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Dr. Gregory S. Cooper
“One of the factors that’s seen in the brains of patients with Parkinson’s disease is accumulation of an abnormal protein known as alpha-synuclein,” one of the study authors, Gregory S. Cooper, MD, said during a media briefing in advance of the annual Digestive Disease Week. “It’s released by damaged nerve cells in the brain. Not only is alpha-synuclein found in the brain of patients with Parkinson’s disease; it’s also found in the GI tract. It’s thought that its accumulation in the GI tract occurs prior to the development of its accumulation in the brain.”
This has prompted scientists around the world to evaluate the GI tract, including the appendix, for evidence about the pathophysiology and onset of Parkinson’s disease, said Dr. Cooper, professor of medicine, oncology, and population and quantitative health sciences at Case Western Reserve University, Cleveland. “It’s thought that, potentially, in the presence of inflammation, [molecules] of this protein are released from damaged nerves in the gut and then are transported to the brain, where they accumulate,” he said. “Or, it could be that the appendix is a storage place for this protein and gets released at the time of appendectomy.”
To investigate if appendectomy increases the risk of Parkinson’s disease, Dr. Cooper and colleagues drew from the Explorys database, which contains EHRs from 26 integrated U.S. health care systems. They limited their search to patients who underwent appendectomies and those who were diagnosed with Parkinson’s disease based on Systematized Nomenclature of Medicine–Clinical Terms. The researchers chose a washout period of 6 months to the development of Parkinson’s disease after appendectomy, and compared the prevalence of Parkinson’s disease in the general population to those with appendectomies.
Of the 62,218,050 records in the database, Dr. Cooper and colleagues identified 488,190 patients who underwent appendectomies. In all, 4,470 cases of Parkinson’s disease were observed in patients with appendectomies, and 177,230 cases of Parkinson’s disease in patients without appendectomies. The overall relative risk of developing Parkinson’s disease in patients after appendectomies was 3.19 (95% confidence interval, 3.10-3.28; P less than .0001), compared with those who did not undergo the procedure. The relative risk was higher in patients aged 18-64 years (RR, 4.27; 95% CI, 3.99-4.57; P less than .0001), compared with those 65 years and older (RR, 2.20; 95% CI, 2.13-2.27; P less than .0001). “We know that Parkinson’s disease is more common in the elderly,” Dr. Cooper said. “But at virtually all ages, the prevalence of Parkinson’s disease was higher in patients who had an appendectomy, compared to those without an appendectomy.”
The overall relative risk of developing Parkinson’s disease in patients after appendectomies was slightly higher in females (RR, 3.86; 95% CI, 3.71-4.02; P less than .0001), compared with males (RR, 2.67; 95% CI, 2.56-2.79; P less than .0001). The researchers also observed a similar effect of appendectomy by race. The overall relative risk of developing Parkinson’s disease in patients after appendectomy was slightly higher in African Americans (RR, 3.11; 95% CI, 2.69-3.58; P less than .0001), compared with Asians (RR, 2.73; 95% CI, 2.19-3.41; P less than .0001), and whites (RR, 2.55; 95% CI, 2.48-2.63; P less than .0001).
“If these data get borne out, it may question the role of doing a discretionary appendectomy in a patient who’s having surgery for another reason,” Dr. Cooper said. “Our research does show a clear relationship between appendectomy and Parkinson’s disease. However, at this point, it’s only an association. As a next step, we’d like to conduct additional research to confirm this connection and better understand the mechanisms involved.”
He pointed out that, because of the nature of the Explorys database, he and his colleagues were unable to determine the length of time following appendectomy to the development of Parkinson’s disease.
The study’s lead author was Mohammed Z. Sheriff, MD, also of Case Western Reserve University, Cleveland. The researchers reported having no financial disclosures.
SOURCE: Sheriff MZ et al. DDW 2019, Abstract 739.