Title: Identifying and treating cognitive impairment in fibromyalgia and chronic widespread pain: an epidemiological study and a feasibility study
Funder: Department of Health and Social Care

Abstract: Research questionTo understand the role of fibromyalgia syndrome (FMS) and chronic widespread pain (CWP) in the development of cognitive impairment, and identify methods to treat cognitive impairment in these patients.BackgroundFMS and CWP are common conditions, characterised by widespread pain of unknown aetiology, and affect 5% and 14% of UK adults respectively. These patients commonly report difficulty concentrating and memory impairment, typically referred to as 'fibro-fog'. FMS and CWP are associated with impaired performance on objective cognitive tests, although it is uncertain whether there cognitive impairment is global or limited to specific domains. The role of depression and sleep impairment in the development of cognitive symptoms is also uncertain. The long-term cognitive consequences are also unclear, and whether there is an increased risk of dementia. These patients also display alterations in brain structure and function on neuroimaging, but the role of these changes in the development of cognitive impairment is unknown. Although there are many therapies for FMS and CWP, none exist for cognitive symptoms. Psychological therapies, such as cognitive behavioural therapy (CBT), have a role in treatment of FMS, but uptake is limited. Novel digital forms of CBT may be more widely accessible, however these have not been examined before for cognitive symptoms of these disorders.Aims and objectivesTo understand the role of FMS and CWP in the development of cognitive impairment, the underlying mechanisms and mediators in their development, including sleep impairment, and the role of brain structural and functional changes. A feasibility study will establish whether it is possible to conduct a trial of digital CBT targeting sleep disturbance to alleviate cognitive symptoms in patients with FMS.MethodsThe project consists of two studies. Study 1 will use data from UK Biobank, an open-access, population-based study of >500,000 adults aged 40-69. Cross-sectional and longitudinal observational research designs will be employed to examine the association between CWP and FMS with cognitive impairment. The three cognitive endpoints examined will be cognitive performance, changes on structural and functional brain MRI, and risk of incident dementia. Mediation analysis will be performed to examine the role of sleep impairment on the association. Study 2 will be a feasibility study to establish whether it is possible to conduct a trial of digital psychological treatment targeting sleep impairment, which we believe is a mediator to alleviate cognitive symptoms in patients with FMS and CWP. Timelines for deliveryThe literature review and analysis for study 1 will be completed by month 22. Study 2 will be carried out in parallel during months 13-32. The final 6 months will be occupied by the thesis write-up.Anticipated impact and dissemination This work will inform clinical practice for the recognition and treatment of cognitive symptoms in FMS and CWP, an important cause of morbidity for these patients. By addressing these symptoms, greater engagement with other aspects of treatment for these conditions may be achieved, providing health benefits for patients, and more efficient utilisation of health service resources.

Lay abstract: Background Chronic pain is pain that carries on for more than 3 months despite treatment. It can occur following an injury or operation, but sometimes may occur without any known cause. Fibromyalgia and chronic widespread pain (CWP) are common causes of chronic pain, affecting 1-in-20 and 1-in-5 British adults, respectively. These related conditions are characterised by pain all over the body and have no known cause. These conditions are difficult to treat, and can cause lifelong disability and ill-health, placing significant costs on the health service and society.These patients experience many symptoms besides pain, including difficulty concentrating, memory loss, and confusion (often referred to as 'fibro-fog'). We do not know what causes these cognitive symptoms, and they have no available treatments. Need for better understanding of cognitive symptoms We do not know which areas of cognition are worst affected in these patients, and if these symptoms worsen with time. Some small studies have shown that fibromyalgia and CWP patients have changes in their brains on MRI scans. However, we do not know if these changes are in parts of the brain that are important for cognition, and if these changes are the cause of cognitive problems. Depression and sleep problems are common features of fibromyalgia, and are known to be associated with cognitive problems. Treating them may alleviate cognitive symptoms.Need for treatment for cognitive symptomsExisting treatments for fibromyalgia and CWP include exercise, medication, and psychological therapy. However, there are no treatments for the cognitive symptoms. Psychological therapies include cognitive behavioural therapy (CBT), which involves changing harmful thought patterns and behaviours. However, in-person CBT is costly and are difficult to delivery widely. New forms of CBT have been developed which can be delivered via the internet. These may overcome limitations posed by in-person therapy. CBT for insomnia has improved cognitive symptoms in people with insomnia, and may be useful in treating the cognitive symptoms of fibromyalgia and CWP.Patient involvementPatients, clinicians and researchers agree that better management of cognitive symptoms is a top research priority for fibromyalgia. A group of patients living with fibromyalgia from across the UK reviewed this project and advised on the design. They suggested that sleep problems play an important role in their cognitive symptoms, and that treatment for these would be helpful. This group will continue to provide advice during the project. Research aimsMy research aims are to identify the nature and consequences of cognitive symptoms among patients with fibromyalgia and CWP, to identify which areas of the brain are most affected on MRI, and to test digital CBT for insomnia as a treatment for cognitive symptoms.Design and methods I will make key advances by using appropriate methods to measure the features of cognitive impairment in these patients using data from very large population studies. This will include examining the role of depression and sleep impairment, cognition over time, and the areas of the brain that are most changed in these pain disorders. The availability of digital CBT means it is possible to deliver this therapy more widely, and the use of cognitive tests and brain MRI makes it possible to measure treatment response accurately. I will make the first step towards evaluating this treatment by conducting a small-scale study to test whether it would be possible to conduct a larger trial of digital CBT for insomnia in patients with fibromyalgia and CWP. DisseminationI will engage with patient groups such as Fibromyalgia Action UK in order to promote the findings, and participate in patient education programmes. I will publish the results in peer-reviewed journals commonly read within pain medicine.

Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH;DISPUTED AETIOLOGY AND OTHER