Neurocognitive improvements after best-practice intervention for chronic fatigue syndrome (Cvejic)

[Dolphin]

Neurocognitive improvements after best-practice intervention for chronic fatigue syndrome: Preliminary evidence of divergence between objective indices and subjective perceptions.

Cvejic E1, Lloyd AR2, Vollmer-Conna U3.

Compr Psychiatry. 2016 Apr;66:166-75. doi: 10.1016/j.comppsych.2016.02.002. Epub 2016 Feb 9.


Abstract
BACKGROUND:
Neurocognitive difficulties are commonly reported by patients suffering from chronic fatigue syndrome (CFS). Moderate improvements from 'best practice' therapy are promising, but to date reported efficacy is based entirely on subjective measures. This is problematic, given the well-documented divergence between subjective perceptions and actual neurocognitive performance, including in this patient group.

MATERIAL AND METHODS:
Subjective and objective measures of neurocognitive performance were obtained from 25 patients with well-characterized CFS before and after the completion of a 12-week graded-activity program incorporating a cognitive training component. Additionally, self-reported symptoms, cardiac autonomic activity (a relevant biomarker of stress responsivity), and their relation to neurocognitive improvements were examined.

RESULTS:
Substantive post-intervention improvements in subjective (p=0.006) and objective (including faster responses speeds and greater accuracy, p's<0.001) neurocognitive performance were documented. Participants also demonstrated reduced autonomic reactivity to the cognitive challenge at follow-up (p's≤0.01). These improvements were accompanied by improvements in symptom ratings (p's≤0.01). However, subjective ratings of neurocognitive difficulties, and CFS-related symptoms were not linked to objective performance improvements.

CONCLUSIONS:
These initial data provide the first evidence of objective neurocognitive performance improvements accompanied by a significant reduction in responsiveness in stress-related neural pathways consequent to cognitive-behavioral/graded exercise therapy programs. These findings provide support for the effectiveness of such programs in remediating clinical status. These promising findings warrant further investigation, including replication in a larger sample utilizing more controlled study designs.

Copyright © 2016 Elsevier Inc. All rights reserved.

PMID:
26995250
[PubMed - in process]

 

[Dolphin]

There is no control group in this study. This leaves the big question about whether these improvements can be put down to the intervention or instead whether they could be explained by training effects (being more familiar with the tests), the passage of time, et cetera.

This is what the authors say on this for what it is worth.

However, the mechanisms underlying performance improvements remain to be established. It may be argued that the observed performance improvements may simply be due to the use of a repeated measures design, with previous exposure, familiarity, and reduced anxiety to neurocognitive tasks eliciting quicker responses during follow-up assessment. However, given that the average period between assessments was 11 weeks, combined with the use of parallel forms of computerized tasks, this is unlikely. Moreover, a previous study utilizing a test–retest paradigm over two weeks with a comparable version of the Stroop task in healthy volunteers [60] showed an average RT improvement of only 35 ms. In comparison, a substantially greater improvement in RT (~400 ms) without loss of accuracy was observed here post-intervention, indicating that something more than a repetition effect likely underlies performance improvements.

4.1. Limitations

The use of a within-subject design without an appropriate comparison group limits the findings of this study.

 

[Bob]

25 fatigued patients who undertook 12 weeks of cognitive training improved their cognitive scores in cognitive tests after the training. And no control group. Now that's what I call a useful and rigorous research program putting public money to best use.

 

[Snowdrop]

Yet another good reason for those of us with more than just fatigue to call our illness something other than cfs.

 

[barbc56]

What is involved with best standard practice? CBT/GET?

 

[Dolphin]

What is involved with best standard practice? CBT/GET?

Yes.

2.3. Intervention

The multi-disciplinary outpatient treatment program for CFS [42] has been established within a clinical academic framework combining interventions tailored to individual patients by providing CBT along with physical remediation and cognitive retraining. The program is delivered by one of two clinical psychologists and one of two exercise physiologists across six to eight individual one-hour sessions. These sessions incorporate an integrated modular treatment approach that has educational components, addressing difficulties with physical activity and exercise regulation (using a GET approach), sleep–wake cycle, neurocognitive functioning, and mood. Importantly, analogous to GET, patients are asked to pace and then gradually escalate their cognitive tasks (e.g. reading, responding to emails) by completing one or more timed sessions of such structured mental activity every day. When a tolerated routine was in place, the time spent on each activity and the level of intensity was progressively increased. The aim of this program is to assist patients with re-conditioning, both physically and cognitively, toward normal everyday functioning.

 

[duncan]

Only 12 weeks before repeating the same tests?

12 weeks is nothing. Watch an episode of Game of Thrones. Will you recall elements of that episode 12 weeks later as you watch a repeat of it?

This is not enough time. Subjects will remember. The relatively recent exposure will elevate their scores. Many of these metrics are based on prompting and recall.

I am surprised a neurocognitive testing expert has not spoken up yet.

 

[Hutan]

There is no control group in this study. This leaves the big question about whether these improvements can be put down to the intervention or instead whether they could be explained by training effects (being more familiar with the tests), the passage of time, et cetera.

Exactly.

Moreover, a previous study utilizing a test–retest paradigm over two weeks with a comparable version of the Stroop task in healthy volunteers [60] showed an average RT improvement of only 35 ms. In comparison, a substantially greater improvement in RT (~400 ms) without loss of accuracy was observed here post-intervention, indicating that something more than a repetition effect likely underlies performance improvements.

