Traumatic brain injury in the prodromal period of Parkinson's disease: A large epidemiological study using medicare data

Abstract

Objective Studies suggest a greater risk of Parkinson disease (PD) after traumatic brain injury (TBI), but it is possible that the risk of TBI is greater in the prodromal period of PD. We aimed to examine the time-to-TBI in PD patients in their prodromal period compared to population-based controls. Methods We identified 89,790 incident PD cases and 118,095 comparable controls > 65 years of age in 2009 using Medicare claims data. Using data from the preceding five years, we compared time-to-TBI in PD patients in their prodromal period to controls. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for TBI in a Cox regression, while adjusting for age, sex, race/ethnicity, modified Charlson comorbidity index, smoking, and alcohol use. Results Risk of TBI was greater in PD patients in their prodromal period across all age and sex groups, with HRs consistently increasing with proximity to PD diagnosis. HRs ranged from 1.64 (95% CI 1.52, 1.77) five years prior to diagnosis to 3.93 (95% CI 3.74, 4.13) in the year prior. The interaction between PD, TBI, and time was primarily observed for TBI attributed to falls. Motor dysfunction and cognitive impairment, suggested by corresponding ICD-9 codes, partially mediated the PD-TBI association. Interpretation There is a strong association between PD and a recent TBI in the prodromal period of PD. This association strengthens as PD diagnosis approaches and may be a result of undetected non-motor and motor symptoms, but confirmation will be required.

Validation of a Parkinson Disease Predictive Model in a Population-Based Study

“…Earlier identification of PD could have important public health impact. First, earlier identification of individuals with prodromal PD may reduce morbidity and mortality through early treatment, given the growing evidence that prodromal PD patients have a greater risk of fall-related traumatic injuries than the general population [2][3][4]. Second, earlier PD identification would likely reduce the amount of diagnostic testing that prodromal PD patients often undergo as a consequence of the symptoms of undiagnosed PD.…”

“…e period preceding PD diagnosis in which these symptoms occur, called the prodromal period, may predate the diagnosis by decades [1]. Traumatic brain injuries [2], fractures [3,4], and injurious falls more generally [4] occur more frequently among individuals with undiagnosed PD relative to comparable individuals without PD. Motor symptoms occur for at least five years prior to PD diagnosis [5], and the increased risk of fractures among prodromal PD patients begins ∼6-7 years prior to PD diagnosis [3].…”

“…Motor symptoms occur for at least five years prior to PD diagnosis [5], and the increased risk of fractures among prodromal PD patients begins ∼6-7 years prior to PD diagnosis [3]. Accordingly, tools to facilitate early PD diagnosis could have both broad application and potentially important public health impact, for example, through a reduction in fall-related morbidity [2][3][4][5][6][7]. Since the motor symptoms are primarily due to loss of dopaminergic neurons in the substantia nigra, motor symptoms during the prodromal period are likely to be responsive to dopaminergic therapy.…”

Inhibition of Lats1/p‐YAP1 pathway mitigates neuronal apoptosis and neurological deficits in a rat model of traumatic brain injury

“…In this model, rats with brain injury showed obvious neuronal apoptosis and neurological dysfunction. Many studies on TBI patients prove that neuronal cells death and subsequent neurological deficits following TBI contribute significantly to increase TBI patients mortality, long‐term disability, and a series of complications, such as communication barriers, sensory, and behavioral disorders, and an increased risk for chronic CNS diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD) . Therefore, efforts to improve apoptosis and neurological dysfunction imminently need to clarify the potential cellular and molecular mechanism.…”

Therapeutic implications of how TNF links apolipoprotein E, phosphorylated tau, α‐synuclein, amyloid‐β and insulin resistance in neurodegenerative diseases

“…Also, these conditions predispose to one another, for example, stroke to AD (Henon et al ., ) and TBI to PD in older individuals (Gardner et al ., ), with a more recent study (Camacho‐Soto et al ., ) finding the link to be stronger during the prodromal period. Similarly, TBI predisposes to AD (Fleminger et al ., ).…”