A DIAGNOSIS OF rheumatoid arthritis usually portends a lifetime of medication and lifestyle modification to prevent the potentially crippling side effects of the disease.
And according to Dr. Brian Bowers, a rheumatologist and clinical assistant professor of medicine at the University of South Dakota Sanford School of Medicine, it may also mean an increased chance of getting Alzheimer’s disease.
“Physicians and researchers have suspected there may be a link between RA and Alzheimer’s disease,” Bowers says, noting that “the data was a bit conflicting until a 2016 Dartmouth [study] suggested there is an increased incidence of Alzheimer’s disease in individuals with RA.”
To understand how and why RA and Alzheimer’s disease may be linked, it helps to know something about RA’s mechanism of action.
Although RA is a form of arthritis, the damage it produces is not the result of mechanical wear and tear on the joints. Rather, RA is a chronic autoimmune disease, which means the immune system mistakenly attacks its own healthy tissue as if it were a foreign substance. The reasons why the immune system turns on its host are poorly understood.
The mechanism of action is better defined. When RA strikes, it promotes the release of proteins, called cytokines, that cause widespread inflammation throughout the body. This inflammation targets the tissue lining the joints, causing pain, stiffness, swelling and disfigurement. But the inflammation isn’t just confined to the joints. It also targets many of the body’s organs, including the heart, lungs, blood vessels, bones and skin.
And the brain may also be on that list. “Inflammation has been shown to increase the production and deposition of amyloid proteins,” Bowers says. “The discovery of amyloid plaques in the brains of individuals affected by Alzheimer’s disease has piqued [researchers’] curiosity about the connection between longstanding, untreated RA and the development of Alzheimer’s,” he explains.
“Alzheimer’s disease is characterized by cognitive decline, [and] the cause of [this] decline has been difficult to figure out,” says Bowers, who is also the medical director of the Infusion Center at Rapid City Regional Hospital.
It appears that many factors are responsible for sparking the development of both Alzheimer’s disease and RA. “It has been proposed that there is a genetic predisposition to both conditions, but that both conditions require an environmental trigger,” Bowers explains. Researchers have proposed that various triggers, such as common viral infections, may be responsible for starting the inflammatory process in RA. “It will be interesting if Alzheimer’s researchers also find the trigger that causes cognitive decline and subsequent development of amyloid plaques.”
“One specific cytokine, tumor necrosis factor alpha, is an important [contributor to] the inflammatory process of RA,” Bowers explains. Studies have also shown that it appears to play a role in the development of Alzheimer’s disease, and this may explain some of the association noted between RA and Alzheimer’s.
Not everyone is convinced, however. Dr. Rajat Bhatt, a rheumatologist with Columbia Rheumatology in Richland, Washington, needs further proof. “There are reports, but there is no clear link,” he says. In fact, he says some research points to a lower incidence of Alzheimer’s disease in people with RA.
Nonetheless, the association between tumor necrosis factor alpha and Alzheimer’s disease is an area of increasing interest in Alzheimer’s research.
Interestingly, Bowers notes that the Dartmouth study suggested that treating RA with a biologic medication that targets tumor necrosis factor also appears to decrease the incidence of Alzheimer’s disease. In particular, the study noted that etanercept – or Enbrel – had this effect.
Again, Bhatt is unconvinced. “There are no clear studies to support this,” he says.
Clearly, more research is needed. In the meantime, Bowers recommends that patients with RA and a diagnosis of Alzheimer’s disease, or even those showing signs of the disorder, should have a treatment plan individualized to the patient.
“The treatment plan should be team-based,” he says. “The rheumatologist should work hand in hand with the primary care provider or geriatrician, and with physical therapy, occupational therapy and nutrition.”
He stresses the importance of discussing treatment goals, such as symptom control and protecting the joints from damage, while addressing the cognitive changes that come with Alzheimer’s disease to keep the patient safe and decrease the chance of delirium.