The RhEumatoidarthritiS, medIcation and memory STudy (RESIST)
Two distinctive features of the brains of people suffering from Alzheimer’s Disease are amyloid plaques and neurofibrillary tangles. Alongside these changes there is also evidence that inflammation is occurring in the brain (neuroinflammation).
There is increasing evidence that neuroinflammation contributes as much to the disease progression of Alzheimer’s Disease as do the plaques and tangles themselves. A modest increase in the level of a protein in the blood that promotes inflammation: tumour necrosis factor –alpha (TNF-α) has been found to be associated with increased memory decline in people with Alzheimer’s Disease.
TNF-α inhibitors are widely used in the treatment of rheumatoid arthritis, a chronic inflammatory arthritis. TNF-α inhibitors are used to reduce the signs and symptoms of rheumatoid arthritis and to reduce joint damage in people with moderate to severe disease. They are usually prescribed when traditional disease modifying antirheumatic drugs (DMARDs) such as methotrexate do not work. TNF-α inhibitors: etanercept, adalimumab, certolizumabpegol, infliximab and golimumab inhibit the action of TNF, thus suppressing inflammation.
There is a growing evidence base which suggests these drugs may be important in the treatment of Alzheimer’s Disease. A small study has shown that patients taking TNF-α inhibitor drugs for rheumatoid arthritis may be protected against the development of Alzheimer’s Disease by as much as 60%. A small randomised double-blind study of a TNF-α inhibitor (etanercept) showed significant evidence of a slowing down of cognitive decline after regular injections under the skin. This suggests that inhibition of this protein may be an approach to Alzheimer’s Disease treatment.
We have assessed data from the British Society of Rheumatology Biologics Registry-Rheumatoid Arthritis (BSRBR-RA). This registry contains data on 19,000 patients with rheumatoid arthritis on a biologic drug. Those on a TNF-α inhibitor were compared to those on a traditional DMARD. Rheumatoid arthritis patients treated with TNF-α inhibitors appeared to have a lower incidence of dementia compared to traditional DMARD patients.
As a result of this preliminary evidence we are carrying out a comprehensive study, funded by the Alzheimer’s Society, of rheumatoid arthritis patients on TNF-α inhibitors who have early memory problems and following their memory function over 18 months and comparing how well they do with a group of rheumatoid arthritis patients with memory problems who are on traditional DMARDs.
If TNF-α inhibitors are found to reduce the rate of cognitive decline in participants with rheumatoid arthritis who have early memory problems this would give enough evidence for a definitive randomised controlled trial of TNF-α inhibitors in people at risk of dementia.
Participants are now being recruited from rheumatology out-patient clinics in Belfast and Southampton.