TNF inhibitors for the prevention of Alzheimer’s disease: Preliminary findings from the rheumatoid arthritis medication and memory study (RESIST)

Abstract

Background: A raised level of serum TNFα observed in patients with Alzheimer’s disease 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 hypothesis that reduction in peripheral TNFα via TNF inhibitors (TNFi) may reduce the rate of neurodegeneration and may protect against development of AD. Method: The rheumatoid arthritis medication and memory study (RESIST) is an 18-month observational study which aims to compare the rate of cognitive decline between TNFi and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) in patients with both rheumatoid arthritis (RA) and MCI. Participants ≥ 55 years of age were recruited from rheumatology clinics in both Northern Ireland and Southampton and were cognitively assessed using the Free and Cued Selective Reminding Test (FCSRT) and Montreal Cognitive Assessment (MoCA). At the time of analysis n=130 participants had completed a 6-month assessment and n=69 had completed a 12-month assessment. ANCOVA analysis was conducted to calculate the difference in mean (and 95% CI) FCSRT and MoCA scores at both 6- and 12-month timepoints between TNFi and csDMARD treatment groups, adjusting for baseline cognitive scores. Further adjustments were made for age, gender, RA disease activity and other confounding variables. Result: There was no evidence of a difference between TNFi and csDMARD treatment in cognitive outcomes measured by FCSRT (6-month cohort (mean difference 0.58, 95% CI - 1.40, 2.56, p = 0.565); 12-month cohort (mean difference -1.09, 95% CI -3.57, 1.38, p = 0.381)) or MoCA (6-month cohort (mean difference -1.09, 95% CI -3.57, 1.38, p = 0.381); 12-month cohort (mean difference -0.04, 95% CI -1.06, 0.98, p = 0.940)) after adjustment for baseline cognitive scores nor was there a difference in cognitive outcomes between treatment groups after adjustment for additional confounders. Conclusion: This preliminary analysis found little evidence of a relationship between TNFi and better cognitive performance however analysis was limited by lack of power and short follow-up periods. This analysis will be repeated once RESIST has ended to determine if there is any statistically significant cognitive benefit of TNFi treatment after 18-months.

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