TNF inhibitors for the prevention of Alzheimer’s disease

  • Bethany McDowell

Student thesis: Doctoral ThesisDoctor of Philosophy


In recent years, genome-wide association studies have identified polymorphisms in several genes which implicate the role of inflammation in the development and progression of Alzheimer's disease (AD). This is of particular relevance in rheumatoid arthritis (RA), a chronic inflammatory autoimmune disease, as these patients have higher levels of systemic inflammation than the general population. If AD is driven by inflammation, then RA may be the ideal model in which to observe the accelerated effects of systemic inflammation on cognitive decline for future interventional trials. Moreover, there have been several inflammatory biomarkers which have been found to be peripherally elevated in both diseases including tumour necrosis factor-alpha (TNFa), a proinflammatory cytokine which has been associated with an increased rate of neurodegeneration and risk of conversion from mild cognitive impairment (MCI) to AD dementia. This led to the development of a hypothesis which suggested that reduction in peripheral TNFa via TNF inhibitors (TNFi) may slow or prevent cognitive decline associated with AD. This thesis aimed to test this hypothesis by using preliminary data from the rheumatoid arthritis medication and memory study (RESIST), an 18-month observational study which aims to compare the rate of cognitive decline between TNFi and conventional synthetic anti-rheumatic drugs (csDMARDs) in patients with both RA and MCI. While analysis of screening data was able to demonstrate high prevalence of cognitive impairment in this RA population, analysis of preliminary longitudinal data found little evidence of a relationship between TNFi and better cognitive performance after 6/12 months. This analysis will be repeated using 18-month data when available which will more fully describe the relationship between TNFi and cognitive outcomes. Nevertheless, this preliminary research is a valuable contribution in a topic that is largely under researched and will help to inform future longitudinal studies of TNFi as a preventative treatment for AD.
Date of AwardDec 2021
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SponsorsAlzheimer's Society, Research and Development Office for Health and Social Care & Queen's University Belfast
SupervisorChristopher Cardwell (Supervisor) & Bernadette McGuinness (Supervisor)


  • Alzheimer’s disease
  • mild cognitive impairment
  • rheumatoid arthritis
  • inflammation
  • TNFa
  • TNF inhibitors

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