TNF-α Inhibitors and Association of Alzheimer’s Disease. A Systematic Review and a Meta-Analysis.
Shradha Chervittara Karaveetil1, PAVAN KUMARA Kasam Shiva2, Anmol Rao1, Vinay Chandramouli Bellur1, Advaith Rao1, Ananya Prasad1, Era Gupta2, Shreya Narayan2
1MS Ramaiah Medical College, 2Bangalore Medical College and Research Institute
Objective:

To determine whether treatment with a Tumor Necrosis Factor- alpha (TNF-α) inhibitor is associated with a lower risk of Alzheimer’s disease (AD) in patients with inflammatory diseases.


Background:

TNF-α inhibitors are anti-inflammatory medications that are part of standard therapy in patients with inflammatory conditions like Rheumatoid Arthritis and Inflammatory Bowel Disease. Several studies have concluded that patients with inflammatory diseases who are on TNF-α inhibitor therapy show lower rates of developing AD. Since TNF-α  plays a crucial role in AD by promoting neuroinflammatory changes like microglial activation, TNF-α inhibitors could potentially mitigate these effects and reduce the risk of AD in these patients. 


Design/Methods:
We conducted an exhaustive search in various medical databases to identify relevant studies. Studies involved 2 groups i.e. Patients who were on TNF-α therapy and the ones who were not on TNF-α inhibitor therapy, and also assessed the odds of developing Alzheimer's were included in the final review. The statistical analysis was performed in R-Studio. The Mantel-Haenszel method (common effect model) and  Inverse variance method (random effects model) were used to obtain odds ratios.  I^2 test was used to determine the heterogeneity between studies.
Results:

The meta-analysis conducted involved a total of 16,35,474 subjects who were on TNF-α medications and 62865661 subjects who were controls from 4 different studies. There were significantly higher odds of developing Alzheimer's disease in the controls who were not exposed to TNF-α inhibitors in comparison to the ones who were on TNF-α therapy [2.09(0.50;8.71, 95%CI, p < 0.01)] 


Conclusions:

Patients with inflammatory diseases who underwent TNF-α inhibitor therapy showed a reduced incidence of developing AD in comparison to controls. The underlying mechanism could be linked to the anti-inflammatory effects of TNF-α inhibitors preventing neuroinflammation associated with the pathogenesis of AD. Hence, TNF-α inhibitors may have neuroprotective properties contributing to reducing the risk of developing AD.


10.1212/WNL.0000000000212207
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