Comment: Type 1 diabetes, traumatic brain injury, and dementia: Interactions or just bad luck?

A remote history of traumatic brain injury (TBI) has been shown in numerous studies to confer an increased risk for dementia. Gilsanz et al.1 now report results from a study of individuals with type 1 diabetes, finding that those who had sustained a TBI experienced “a marked increase in risk of dementia” relative to those without such a history. The risk level (hazard ratio 3.64) exceeds most previously reported associations within the general population, raising intriguing questions regarding possible pathophysiologic mechanisms. Strengths of the study include the use of the established, rich electronic database of the Kaiser Permanente Northern Health Plan that has previously been used for other studies to examine risk factors for dementia.2 Robust criteria for type 1 diabetes and comprehensive information on potential confounders were available. Reliance on electronic records for TBI history may selectively ascertain more severe cases, and this might bias results away from the null. TBI within 1 year before dementia diagnosis was included in some analyses, contrary to many previous studies, and results of brain imaging were unavailable. Why is the estimate of dementia risk after TBI so high in this study? Reduced brain reserve associated with type 1 diabetes or exacerbated underlying neurotoxicity are among several eminently plausible explanations. Methodologic and demographic differences constrain direct comparison of the risk size estimates of this with those of studies among nondiabetic patients. The results of the Gilsanz et al. study have important and well-described clinical implications for people with type 1 diabetes. The hint provided by this fascinating study that type 1 diabetes and TBI may interact in the pathogenesis of dementia clearly warrants further investigation in more representative samples where unbiased estimates of dementia incidence following TBI can be obtained for those both with and without type 1 diabetes, using the same methodology.

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