TNF alpha inhibitors in Alzheimer's disease: A systematic review

Objectives
The objective of this study was to evaluate the effect of tumour necrosis factor‐alpha inhibitors (TNF‐αI) on Alzheimer's disease‐associated pathology.
Design
A literature search of PubMed, Embase, PsychINFO, Web of Science, Scopus, and the Cochrane Library databases for human and animal studies that evaluated the use of TNF‐αI was performed on 26 October 2016.
Results
The main outcomes assessed were cognition and behaviour, reduction in brain tissue mass, presence of plaques and tangles, and synaptic function. Risk of bias was assessed regarding blinding, statistical model, outcome reporting, and other biases. Sixteen studies were included, 13 of which were animal studies and 3 of which were human. All animal studies found that treatment with TNF‐αI leads to an improvement in cognition and behaviour. None of the studies measured change in brain tissue mass. The majority of studies documented a beneficial effect in other areas, including the presence of plaques and tangles and synaptic function. The amount of data from human studies was limited. Two out of 3 studies concluded that TNF‐αI are beneficial in Alzheimer's disease patients, with one being an observational study and the latter being a small pilot study, with a high risk of bias.
Conclusion
It was concluded that a large‐scale randomized controlled trial assessing the effectiveness of TNF‐αI on humans is warranted.

This is the peer reviewed version of the following article: Ekert JO, Gould RL, Reynolds G, Howard RJ. TNF alpha inhibitors in Alzheimer's disease: A systematic review. Int J Geriatr Psychiatry. 2018;33: 688– 694, which has been published in final form at https://doi.org/10.1002/gps.4871. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.