Cognitive assessment in ME/CFS: a cognitive substudy of the multi-site clinical assessment of ME/CFS (MCAM), 2024, Lange, Unger +

https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1460157/full

Cognitive assessment in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a cognitive substudy of the multi-site clinical assessment of ME/CFS (MCAM)

Introduction: Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) experience cognitive problems with attention, information processing speed, working memory, learning efficiency, and executive function. Commonly, patients report worsening of cognitive symptoms over time after physical and/or cognitive challenges. To determine, monitor, and manage longitudinal decrements in cognitive function after such exposures, it is important to be able to screen for cognitive dysfunction and changes over time in clinic and also remotely at home. The primary objectives of this paper were: (1) to determine whether a brief computerized cognitive screening battery will detect differences in cognitive function between ME/CFS and Healthy Controls (HC), (2) to monitor the impact of a full-day study visit on cognitive function over time, and (3) to evaluate the impact of exercise testing on cognitive dysfunction.

Methods: This cognitive sub-study was conducted between 2013 and 2019 across seven U.S. ME/CFS clinics as part of the Multi-Site Clinical Assessment of ME/CFS (MCAM) study. The analysis included 426 participants (261 ME/CFS and 165 HC), who completed cognitive assessments including a computerized CogState Brief Screening Battery (CBSB) administered across five timepoints (T0-T4) at the start of and following a full day in-clinic visit that included exercise testing for a subset of participants (182 ME/CFS and 160 HC). Exercise testing consisted of ramped cycle ergometry to volitional exhaustion. The primary outcomes are performance accuracy and latency (performance speed) on the computerized CBSB administered online in clinic (T0 and T1) and at home (T2-T4).

Results: No difference was found in performance accuracy between ME/CFS and HCs whereas information processing speed was significantly slower for ME/CFS at most timepoints with Cohen’s d effect sizes ranging from 0.3–0.5 (p < 0.01). The cognitive decline over time on all CBSB tasks was similar for patients with ME/CFS independent of whether exercise testing was included in the clinic visit.

Conclusion: The challenges of a clinic visit (including cognitive testing) can lead to further cognitive deficits. A single short session of intense exercise does not further reduce speed of performance on any CBSB tasks.

 

So accuracy showed no difference but performance speed does. Exercise had no further impact on cognitive functioning.

Here's quote from the discussion section that summarizes the findings:

 

A description of the tasks is available in the supplementary material. Except for the maze (GML) they seem rather easy tasks focusing on detection and memory.

CogState Brief Screening Battery (CBSB)

Detection Task (DET): Task stimuli are images of playing cards showing either red or black jokers. The DET measures simple reaction time (RT) defined as the time it takes to press a “Yes” button as soon as a playing card in the center of the screen flips over.

Identification Task (IDN): Task stimuli are again images of playing cards showing either red or black jokers. The IDN task measures attention by employing a choice reaction time paradigm. Participants have to indicate whether or not a playing card is red as quickly as possible by pressing “Yes” if the playing card is red and “No” if it is black.

One Card Learning Task (OCL): Task stimuli are again playing cards, but this time without jokers. The OCL task measures recognition memory by employing a pattern separation paradigm. Participants press the “Yes” or “No” button to indicate whether or not they recognize having seen the currently displayed card at any time previously in the deck.

1-Back Working Memory Task (ONB): Task stimuli again are playing cards without jokers. The ONB measure working memory by employing the n-back paradigm. Again, participants press a “Yes” or “No” button as quickly as possible to indicate whether or not the current card presented is the same as the card just previously presented (one back) or not.

2-Back Working Memory Task (TWOB): Task stimuli again are playing cards without jokers. The TWOB measures working memory also by employing the n-back paradigm. In the TWOB task, participants press the “Yes” or “No” button as quickly as possible to indicate whether or not the current card presented is the same as the card shown two cards previously (two back). The first response is always “No” because no comparison card has been presented yet.

Groton Maze Learning Task (GML): The GML assesses problem solving, reasoning, and efficient learning under time pressure using a maze learning paradigm. A 28-step pathway is hidden among 100 possible locations in a 10 × 10 grid of tiles on the screen. Each box represents move locations, and the grid refers to the box array (i.e., 10 × 10). Participants are required to find a hidden pathway guided by four search rules. These rules are: 1) do not move diagonally, 2) do not move more than one box (i.e., do not jump), 3) do not move back on the pathway, and 4) return to the last correct location after an error. Feedback is given with visual and auditory cues (green check marks and red crosses as well as beeps) to indicate whether the selected box is correct or incorrect. The last correct location, flashes with a green check when two errors are made in succession (failing to return errors). At each step only the most recently selected box is shown. There are 20 well-matched alternate pathways available. The software records each move as either an error or as a correct move. The primary outcomes are the total number of errors made in attempting to learn the same hidden pathway on five consecutive trials at a single session (GML-TER) and the total number of correct moves made per second (GML-MPS).​

 

Traditional Neuropsychological Tests
The following two traditional neuropsychological tests were used and took about 10 minutes to be completed.

