Parkinson’s Disease: The Risk Factors

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By Mary Carpenter

“NEUROLOGICAL journals are littered with studies that contradict each other,” wrote L.A.Times reporter and Parkinson’s disease (PD) sufferer Joel Havemann in his 2002 book, A Life Shaken. Havemann is referring to the quest for underlying causes of the depletion of the neurotransmitter dopamine that causes PD symptoms. He ends the book on a hopeful note, writing that “Parkinson’s research is bursting”—but there has been little progress in the intervening 20 years.

What has changed is the numbers. Generally thought to be rare and to occur mostly in the elderly, PD is still most common among those over age 80, and more common among men than women —but is on the rise among all ages, including those under 65.

Most recently, following Covid infection, several younger adults (who had no previous clinical signs of PD and no family history) have developed PD symptoms—which supports earlier evidence for the role of viral infections and immune system activity in causing the disease, according to Patrik Brundin, director of the Center for Neurodegenerative Science in Grand Rapids, Michigan.

“Neurological disorders are now the leading source of disability globally, and the fastest growing…is Parkinson disease,’ write University of Rochester neurologist Ray Dorsey and others in the Journal of Parkinson’s Disease. From 1990 to 2015, the worldwide number of people with PD doubled to over six million, the authors write, “fueled by aging populations, increasing longevity, declining smoking rates, and the by-products of industrialization.”

Data from Blue Cross Blue Shield on the “commercially insured population” showed a 50% increase in the prevalence rate of PD among ages 30 to 64 in the five years from 2013 through 2017, according to its “Health of America” Report. The Report also noted higher rates in northeastern and midwestern states—with the highest in Vermont  (9.9 people/100,000), compared with the lowest in Missouri and Montana (5/1/100,000).

In the rising rate of PD, an estimated 12% is due to increasing longevity, 10% to decreased rates of smoking and about 10% due to environmental factors, according to the Dorsey paper. Prominent among environmental risks is the solvent trichlorethylene—with global use increasing by two percent each year in the semiconductor industry.

PD is the only neurological disease with an incidence that increases along with per capita GDP and along with decreased rates of smoking. Both cigarettes and caffeine have potential neuroprotective effects but their role in PD has not been proven; nor has that of other likely risk factors, such as previous head trauma and having close relatives with the disease.

Nailing down risk factors as well as early biomarkers for PD could help with earlier diagnosis of disease, which currently depends on observation of PD symptoms. But by the time of a PD diagnosis, there has been a 50 to 70% reduction of the brain’s production of dopamine, and a 30 to 50% loss of neurons in the brain that rely on dopamine—deficits that interfere with brain signaling involved in movement.

Movement-related symptoms of PD include tremor, slowed movement (bradykinesia), rigid muscles (dystonia), loss of automatic movements like swinging the arms while walking and changes in speech and writing–although in younger adults, PD symptoms more often begin with dystonia (stiffness or cramping in the muscles or limbs) or dyskinesia (involuntary body movements).

Previous reports of influenza patients experiencing Parkinson’s-like symptoms (tremors and walking disturbances) revealed a possible role in PD for viral infection and specifically of the inflammatory reaction of the body’s immune system.

And the increase in immune system cells in the brains of PD patients are similar to aggregates of those cells found in the brains of patients with autoimmune diseases, such as rheumatoid arthritis, according to German neuroscience researchers at Erlangen University. In lab experiments, “aggressive” T cells in skin samples from PD patients killed “a large number of nerve cells” —compared to cells from healthy test subjects.

In addition, a sleep disturbance that can arise before a PD diagnosis—along with other non-motor symptoms that include constipation, depression and loss of smell—provides early evidence of dopamine depletion accompanying increased inflammation in the brain. With Rapid Eye Movement Sleep Behavior Disorder (RBD), patients physically enact their dreams using vocalizations and movements.

Among patients with RBD —of whom approximately 90% will receive a diagnosis of a Parkinson’s-related disorder within 10 years—alterations in immune cells in the blood, called monocytes, may provide early signs of PD. Explains Marina Romero-Ramos at Denmark’s Aarhus University, the blood indicators suggest the possibility of early PD treatment using immunotherapy “that modulates cells in the blood, which subsequently would stop or delay the changes in the brain.”

In the cases of PD in younger Covid patients, three cases published to date, ages 35, 45 and 58, and a fourth unpublished, brain imaging revealed classic signs of Parkinson’s, and two of the patients responded to drugs given for PD. Among many possible explanations, these patients may have had undetected or pre-symptomatic PD, an ongoing neurodegenerative process that was accelerated by Covid, explains Brundin.

But the “known association between inflammation and an increased risk of Parkinson’s disease” suggests that the immune response to a Covid infection could potentially trigger Parkinson’s,” according to Brundin and colleagues. Another connection: some research suggests that the progression of Parkinson’s disease may begin in the olfactory system—often affected in Covid patients, who lose their sense of smell and taste—indicating that the Covid virus could access the same brain pathways associated with Parkinson’s disease.

“The Parkinson pandemic is preventable, not inevitable,” write Dorsey and colleagues, who encourage activism along the lines of other pandemics including polio, breast cancer and HIV.  Prevention should include reducing or eliminated chemicals known to increase the risk but also improving understanding of root causes including both environmental and genetic.

While experts have long suspected some role of the immune system in PD, researchers are still working to nail down causes and better treatments in much the same way they were by the time Joel Havemann died from PD a few years ago. But for the rest of his life, Havemann continued to talk, in the same way he concluded his 2002 book, about “what the disease has meant to me…a new respect for the human mind…a deep appreciation of family. Reverence for nature… Admiration for humanity.”

—Mary Carpenter regularly reports on topical subjects in health and medicine.