Caroline Cassels

July 18, 2011

July 18, 2011 (Paris, France) — Traumatic brain injury (TBI), whether mild, moderate, or severe, has been linked to a doubling of dementia risk, new research suggests.

Presented here at the Alzheimer's Association International Conference (AAIC) 2011, results of a large, retrospective cohort study of older veterans showed that compared with individuals with no TBI, the risk for incident dementia over 7 years in those with any TBI diagnosis was more than double and was significant for all TBI types.

"The bottom line is that older veterans with TBI were twice as likely to develop dementia over the 7-year study," principal investigator Kristine Yaffe, MD, professor of psychiatry and epidemiology, University of California, San Francisco, and director of the Memory Disorders Program at the San Francisco Veterans Affairs Medical Center, told reporters attending a press briefing here.

"[The findings] suggest TBI may predispose people to earlier manifestation of [dementia] symptoms and raises hope that treatment or rehabilitation may have a role in preventing downstream dementia," she added.

Dr. Kristine Yaffe

The relationship between TBI and dementia risk is controversial, with some studies suggesting it confers risk and others reporting no risk. Given the large number of soldiers experiencing TBI as part of the current conflicts in Iraq and Afghanistan, Dr. Yaffe noted that clarifying the association between TBI and dementia is important for this cohort. However, she added, it may also have significant implications for the general population.

The Centers of Disease Control and Prevention estimates that approximately 1.7 million TBI-related deaths, hospitalizations, and emergency department visits occur in the United States every year.

Independent Risk Factor

The study included 281,540 U.S. veterans aged 55 years or older who had a least 1 inpatient or outpatient visit during both the baseline period (1997 to 2000) and the follow-up period (2001 to 2007). None of the participants had dementia at baseline.

International Classification of Diseases, 9th revision, codes documented in the participants' medical records were used to determine the presence of TBI diagnoses during baseline and dementia diagnoses during follow-up, and also to ascertain medical and psychiatric comorbid conditions.

A total of 4902 (1.7%) of the total cohort had a baseline TBI diagnosis. Veterans had a mean age of 67 years, and 4% were women.

The most common diagnosis was intracranial injury, which accounted for 40% of TBI diagnoses. This was followed by unspecified head injury (34%), concussion (15%), postconcussion syndrome (12%), and skull fracture (5%). In addition, more than 1 diagnosis was noted in 6% of participants.

The unadjusted risk for dementia was more than double in those with TBI compared with those with no TBI, at 15% vs 7%, respectively. The adjusted hazard ratio for incident dementia in those with any TBI diagnosis was 2.6 (95% confidence interval, 2.4 - 2.8).

Furthermore, the association was similar for all TBI diagnoses and was independent of comorbid medical and psychiatric conditions, including post-traumatic stress disorder which, previous research by Dr. Yaffe and colleagues has shown, is also an independent risk factor for dementia.

Potential Mechanisms

According to Dr. Yaffe, several potential mechanisms have been proposed to explain the link between TBI and dementia. The most plausible, she said, is that TBI is associated with diffuse axonal injury or swelling of the axons that form connections between the neurons, which disrupts neuronal communication.

Another "intriguing possibility," said Dr. Yaffe, is that those TBI increases the risk of developing tau tangles and β-amyloid plaques, the signature pathologic hallmark of AD. She noted that these plaques are present in up to 30% of patients with TBI who die acutely after TBI, including children.

It is also possible that over the longer term, axonal degeneration may occur, even after a single TBI, which could lead to earlier manifestation of symptoms. Persistent inflammation or cytoskeletal pathologic abnormalities may also play a role, she said.

Overall, she said, the study has implications for returning veterans as well as the general population.

Clinicians need to recognize TBI as a major risk factor, and individuals who have sustained a head injury constitute a group that should "probably be followed very carefully as they age and be screened for dementia and other cognitive problems," she said.

"Ideally when we have preventative strategies this would be a very good group to offer prevention to," she added.

The study also has potential public health implications and highlights the importance of protecting the skull and brain and conducting research to determine whether optimal treatment of TBI may help prevent "downstream dementia."

Viable Way to Reduce Risk

William Thies, PhD, chief medical and scientific officer at the Alzheimer's Association, said he believes the study's findings are "reasonably generalizable."

Dr. William Thies

The only proviso, he said, is that the cohort was about 95% male, which is "a bit of a limitation."

"That noted, I think in fact that these findings do suggest that protection from head injury is a viable way to minimize your risk of dementia," Dr. Thies told Medscape Medical News.

Dr. Thies added that public awareness of the importance of preventing TBI has grown considerably over the past decade and is reflected in stringent seatbelt laws and greater use of bicycle helmets in adults as well as children.

"One area where I think more should be done is preventing falls in the home, which is a significant issue."

Dr. Thies added that although there is still no proof that TBI causes dementia, this study provides a "strong indicator" that the two are linked.

Dr. Yaffe and Dr. Thies have disclosed no relevant financial relationships.

Alzheimer's Association International Conference (AAIC). P2-117. Presented July 18, 2011.

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