Stratifying cognitive dysfunction in SLE
Research type
Research Study
Full title
Stratifying cognitive dysfunction in systemic lupus erythematosus and its associated factors: a pilot study
IRAS ID
270243
Contact name
Ben Parker
Contact email
Sponsor organisation
University of Manchester
Duration of Study in the UK
1 years, 1 months, 2 days
Research summary
Research Summary
Problems with memory, attention and planning, also known as cognitive functions, are often reported by patients with systemic lupus erythematosus (SLE), commonly referred to as “brain fog”. Some studies have found that SLE patients perform similarly to healthy volunteers on cognitive tasks until they become fatigued leading to dysfunction. Recent brain imaging studies have supported this by showing that SLE patients’ brains are working harder to maintain a similar level of cognitive function to health volunteers. This suggests they may become fatigued quicker and develop “brain fog”. These problems significantly affect quality of life, however, there are limited treatment options at present.
This study will recruit 100 SLE patients from Manchester University NHS Foundation Trust (MFT) rheumatology clinics and collaborating clinics in the region. Each participant will have a one-off visit during which blood samples will be taken and questionnaires/assessments administered to look at factors such as depression, anxiety, sleep disturbance, pain, and fatigue. Participants will then be asked about their cognitive function and asked to play simple computer games that test their cognitive function. These games have been designed to immediately identify if the participant has cognitive dysfunction, as per our research definition. If they do their study visit will end; if not they will repeat some aspects of the study. The visit will last between 2-2 ½ hours and should identify 4 groups: those that were immediately impaired (severe cognitive dysfunction), those that were impaired only after being fatigued (mild cognitive dysfunction), those that self-reported cognitive dysfunction but performed within normal limits and those with no cognitive dysfunction. We will then analyse the groups and look at differences between the groups on all the measures that we collect. The aim of this study is to confirm these groups exist and begin to understand contributing factors. The groups can then be used to design a future clinical trial to treat cognitive dysfunction in SLE.
This study is being funded by a grant from LUPUS-UK and NIHR Manchester BRC.
Summary of Results
Problems with memory, attention, planning, also known as cognitive dysfunction, significantly affect people with lupus. The number of patients self-reporting cognitive dysfunction is often higher than those found to have cognitive dysfunction after objective testing. Our previous work found differences in how the brain works in those with lupus compared to people without health conditions. It appeared that the brains of those with lupus had to work harder to maintain the same level of cognitive functioning compared to people without a chronic health condition. This suggests that while lupus patients may manage to maintain adequate cognitive functioning during tasks like objective cognitive testing, the demands of daily life might lead to quicker cognitive fatigue. This fatigue could explain why many lupus patients report cognitive difficulties and experience "brain fog" even in the absence of objective cognitive dysfunction
Our study aimed to examine objective and self-reported cognitive dysfunction as well as cognitive fatigue in people with lupus. We designed a new system to test objective cognitive dysfunction before and after cognitive fatigue. This system aimed to place people into one of six groups based on their level of objective cognitive dysfunction pre and post cognitive fatigue and self-reported cognitive dysfunction.
The aims of the study were to test whether this new system would work and to look at differences between the six groups in terms of participant clinical, demographic and psychiatric characteristics.
Participants had one or two study visits. At these visits, clinical, demographic and psychiatric data was collected. Patients were asked to complete questionnaires examining, cognitive function, pain, fatigue, depression/anxiety, health-related quality of life and sleep quality. They also completed three online cognitive tests that examined attention, visual-spatial skills and new learning (stage 1). Participant performance on the three tasks were assessed during the study visit and categorised as impaired or not. For participants that did not show cognitive impairment, the tasks were repeated a second time (stage 2) during the same study visit.
We are still analysing all the results but what we have found so far is summarised below.
101 lupus patients were recruited to the study. Unfortunately, only 56 completed the study. The primary reason for this was participants lost to follow-up during the COVID-19 pandemic. There were no differences in characteristics between those that completed the study and those that did not.
The 56 participants had the characteristics that you would expect from a group of patients with lupus recruited from a Manchester, UK clinic. Based on our system, the split of the 56 participants was as follows:
• Group 1 (self-reported and objective cognitive dysfunction at stage 1): 27
• Group 2 (self-reported and objective cognitive dysfunction at stage 2, post fatigue): 2
• Group 3 (self-reported cognitive dysfunction): 12
• Group 4 (objective cognitive dysfunction at stage 1): 9
• Group 5 (objective cognitive dysfunction at stage 2, post fatigue): 1
• Group 6 (no self-reported or objective cognitive dysfunction): 3Participants that registered as having objective cognitive dysfunction were mainly affected by the attention task. Factors that appeared to be associated with poorer cognitive performance were age, disease duration, depression, cognitive fatigue and self-reported cognitive dysfunction.
Due to the low numbers in some groups our subsequent analyses focussed mainly on group 1 versus group 3. This comparison was decided as it would give us the clearest understanding of any differences between those with objective cognitive dysfunction and those with only self-reported cognitive dysfunction. Interestingly, there were no differences in demographics, lupus disease factors or patient reported outcomes (e.g. depression, pain, fatigue).
Our system of grouping participants based on the new cognitive tests was successful and we can now look at investigating why some patients develop objective cognitive dysfunction.REC name
London - Fulham Research Ethics Committee
REC reference
19/LO/1845
Date of REC Opinion
10 Dec 2019
REC opinion
Further Information Favourable Opinion