Test of Premorbid Functioning (TOPF (Pearson, 2009): The TOPF requires participants to read a list of 70 phonetically irregular words. The ability to successfully pronounce irregularly spelled words is relatively resistant to neurological injury and a sensitive marker of intellectual attainment (Holdnack, et al., 2013). Participants must read and pronounce a list of words printed in two columns on the front and back of a card. The TOPF was scored according to procedures outlined in the manual (Pearson, 2009). The best possible raw score for the TOPF is 70 and a derived age-corrected standard score (SS) can be used to predict the expected premorbid WAIS-IV Full Scale IQ score. The TOPF was only administered at T0.

The Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) Digit Span Forward and Backward tasks (DSF & DSB) (Wechsler, 2008): These two tasks were verbally administered. The DSF is often described as a test of simple auditory attention while the DSB is a test of simple auditory working memory. In the DSF test, participants are asked to repeat digits, the length of the digit sequence is increased across trials until there is a failure across two consecutive trials of a particular length. In the DSB test, participants are asked to repeat digits backwards across trials until there is a failure across two consecutive trials of a particular length. Raw scores range from 0 to 16 on both tasks and can be converted to age-corrected Standard Scores (SS). DSF and DSB were only administered at T0 and T1. ​

 

This is more important than we might think.

it underlines the issue is exhaustion and load (same category - more load = more exhaustion) and not ‘ability’ or importantly ‘capacity’ in the sense of DOLS because if not already antagonised health-wise or wsiting fir right point we can both think very clearly having taken in info to make decisions and communicate them with adjustments appropriate to our disability. Yet if someone rushes us having decided to shine lights to desensitise us to photophobia or noise or whatever then that’s like the old cliche of interrupting a stroke patient fir speaking slowly or not pronouncing something right and assuming they also can no longer think.

I can’t help but being very aware and pointing out to non-Uk people that in the UK it has always been a strange historical point that dementia patients including Alzheimer’s got screwed on care and had to sell their home ending up with care for many years where other health illnesses it was different

alzheimer I mention specifically because the rest are ‘old age’ and that was the justification (pay for your own old age care if you’ve savings) but Alzheimer’s has early-onset variations.

 

"A new scientific paper shows impaired cognitive functioning in ME/CFS. While this will not be a surprise to anyone with the condition, the study helps us understand the nature and extent of the problem. You can find the open access full paper here: https://pmc.ncbi.nlm.nih.gov/articles/PMC11565701/

Jarred Younger"

https://www.youtube.com/watch?v=GhV6oGg-JXY

 

This is a step in the right direction, but I worry about the abstract/summary; many clinicians will jump to results and conclusions and only see

I've taken five tests of this type over the last several years, and I've found them generally off-mark.

They need to compare premorbid scores of pwME to current scores.

They need better tests. Cognitive decline is substantive in many pwME, and those declines can be global. They also seem to dovetail with other red flags for brain involvement like OI and POTS and balance issues. These tests should also assess the sifting and sorting and executing of multiple cognitive demands simultaneously like the real world requires. And what about domains such as planning and creativity and inference abilities?

Moreover, these tests don't seem to consider the pedestrian capability to focus and perform better than usual for relatively short bursts, but a capability that cannot be sustained. Give five different but similar tests over five days in a row and see where the values fall.

There are some good names on this list of authors, but some other ones that cause me concern.

ETA: Geez, do even I have any idea how many times I had to edit this short narrative that years ago would have just effortlessly flowed?? And it's still muddled! Test that figgen deficit and assess it accurately. Please.

 

Prior to my appointment with researchers in The Netherlands I was asked to do a N 2(pictures) back N 3 back test over a 3 week period, on-line, at home, on good moments and bad moments.
Reaction time and memory accuracy were tested. The differences in good or bad moments were pretty obvious. In 3 back misstakes doubled and reaction time was up 50% on bad moments.
Had I only done a few tests elsewhere, with travel time, the difference would not have been so clear. (effect of adrenaline?)

Had I even tried after my appointment, the outcome would have been disastrous. I had to travel during covid-lockdown, 6 hours (twice) of travel time on public transport. In the middle of the day a tilt-table-test.
Up at 4.00 and in bed at 22.00, I lost my marbles for 48 hours, (working memory?) (@MelbME that doesn't mean I'm bonkers), PEM lasted a month. I was given a standing test, 60+ and just 40% VO2max on CPET. Stepping away on 90 degrees standing still afterwards (-25%CBF). A disaster in the making.

To all people doing tilt-table testing, professionals and patients; Please end the test in supine position. The test takes away your coping mechanisms.
Ending supine means you get your coping mechanisms back and restores the CBF-drop at least a little.
@duncan this post took me over 2 hours, on and off.

edited for clarity

 

Typical of CDC's MCAM studies

 

Does it say how long after exercise the cognitive testing was done?

Because if I overexert myself, I get a bout of what feels like adrenaline and my cognitive function doesn’t decline until the adrenaline (or whatever) wears off and PEM hits the next day.

Edit: Hmm it seems they had a test after 48hrs

Well a lack of difference there is certainly intriguing, but also worth keeping in mind these people had the functional capacity to spend an entire day at a clinic, which leaves out a specific portion of ME pateints.