By Claire Henchcliffe, MD

Associate Professor of Neurology and Neuroscience, Weill Cornell Medical College

Dr. Henchcliffe reports she is on the speakers bureau and advisory board for Teva, IMPAX, and ACADIA, and receives grant/research support from Biogen and Kaneka.

Synopsis: A retrospective study based on an administrative database compared more than 50,000 admissions with traumatic brain injury (TBI) with more than 100,000 admissions for other traumatic injury, and found that TBI in individuals older than 55 years of age led to a 44% increased risk of developing Parkinson’s disease in the ensuing 5-7 years.

Source: Gardner RC, et al. Traumatic brain injury in later life increases risk for Parkinson disease. Ann Neurol 2015; DOI: 10.1002/ana.24396 [Epub ahead of print].

This retrospective study used administrative health data that incorporates all inpatient and emergency department discharge diagnoses for participating states, thus allowing comparison of extremely large patient cohorts. The study focused on individuals at least 55 years old, and identified 52,393 individuals with a diagnosis of traumatic brain injury (TBI) seen from 2005-2006 in California hospitals, either in the emergency department or as inpatients. These were compared with 113,406 individuals who had fractures from trauma but no TBI (non-TBI trauma, or NTT) seen in the same healthcare system and over an identical time period. Diagnoses were all based upon ICD9-CM codes, allowing separation of TBI into mild vs moderate-severe groups, and NTT cases were identified on the basis of ICD9 codes for fractures, but excluding head and neck. The outcome measure of interest was development of Parkinson’s disease (PD) after trauma as identified by ICD9 codes at any emergency or inpatient visit up to 2011. Those with PD or dementia at the time of initial injury were excluded from this analysis. Patients included in the analysis had a mean age of 73.4 ± 11.1 years vs 70.9 ± 10.9 years for the NTT group. Women accounted for notably more in the NTT than TBI group (69% vs 57%, respectively). The majority of traumatic injuries were due to falls (approximately 66%) followed by motor vehicle accidents. TBI patients also had more comorbidities and higher injury severity scores. A total of 2126 PD cases were identified in follow-up. TBI was found to be associated with a 44% increased risk of PD up to 5-7 years after injury, with 1.7% TBI vs 1.1% NTT cases developing (P < 0.001). Moreover, when diagnosed, PD occurred slightly earlier in the TBI vs NTT cases (3.1 years vs 3.4 years). Moreover, within the TBI group, when comparing severity, the risk of developing PD increased approximately two-fold in moderate-severe TBI patients vs mild TBI patients during the follow-up period.

COMMENTARY

Several studies have implicated TBI as a risk factor for PD, but the literature has been fraught with contradictory evidence. One particular criticism leveled at these studies has been that in older adulthood, when many instances of trauma are due to falls, an association might result from trauma as a result of falls from unrecognized PD (that is, reverse causation). The strength of this retrospective study is to compare PD diagnosis between TBI and other types of trauma typically associated with falls. The study design incorporated further safeguards, such as including TBI severity in an effort to test for a “dose-response.” Moreover, the analysis excluded those with PD diagnosed shortly after their traumatic injury, as that could have indicated early PD unrecognized at the time of the initial trauma. Therefore, the study supports a link between TBI and subsequent PD diagnosis, and, as the authors state, this is supported by a recent meta-analysis of 22 studies finding a pooled odds ratio of 1.57 for PD after TBI.1

Weaknesses inherent to the study design include use of ICD9 coding in ascertaining diagnoses, and a lack of data for these same patients in outpatient settings, leading to the possibility of missing PD diagnoses. Nonetheless, it is intriguing to speculate on the nature of the association. One theory is that TBI may trigger a progressive neurodegenerative process. This is supported by animal studies, and α-synuclein deposition has been linked to prior TBI in multiple studies. In an era of increasing recognition of the far-reaching effects of TBI, whether from combat, sports or accidental injury, this is therefore, an important study linking TBI to a disabling neurodegenerative disease.

References

  1. Jafari S, et al. Head injury and risk of Parkinson disease: A systematic review and meta-analysis. Mov Disord 2013;28:1222-1229.