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Crane PK, Gibbons LE, Dams-O'Connor K, Trittschuh E, Leverenz JB, Keene CD, Sonnen J, Montine TJ, Bennett DA, Leurgans S, Schneider JA, Larson EB. Association of Traumatic Brain Injury With Late-Life Neurodegenerative Conditions and Neuropathologic Findings. JAMA Neurol. 2016 Sep 1;73(9):1062-9. PubMed.
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Mayo Clinic
This is a very interesting article and an important contribution. There is much media attention regarding TBI, CTE, and neurodegenerative diseases among professional and amateur athletes. However, very little research has examined the relationship between TBI and neurodegenerative diseases among the general population. Given the media attention, patients who have a mild TBI are often concerned, some extremely anxious, that they will develop Alzheimer's disease. Indeed, some previous epidemiological studies did report that a history of TBI is associated with an increased risk of AD. However, just as many studies did not find an association.
These discrepant findings reflect methodological variation in defining TBI and AD and related dementia (e.g., Parkinson's disease or Lewy Body Dementia), study populations of TBI cases, classifying TBI severity, and in the types and definitions of controls used. The study populations in previous reports vary widely, including at-risk groups such as active-duty military personnel, veterans, or professional athletes, which are almost exclusively male. Thus, it remains unknown whether the results are generalizable to women, the general population, or even non-active-duty military personal who experience a single mild TBI.
With this background, it is evident why this study is a major contribution to the field. It is by far the largest study to date and includes three separate community-based cohort studies that have well-characterized participants, including cognitive diagnoses and autopsy, with longitudinal follow-up. Their findings suggest that a history of TBI is not associated with an increased risk of AD in community populations. Interestingly the authors also did not find interactions between a history of TBI and either APOE or sex in predicting risk of AD. A few other studies have reported that TBI is a risk factor for AD, especially among those with an APOE E4 allele.
Notably, the authors also did not find an association between TBI and AD pathology. While some other studies have reported such an association, we also did not find an association between a self-reported history of TBI, with at least momentary loss of consciousness, and brain amyloid levels using PiB-PET imaging among cognitively normal individuals enrolled in the population-based Mayo Clinic Study of Aging (Mielke et al., 2014). The similar study designs with consistent outcomes are reaffirming.
This does not, however, mean that TBI has no role in predicting risk of AD. It is still likely that the severity of the injury or the number of injuries could be associated with an increased risk of AD and AD pathology. Further, an important limitation of the study is the self-reported TBI. Additional studies with confirmation of brain trauma and severity, rather than self-reported instances, in the population are needed to elucidate the relationship between TBI and risk of AD for the general population.
The findings with PD and Lewy body pathology are intriguing. However, the sample size is small and the pathological findings are not fully consistent across studies. Large-scale studies are needed to confirm the results.
References:
Mielke MM, Savica R, Wiste HJ, Weigand SD, Vemuri P, Knopman DS, Lowe VJ, Roberts RO, Machulda MM, Geda YE, Petersen RC, Jack CR Jr. Head trauma and in vivo measures of amyloid and neurodegeneration in a population-based study. Neurology. 2014 Jan 7;82(1):70-6. Epub 2013 Dec 26 PubMed.
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