study confirmed what other brain imaging studies suggested; that when given a task, instead of the blood flowing specifically to the region of the brain that carries out that task, the blood flows in ME/CFS patients flow to other regions as well.

Cause

Many things can cause slowed information processing. Wear and tear in the pathways that connect different parts of the brain together (white matter) are often involved. The fact that slowed information processing is a function of aging is intriguing given the telomere evidence that people with ME/CFS may be aging more rapidly than normal.

The association of vascular problems in diabetes with slowed information processing provides another possibility for ME/CFS. The blood vessels or cardiovascular connection to cognitive issues was highlighted when researchers were able to reverse the cognitive problems in ME/CFS/POTS patients by giving them a drug which increased the blood flows to their brains. Using this drug POTS patients were asymptomatic and able to think as clearly as the healthy controls during a Tilt table test.

In her 2012 webinar, however, Dr. Gudrun Lange didn't feel that low blood flows, gray or white matter problems or lactic accumulations necessarily explained the cognitive issues.

She believes that issues across the brain that also effect sleep and alertness, that cause increased ‘arousal’ (i.e., fight or flight), increased pain and body sensations, vertigo, autonomic nervous system problems, memory, the stress response, and even immune problems probably all contribute to the cognitive problems in ME/CFS; i.e. the cognitive problems are simply a consequence of a multi-systemic problem.

Vagus Nerve and Prefrontal Cortex Involvement

Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome.PLoS One. 2012;7(11):e49518. doi: 10.1371/journal.pone.0049518. Epub 2012 Nov 14. Beaumont A1, Burton AR, Lemon J, Bennett BK, Lloyd A, Vollmer-Conna U.

Problems with the prefrontal cortex and vagus nerve provide another possibility. The study found that heart rate variability - which is under the control of the vagus nerve - declined during the test in the ME/CFS patients but not in the healthy controls.

Furthermore, the heart rate - also under control of the vagus nerve - returned to normal levels quickly after the test in the healthy controls but not in the people with ME/CFS. The author proposed that damage to the prefrontal cortex of the brain prevented it from properly regulating the autonomic nervous system.

Neither somatic symptoms, psychological distress, functional impairment, or subjective ratings of energy, fatigue or effort on the other hand were associated with reduced cognition.

Conclusions

The cognitive problems in ME/CFS are real. The main cognitive issue is something called slowed information processing - which refers to difficulty taking in information, processing it and responding to it. Slowed information processing could show up in difficulty following conversations, understanding blocks of text, responding to situations, etc.

People with ME/CFS tend not to have memory problems - when something is embedded in their memory it tends to stick - the problem is getting it into their memory banks.

Mental fatigue is common and may be associated with a brain that allocates it's resources inefficiently. People with ME/CFS tend to use more parts of their brain than normal to carry out cognitive tasks - a process that is inherently fatiguing.

What's causing the cognitive issues is unclear, but could involve blood vessels problems and frayed connections between different parts of the the brain.

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• Check out more cognitive resources in Health Rising's Cognition section including Dr. Lapp on ways to treat the cognitive problems present.