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

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

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.

1552-5260
McDowell, Bethany
932608cb-7d23-4f24-b06a-c259597804cf
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Edwards, Christopher J.
dcb27fec-75ea-4575-a844-3588bcf14106
Cardwell, Christopher
61228da9-c290-4297-9869-564cd3af5d9d
McHenry, Michelle
50d67dae-b6bf-41c7-9283-590c5e28785a
Meenagh, Gary
e3d0ae2c-dad3-46dd-8191-1bff3bb70ed0
McGuinness, Bernadette
a4d6fd5f-41c5-4444-a692-931729948f6a
McDowell, Bethany
932608cb-7d23-4f24-b06a-c259597804cf
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Edwards, Christopher J.
dcb27fec-75ea-4575-a844-3588bcf14106
Cardwell, Christopher
61228da9-c290-4297-9869-564cd3af5d9d
McHenry, Michelle
50d67dae-b6bf-41c7-9283-590c5e28785a
Meenagh, Gary
e3d0ae2c-dad3-46dd-8191-1bff3bb70ed0
McGuinness, Bernadette
a4d6fd5f-41c5-4444-a692-931729948f6a

McDowell, Bethany, Holmes, Clive, Edwards, Christopher J., Cardwell, Christopher, McHenry, Michelle, Meenagh, Gary and McGuinness, Bernadette (2021) TNF inhibitors for the prevention of Alzheimer’s disease: Preliminary findings from the rheumatoid arthritis medication and memory study (RESIST). Alzheimer's and Dementia, 17 (S9), [e053595]. (doi:10.1002/alz.053595).

Record type: Article

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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Alzheimer s Dementia - 2022 - McDowell - TNF inhibitors for the prevention of Alzheimer s disease Preliminary findings - Version of Record
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Published date: 31 December 2021
Additional Information: Publisher Copyright: © 2021 the Alzheimer's Association Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

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Local EPrints ID: 455255
URI: http://eprints.soton.ac.uk/id/eprint/455255
ISSN: 1552-5260
PURE UUID: 32ae4be8-360a-4eac-a047-77af12d668ce
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912

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Date deposited: 15 Mar 2022 18:08
Last modified: 17 Mar 2024 02:48

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Contributors

Author: Bethany McDowell
Author: Clive Holmes ORCID iD
Author: Christopher Cardwell
Author: Michelle McHenry
Author: Gary Meenagh
Author: Bernadette McGuinness

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