The CFS patients had 11 or 12 weeks of cognitive training between the two assessments. The healthy volunteers did a different (although reportedly comparable) cognitive task in a test-retest scenario (ie presumably no training in between the two tests) with two weeks between the test and re-test. So, are we surprised the CFS patients' performance improved rather more than that of the healthy volunteers?

The stupidity of these studies and their conclusions continues to amaze me.

 

[Woolie]

There is no control group in this study.

Yea, first thing I noticed. WTF? How does this stuff get published?

 

[barbc56]

Yes

That's what I was afraid of. Grrrrrrrr!

Does this apply to the states? Sorry, rather foggy and can't find this info. From the WHO?

 

[barbc56]

Okay, found this for the states. It's the CDC me/cfs under management but I'm not sure if that is considered best practice. While cbt and get are mentioned, there are also other things.

http://www.cdc.gov/cfs/management/index.html

There is a PDF but I can't access it nor post the url from my phone. It's titled toolkit for providers.

 

[alex3619]

This should be considered a pilot study. In order to evaluate it we need at least two, not one, control groups. We need a no intervention group, and we need a group receiving only the cognitive training. I have not read the full study.

The use of objective measures is commendable ... but they must expect us to be skeptical given prior failures, including major methodological failures, in this kind of research.

This caveat puts a damper on the whole thing as well:

However, subjective ratings of neurocognitive difficulties, and CFS-related symptoms were not linked to objective performance improvements.

I have major memory deficits right now. Yet when tested with a very simple memory test for dementia I aced it. If the neurocognitive testing did not examine the kinds of deficits expected in ME or CFS then its largely irrelevant. Nobody has yet put together a validated and public neurocognitive battery focusing on the typical neurological deficits found in ME or CFS. I am aware this kind of testing can be done privately, but this is not common, and we need some data on how to conduct this kind of testing, which might come from one or more of the big data studies currently underway or in planning.

Another confound would be duration and severity of illness. Most of these kinds of intervention studies are for moderate term patients with mild to moderate severity. Long term patients are usually ignored, and the same for severe patients.

I am also concerned that there is a presumption that daily neurocognitive tasks like what they describe are presumed to have stable results over time. I have been doing those kinds of things for decades. I still have long periods where my cognition sucks, and other times when it is not so bad (though not recently).

There is also an issue of short term neurocognitive performance after rest versus after exertion and delayed problems after exertion.

I also want to know about effect size, not just p values.

 

[Justin30]

When are they really gonna start selecting people that represent what ME.

CFS shoulf be taken away from the connection of ME immediately so science can actually start making strides.

 

[alex3619]

When are they really gonna start selecting people that represent what ME.

CFS shoulf be taken away from the connection of ME immediately so science can actually start making strides.

I have read the abstract a few times but still have no clue over cohort selection. It is indeed critical to know this when trying to interpret the study. The use of "CFS" rather than "ME/CFS" or even "CFS/ME" suggests that cohort selection was especially poor. What does "well-characterized CFS" actually mean?

 

[Justin30]

I have read the abstract a few times but still have no clue over cohort selection. It is indeed critical to know this when trying to interpret the study. The use of "CFS" rather than "ME/CFS" or even "CFS/ME" suggests that cohort selection was especially poor. What does "well-characterized CFS" actually mean?

Maybe people that are sleepy after they work a full days work, take care of there kids and Participate in a normal life.

 

[Art Vandelay]

It's by Andrew Lloyd. Say no more.

 

[Valentijn]

Full text from sci-hub: http://www.sciencedirect.com.sci-hub.cc/science/article/pii/S0010440X15302492

They cite to Fukuda Criteria, but have offered up a very strange interpretation of it:

Chronic fatigue syndrome (CFS) is a complex and debilitating disorder characterised by six or more consecutive months of medically-unexplained fatigue and multiple constitutional and neuropsychiatric symptoms [1].

9 of the 25 patients were on antidepressants, and had been for a while, which is a bit unusual since a lot of ME patients don't tolerate them. People taking meds for autonomic symptoms were excluded, but SNRIs were classified only as antidepressants, despite the impact norepinephrine has upon the autonomic nervous system.

Length of illness was as low as 24 weeks (6 months) in some patients, meaning they were barely ill long enough to be diagnosed. Though average was about 5 years. Some were drinking up to 6 units of alcohol per week, which is pretty remarkable in a disease where alcohol intolerance is a nearly universal symptom. Some patients doing up to 15 hours of moderate intensity exercise per week (3.8 hours on average) is also suspicious in a disease defined by a pathological intolerance of exertion.

There's no indication that they adjusted for making multiple comparisons in the before-and-after measurements. Though they did adjust for multiple comparisons in comparing the end results to each other to see which outcomes correlated with each other. So it's unlikely there was much (if any) actual statistical significance.

 

[A.B.]

Short illness duration (in some patients), permissive Fukuda criteria imply that regression to the mean could be particularly prominent in this sample. So the lack of a control group is particularly problematic.

 

[sarah darwins]

Is it me or is junk science not what it used to be? They don't even seem to be pretending properly any more.

 

[A.B.]

There is a positive aspect to this study. It acknowledges objective neurocognitive deficits, and touches the issue of discrepancies between subjective and objective measures. Which suggests that at least some of the people promoting psychosomatic explanations no longer feel that these issues can continue to be ignored.