Inflammatory Conditions Linked to Higher Risk of Alzheimer’s
Patients with inflammatory diseases such as rheumatoid arthritis or psoriasis have a higher risk of developing Alzheimer’s disease, which can be reduced by treatment with tumor necrosis factor (TNF) inhibitors.
That finding, “Tumor Necrosis Factor (TNF) Blocking Agents Reduce Risk for Alzheimer’s Disease in Patients with Rheumatoid Arthritis and Psoriasis,” was published in the journal medRxiv and presented in a scientific poster, (page 138) during the 12th Clinical Trials on Alzheimer’s Disease Meeting (CTAD), held in San Diego, California, in December.
Alzheimer’s progression involves inflammatory changes in the brain, which are thought to be driven, at least in part, by the overproduction of pro-inflammatory molecules like TNF.
Excessive production of TNF is the root cause of many inflammatory diseases, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis, psoriatic arthritis, ulcerative colitis (UC) and Crohn’s disease (CD). These diseases can be treated effectively with TNF blocking agents.
“TNF produced systemically [as in patients with inflammatory diseases] may directly enter the brain (…) and affect inflammatory processes in the brain relevant to Alzheimer’s disease,” the researchers wrote.
To test if patients with pre-existing inflammatory diseases have a higher risk of developing Alzheimer’s and if this risk could be reduced by treatment with TNF inhibitors, investigators at Tetra Therapeutics, in collaboration with colleagues at Case Western Reserve University and The MetroHealth System, reviewed the medical records of 56 million patients with various types of inflammatory diseases.
Anonymous electronic health records were collected using the IBM Watson Health Explorys Cohort Discovery platform, which contains data from 360 hospitals and 317,000 providers.
Findings showed that RA increased the risk of Alzheimer’s by 2.06-fold, as did AS (by 1.57-fold), psoriasis (by 1.37-fold), UC (by 1.82-fold), and CD (by 2.33-fold).
“Our analysis demonstrates the value of a large, population-based database covering 20% of the entire US population. We find that inflammation in the body increases risk for Alzheimer’s disease across multiple diseases involving the joints, the gut and the skin,” Mark E. Gurney, PhD, said in a press release. Gurney is chairman and CEO of Tetra Therapeutics and co-author of the study.
Next, researchers examined whether the risk of Alzheimer’s could be reduced by inhibiting the activity of TNF with an FDA-approved blocking agent.
They discovered that among those with RA, etanercept (sold as Enbrel by Amgen) reduced the risk of Alzheimer’s by 66%, adalimumab (sold as Humira by Abbvie) by 72%, and infliximab (sold as Remicade by Janssen) by 48%. Likewise, among those with psoriasis, etanercept lowered the risk of Alzheimer’s by 53%, and adalimumab by 59%.
Methotrexate (brand name Otrexup, among others), an anti-rheumatic medicine, also was found to reduce the risk of Alzheimer’s, especially among those who had been prescribed a TNF inhibitor and methotrexate.
While sex or race did not have a significant impact on the effects of treatment, younger patients seemed to benefit more from TNF inhibitor treatment than older patients.
“The results of our retrospective study need to be validated by well-controlled, prospective studies, but offer the hope that Alzheimer’s disease can be prevented in some patients in whom an inflammatory disease is a risk factor for developing Alzheimer’s disease,” Gurney said.
“The study findings are exciting in that we clearly see that TNF blocking agents reduce the risk for co-morbid Alzheimer’s disease in real-world patients diagnosed with rheumatoid arthritis or psoriasis,” said Rong Xu, PhD, associate professor at the School of Medicine at Case Western Reserve University and co-author of the study.
“Given that anti-TNF biologics are powerful drugs, we believe further prospective studies are necessary to understand their potential in treating or preventing Alzheimer’s disease,” Xu said.