The possible connection between head trauma and Parkinson's is illustrated — perhaps nowhere more prominently — by Muhammad Ali's diagnosis of young-onset Parkinson's disease (PD) following a career in boxing. Many have wondered whether repeated hits to the head caused his PD. While it's true that environmental factors — including head injury — have been associated with an increased risk of Parkinson's, few (if any) have been determined to be definitive causes of the disease. Environmental factors and genetics may interact to cause disease, and this complex interplay makes it virtually impossible to point to the exact cause(s) in any individual.

Genetics and Environmental Factors May Contribute to Parkinson's

A number of genetic mutations are associated with Parkinson's disease — some simply increase risk for the disease and others appear to be more direct causes. Many environmental factors (e.g., head trauma, pesticides and solvents) are also linked to an elevated risk of Parkinson's. Generally though, these environmental risks are designated as "associations" rather than "causes" (i.e., for some reason they contribute to an increased risk but they are not sufficient to cause PD in and of themselves).

When faced with these types of associations, researchers look to see if there are other variables or reasons — such as general trauma (to the body rather than specifically to the head or brain) — that are a truer or more important basis for the connection. They also aim to exclude "reverse causation" (i.e., undiagnosed Parkinson's disease leading to falls that cause head trauma — rather than vice versa). Genetics may play a more significant role in some cases, particularly in people who have a younger age of disease onset and/or a family history of PD. However, since family members share genes as well as environmental exposures, the latter cannot be excluded as a strong contributing factor.

Evidence Links Head Trauma and Brain Injury to Parkinson's

Research results have been somewhat inconsistent on Parkinson's and head trauma or traumatic brain injury (one that alters consciousness and leads to temporary or permanent cognitive, physical and/or emotional problems). Still, a number of studies have shown a fairly clear link between PD and head or brain trauma (typically secondary to car accidents, falls or sports-related injuries). These studies have compared the history of head trauma or brain injury between groups of people with and without Parkinson's to demonstrate the association.

In an MJFF-funded study comparing twins (only one of whom had PD), the twin who had previously sustained a head injury was more likely to be diagnosed with Parkinson's. The investigators therefore concluded that mild to moderate head injury may heighten the risk of PD. Another review of several published studies confirmed this connection and added that head trauma resulting in concussion is associated with a higher risk of developing PD. A third study reviewed the medical records of people with traumatic brain injury and individuals with trauma unrelated to the brain (e.g., bone fracture). Their results indicated that traumatic brain injury is linked to an increased risk of a subsequent diagnosis of PD and the risk was higher with more severe or recurrent injuries. 

Multiple Possibilities Exist to Explain the Connection between PD and Head or Brain Injury

Despite data suggesting that head injury might cause Parkinson's, it's still plausible that other factors could explain the association. For example, people with Parkinson's might be more prone to brain injury (as discussed above). Or, the brains of those with PD may be more susceptible to trauma and therefore incur more damage than would otherwise be expected.

Other theories proposed to explain the link between head or brain trauma and PD include:

• Trauma uncovers underlying Parkinson's disease. In other words, a person would have developed PD anyway, but the trauma acts as the proverbial "straw that broke the camel's back." It is just one of many factors (e.g., genetics, other environmental insults, etc.) that leads to PD. The relative importance of head injury toward the development of PD may be greater (or less) than other factors, but together they bring about Parkinson's.
• Injury causes destruction of dopamine-producing cells. The mechanism is either direct or indirect — such as by provoking an inflammatory process and/or causing tiny bleeds deep in the brain that eventually scar.

Research on Head Trauma and Parkinson's Is Challenging

Studying this association is difficult for many reasons:

• Determining the type and amount of an individual's exposure to a certain environmental risk typically relies on examination of medical records and/or a person's recollection to report prior events (both of which might be incorrect). Even in boxing, where hits during matches are recorded, those sustained during practice or at other times are typically unknown. Additionally, hits on helmeted boxers or hits that are partially blocked are likely different than unprotected or direct ones. 
• Characterizing the total lifetime exposure (i.e., the number and magnitude of hits to the head) may be very difficult.
• Varying definitions of what constitutes "head trauma" or a "hit" may be used in studies. 
• Aside from the above considerations, it remains nearly impossible to tell whether most people would have developed Parkinson's even without an exposure that is linked to the disease.

Still, researchers are working to uncover details about the relationship of environmental (and genetic) factors and Parkinson's. As they do so, they learn more about potential mechanisms that damage or destroy dopamine-producing cells. This work, some of which MJFF has funded (e.g., both pre-clinical and clinical studies on inflammation and Parkinson's), points toward new therapies that can be tested for PD. A good example of how environmental associations can inform therapeutic development comes through the NIC-PD trial. In looking at large populations of people, researchers noticed that cigarette smoking was associated with a lower risk of Parkinson's. Delving deeper, they postulated that nicotine (rather than other ingredients in smoke or tobacco) might be a protective factor. This led to the current study which is evaluating that idea — that nicotine (in patch form) might slow or stop PD progression. 

In conjunction with searching for disease-modifying therapies, investigators are looking for a biomarker — an objective measurement to diagnose and monitor Parkinson's. This type of indicator could aid clinical management, accelerate research and (especially if it could diagnose PD before symptoms occur) help parse out the association of environmental factors and disease. In one recently completed study (the results of which are pending), researchers evaluated DaTscans in people without PD one year after a mild traumatic brain injury to determine if these specialized brain images could potentially be used for the evaluation of Parkinson's in this context.

To summarize, head trauma and traumatic brain injury are associated with an increased risk of Parkinson's but the mechanisms for how they are connected are unclear and direct causation (head or brain injury actually causing Parkinson’s) has not been established. More work is necessary to fully understand this relationship. 

Read about Muhammad Ali's life and legacy. 

Get involved in research on environmental factors and Parkinson's. 

Learn more about genetics and Parkinson's disease.

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