Discussion
The major findings from this retrospective population-based cohort study are the associations between the occurrence of concussion and an increased risk of diagnosis of ADHD, MADs, dementia and PD by factors of 1.4, 1.7, 1.7 and 1.6, respectively. Moreover, these findings were minimally affected when controlling for socioeconomic status (SEFI-2) and overall health status (CCI).
Comparisons are difficult to make with other studies, given the limited number of studies using similar methodologies. Nevertheless, our results are similar to those from studies with a focus on concussion-specific injuries that were identified from medical registries.8 12 13 30 However, our study includes individuals of all ages and not select age groups.8 13 30 Our results, which suggest stronger associations between concussion and risk of diagnosis of ADHD and MADs for women than for men, are difficult to compare with previous research given the paucity of information in this area. The increased strength of association between multiple concussions and risk of diagnosis of MADs, dementia and PD as compared with a single concussion are similarly difficult to compare with previous research.
Earlier findings indicate that comorbidity exists between the conditions of interest included in the present study,31–36 owing, in part, to a commonality in symptoms.37–40 Thus, our results indicating a decrease in strength of association between concussion and risk of diagnosis of the condition in question by up to 19% when adjusting for the diagnosis of one of the other conditions of interest in the time to follow-up are not unexpected. While these findings support the idea of comorbidity between conditions, concussion continued to be associated with an increased risk of diagnosis for all four conditions of interest, suggesting that concussion may therefore be a risk factor for ADHD, MADs, dementia and PD, regardless of the presence of comorbid conditions. Unfortunately, the specific mechanisms resulting in these changes in strength of association are unknown, but it remains possible that dysregulation of pathways of various biomarkers involved in the conditions of interest in the present study—namely, cortisol, may also be affected following a concussion.41–43
Previous research has identified a decrease in strength of association between mild traumatic brain injuries and subsequent risk of diagnosis of either MADs12 or dementia13 as the time between diagnoses increases. We report similar findings, although specific for concussions and with a more gradual decrease in association over time, likely attributable to the differences in injury severity between studies.
The results from the first sensitivity analysis indicating that concussion-associated risk of diagnosis of ADHD was stronger for younger age groups and that older age-groups had stronger associations between concussion and risk of diagnosis of either dementia or PD are not unexpected. Indeed, ADHD is more prevalent in younger people,27 whereas dementia and PD typically affect older individuals.26 Results from the second sensitivity analysis revealed stronger associations between concussion and risk of diagnosis of MADs and dementia for incident concussions diagnosed during or after 1998 compared with those diagnosed before 1998. These differences are probably a byproduct of an increased number of diagnoses in recent years— namely, in adolescents,1 40 which itself may be partially attributed to improved awareness and knowledge of concussions and their associated signs and symptoms.44 It is also possible that advancements in clinical diagnostic parameters have contributed to these findings.6 45
Limitations
One of the limitations with the present study is that ICD-9-CM codes from the Medical Services database are restricted to the first three digits. It is therefore possible that some individuals may have experienced injuries more severe than a concussion. In order to mitigate any effect this might have had on our results, medical records indicating a concussion were limited to in-office visits, where the likelihood of a serious traumatic event is minimal.
Another limitation is that medical data was restricted to the years 1990–1991 to 2014–2015 (inclusive). We were therefore limited in our ability to account for each individual’s previous medical history. Thus, CCI was included as a surrogate measure of health status and included in our analyses as a confounding variable.
The authors acknowledge the potential genetic and familial aspects of concussion46 and the various outcomes discussed in the present study,47–51 but the assessment of such factors was beyond the scope of this study.
The data in this study do not include post-mortem diagnoses. Although it is possible that various conditions may be diagnosed after death, it is believed that the number of diagnoses made post mortem would not significantly change our results.
Some of the data included in our study may pertain to individuals who were not born in the Province of Manitoba but moved to Manitoba later in life, potentially leading to an under-reporting of concussions and/or conditions of interest. Follow-up analyses have shown that the date of health insurance coverage was the same as an individual’s date of birth for ~50% of individuals in both the matched control and concussion groups, mitigating any impact on our findings.