Can Traumatic Brain Injury Lead to Alzheimer's Disease?

Though traumatic brain injury (TBI) has been widely recognized as a leading cause of death and disability around the world, there is still considerable controversy about long-term consequences. Not only are severe head injuries the leading cause of coma, but they are also the leading cause of lasting brain damage in children and young adults. This can mean years of rehabilitation and occupational therapy just to help injured patients regain lost functioning, assuming they ever can.

While 70 to 90 percent of all head injuries are deemed to be mild, the effects of even concussions cannot be underestimated, especially if they occur on a frequent basis. As a result, In recent years, more attention than ever is being paid to the possible long-term effects of TBI on people in high-risk occupations where repeated head injuries are common. This includes professional sports, people in combat roles, and other jobs where physical injuries can occur.

But there are other aspects of serious head injuries that are just beginning to be understood. This includes the potential role that head injuries may play in later cognitive problems ranging from mild cognitive impairments to full-blown dementia, including Alzheimer's disease (AD). Though real evidence of a link between mild concussions and dementia is limited (so far), studies have indicated that medium to severe head injuries can increase dementia risk significantly.

Much of this evidence comes from autopsy-based and imaging studies showing clear pathology related to different kinds of dementia. In looking at Alzheimer's disease specifically, studies suggest that a single moderate to severe head injury can lead to increased amyloid-beta plaques and neurofibrillary tangles, two of the hallmark signs of AD.

Possible reasons for the link between head injuries and dementia include disruption of neurometabolic processes due to rotational and shearing forces that can damage axons and cause cytoskeletal damage. This can mean progressive cell death and the accumulation of amyloid-beta plaques in the surrounding areas. While the evidence of increased neurofibrillary tangles following a single TBI isn't as clear, case histories of increased tangles being found a year or more following moderate to severe TBI have been documented.

Still, while there does seem to be evidence for increased risk of AD pathology in some individuals with a history of TBI, the actual mechanisms underlying this risk are still poorly understood. To explore this link between TBI and AD pathology further, a new research study published in the journal Neuropsychology examines cases of AD as confirmed by autopsy findings and how they relate to a history of head injuries.

A team of researchers led by C. Munro Cullen of the University of Texas Southwestern Medical Center examined data taken from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) and Neuropathology Data Set (NDS). Both the NACC and NDS collect clinical, autopsy, demographic, and genetic data on people diagnosed with AD or other brain pathologies.

All participants included in the data sets were diagnosed with some form of dementia at one of 32 Alzheimer's disease centers across the United States funded by the National Institute on Aging between September 2005 and March 2015. Each participant was interviewed either alone or with a family member to provide information on medical history and whether they had a history of prior head injuries. Along with an initial diagnosis of Alzheimer's disease given on intake or during follow-up visits, autopsy data was collected after death to confirm the diagnosis.

Of the 2,153 participants with autopsy-confirmed AD examined in the study, 197 reported some form of prior head injury, and participants with no history of head injuries were used as controls. On average, participants reporting a moderate to severe head injury involving loss of consciousness began showing symptoms of dementia three years earlier than participants with no history of TBI. Even when controlling for other factors such as lifetime history of depression, family history of dementia, level of education, and medical history, the link between dementia and TBI remained.

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While similar results have been reported in previous studies, this is the first to use autopsy results to confirm the AD diagnosis. Despite these results, it still remains unclear why head injuries may lead to early dementia in certain individuals. Though some studies suggest that TBI can result in neurological damage, including an increased number Lewy bodies and cerebral microinfarcts, establishing a direct causal link to dementia has proven difficult. Another possibility raised by researchers is that TBI can also reduce cognitive reserve in older adults, making them more vulnerable to developing dementia symptoms.

As C. Munro Cullen and co-authors indicate in discussing their findings, this study did not look at additional factors that may have influenced the results, including the effects of multiple head injuries, how TBI severity was measured, and whether cognitive decline may have begun before the head injury occurred. Also, given that many older adults who sustain head injuries do not develop dementia afterward, there also appear to be protective factors that need to be identified.

Though more research is needed to explore the TBI-dementia link, studies such as this one help demonstrate the potential risks faced by older adults recovering from serious accidents. With the number of patients suffering from Alzheimer's disease and other dementias expected to rise significantly over the next few decades, learning more about potential avenues for prevention and treatment may be one of the most important challenges facing public health today.