A history of head trauma may predict a more rapid decline in patients with Parkinson’s disease (PD), new research suggests.

In a longitudinal online study, among patients with PD who had a history of head injury, motor impairment developed 25% faster and cognitive impairment developed 45% faster than among those without such a history.

In addition, severe head injuries were associated with an even more rapid onset of impairment.

The results give weight to the idea that “it’s head injuries themselves” prior to the development of PD that might exacerbate motor and cognitive symptoms, study investigator Ethan Brown, MD, assistant professor, Weill Institute of Neurosciences, Department of Neurology, University of California, San Francisco, told Medscape Medical News.

The findings emphasize the importance of “doing everything we can” to prevent falls and head injuries for patients with PD, Brown said.

The findings were presented at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2022.

Reverse Causality Concerns

Head injury is a risk factor for PD, but its relationship to PD progression is not well established. “There has always been this concern in PD that maybe it’s problems with motor impairment that lead to head injuries, so reverse causality is an issue,” said Brown.

“We wanted to look at whether risk factors we know relate to the development of PD can also have a bearing on its progression,” he added.

The analysis was part of the online Fox Insight study that is evaluating motor and nonmotor symptoms in individuals with and those without PD. The study included participants who had completed questionnaires on such things as head trauma.

The study included 1065 patients (47% women; mean age, 63 years) with PD who reported having had a head injury at least 5 years prior to their diagnosis. Among the participants, the mean duration of PD was 7.5 years.

The investigators employed a 5-year lag time in their study to exclude head injuries caused by early motor dysfunction, they note.

“We wanted to look at people who had these head injuries we think might be part of the cause of PD as opposed to a result of them,” Brown said.

In this head injury group, 51% had received one head injury, 28% had received two injuries, and 22% had received more than two injuries.

The study also included 1457 participants (56% women; mean age, 65 years) with PD who had not had a head injury prior to their diagnosis. Of these patients, the mean time with a PD diagnosis was 8 years.

Brown noted that the age and sex distribution of the study group was “probably representative” of the general PD population. However, because the participants had to be able to go online and complete questionnaires, it is unlikely that among these patients, PD was far advanced, he said.

The investigators adjusted for age, sex, years of education, and PD duration.

Two-Hit Hypothesis?

The researchers compared time from diagnosis to the development of significant motor impairment, such as the need for assistance with walking, and cognitive impairment, such as having a score of <43 on the Penn Daily Activities Questionnaire.

They also examined the role of more severe head injuries. In the head injury group, over half (54%) had had a severe head injury, including 543 who had lost consciousness and others who had suffered a fracture or had had a seizure.

Results showed that the adjusted hazard ratio (aHR) for developing motor impairment among those with a head injury in comparison with those who had not had a head injury was 1.24 (95% CI, 1.01 – 1.53; P = .037). For severe injuries, the aHR for motor impairment was 1.44 (95% CI, 1.13 – 1.83; P = .003).

For cognitive impairment, the aHR for those with vs without head injuries was 1.45 (95% CI, 1.14 – 1.86; P = .003); and for severe injuries, the aHR was 1.49 (95% CI, 1.11 – 2.0; P = .008).

Aside from severity, the researchers did not examine subgroups. However, Brown reported that his team would like to stratify results by sex and other variables in the future.

He noted that various mechanisms may explain why PD progression is faster for patients who have a history of head injury in comparison with others. Chronic inflammation due to the injury and “co-pathology” might play some role, he said. He noted that head injuries are associated with cognitive impairment in other conditions, including Alzheimer’s disease.

There is also the “two hit” hypothesis, Brown said. “A head injury could cause such broad damage that once people develop PD, it’s harder for them to compensate.”

Brown also noted there might have been a “higher magnitude” of a difference between groups had the study captured participants with more severe symptoms.

“Provocative” Findings

Commenting for Medscape Medical News, Michael S. Okun, MD, medical advisor at the Parkinson’s Foundation and professor and director at the Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, said the new data are “provocative.”

“The idea that a head injury may be important in predicting how quickly and how severely deficits will manifest could be important to the treating clinician,” said Okun, who was not involved with the research.

He noted that the results suggest clinicians should elicit more information from patients about head trauma. “They should be seeking more than a binary ‘yes or no’ answer to head injury when questioning patients,” he added.

Okun reiterated that head injury is a “known and important risk factor” not only for PD but also for other neurodegenerative diseases. “It’s important to counsel patients about the association,” he said.

The study was supported by the Michael J. Fox Foundation. Brown reports having received grant support from the Michael J. Fox Foundation. Okun has reported no relevant financial relationships.

International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2022: Abstract 1178. Presented September 17, 2022.

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