TBI and Increased Risk of Non-Alzheimer’s disease dementia in older male twins

Background: Several studies have reported an association between traumatic brain injury(TBI) and increased risk of Alzheimer’s disease(AD) and all cause dementia. Considering the heterogeneous genetic and environmental factors that may contribute to development of dementia, co‐twin control analyses provide a level of control for confounding factors that is difficult to achieve with other case‐control designs. Methods: A total of 8787 members of the NAS‐NRC Twin Registry of Male WWII Veterans born between 1917‐1927 were included in the study. Self or proxy‐reported history of TBI was collected from 1990–2005. In‐person dementia evaluations were conducted in participants’ homes and differential diagnoses and age of onset of dementia were assigned by an expert adjudication panel. Proportional hazard models, adjusting for education and twin strata, were used to estimate the risk of dementia associated with TBI in the full sample. In a subsample, the McNemar’s test was used to examine the association between TBI and dementia within twin pairs to control for shared genetic and environmental risk factors for dementia within the pairs. Results: Of the 8787 men, 25% reported a history of TBI, while 3.8% had AD and 1.9% had other types of dementia. Median age of dementia onset was 75 years. The mean age of first TBI for those without dementia was 33 years (SD=23) and 38 (SD=24) for those with dementia. Hazard models show those with TBI had over twice the risk of being diagnosed with other cause dementia after a TBI (hazard ratio (HR) 2.29; 95%CI,1.2‐4.4), but not for risk of AD (HR 1.08; 95%CI,0.7‐1.6). A total of 108 twin pairs were discordant for presence of TBI and diagnosis of dementia or age of onset of dementia by at least 3 years. Within these twin pairs, TBI was associated with greater risk of other cause dementia (n=40 pairs), McNemar odds ratio (OR) 2.6, 95%CI 1.3‐5.3, but not for AD (n=68 pairs), OR 1.1, 95%CI 0.7‐1.8. Conclusion: Our findings indicate that TBI may be associated with risk of types of dementia other than AD. This result held even after controlling for many unidentified shared genetic and early life environmental factors within twin pairs.

Duke Scholars

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