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February 7, 2018

Traumatic Brain Injury With Loss of Consciousness Can Lead to an Earlier Onset of Alzheimer's Disease

Cover of Neuropsychology (small)With the growing number of traumatic brain injury (TBI)-related emergency department visits, increasing awareness of concussion, and a rapidly growing elderly population, a hot topic in the general public and scientific circles is the association between TBI and increased risk of dementia.

Although some of the most publicized findings have been on the controversial link between concussions and chronic traumatic encephalopathy (CTE), the number one cause of dementia is Alzheimer's disease (AD), which accounts for 50–75% of all dementia cases and constitutes more than 5 million people in the United States alone.

Most research evaluating the risk of AD following TBI has exclusively used clinical diagnostic criteria for AD, and findings have been mixed. Unlike previous studies, the authors of a recent article published in Neuropsychology examined autopsy-confirmed AD cases from a large multi-site national dataset to evaluate the age of cognitive decline and age of diagnosis of AD in those with and without a history of TBI with loss of consciousness (LOC).

By using autopsy-confirmed cases of AD, Schaffert and colleagues (2018) sought to explore the link between TBI and AD versus non-specific causes of dementia.

Three overlapping autopsy-confirmed AD samples were derived from the National Alzheimer's Coordinating Center database. The samples were dichotomized based on a self or caregiver report of the presence or absence of a history of TBI with LOC, and further categorized based on the degree of AD pathology found at autopsy, i.e., intermediate (N = 2,153) and high (N = 1,496), as well as a more "pure" sample of "high degree" cases, with other pathologies excluded (N = 820).

Those with a higher degree of AD neuropathology at autopsy had a younger age of onset of cognitive decline and younger age of diagnosis. Statistically controlling for the effects of gender, race, and years of education on age of onset, the authors found that across the three samples, the average age of estimated symptom onset and age of diagnosis was significantly earlier (~2.5 to 3.5 years) in those with a history of TBI versus those without.

Although these findings cannot be used to determine individualized risk for earlier AD onset following TBI, they do suggest that TBI is one risk factor that seems to be related to an earlier expression of AD. Previous research suggests that the age at injury, number of injuries, and injury severity may moderate the risk of dementia, although genetic and other factors may play a role.

TBI has been hypothesized to increase late-life dementia risk by lowering cognitive or neuronal reserve, initiating a neurodegenerative process, and/or accelerating an underlying neurodegenerative process.

The authors suggest that prospective designs which better identify specific TBI characteristics, evaluate the course of cognitive decline after TBI, and utilize neuroimaging, biomarker, and autopsy data would help determine why some individuals may be at greater risk of earlier AD onset following TBI.


  • Schaffert, J., LoBue, C., White, C. L. III, Chiang, H.-S., Didehbani, N., Lacritz, L., Rossetti, H., Dieppa, M., Hart J. Jr., Cullum, C. M. (2018). Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer's disease. Neuropsychology, 32(4), 410–416. http://dx.doi.org/10.1037/neu0000423

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Note: This article is in the Neuroscience & Cognition topic area. View more articles in the Neuroscience & Cognition topic area.