Traumatic Brain Injury Ups Dementia Risk in Older Adults

Megan Brooks

November 04, 2014

Adults in their mid-50s and older who sustain a traumatic brain injury (TBI) from a fall or other mishap are at increased risk for dementia, a new study hints.

"I hope that these results will highlight the critical importance of preventing falls in older adults," first author Raquel C. Gardner, MD, from the San Francisco Veterans Affairs Medical Center in California, told Medscape Medical News. "Fall prevention will not only prevent bodily injury but may even help prevent dementia," she said.

Their study was published online October 27 in JAMA Neurology.

More than 60% of all hospital admissions for TBI are in people aged 55 years and older, according to the Centers for Disease Control and Prevention, the researchers write. The highest rates of TBI-related emergency department visits, inpatient visits, and deaths are among people 75 and older.

Prior studies looking at a possible link between a single TBI and the risk for dementia have yielded conflicting results, and most have not included patients with non-TBI trauma (NTT) as controls, the study team says.

Dr Gardner and colleagues quantified the risk for dementia in adults with recent TBI compared with adults with NTT.

Using a California administrative health database, they identified 164,661 patients aged 55 and older diagnosed with TBI or NTT in 2005 or 2006 who were free of dementia at baseline. The cohort included 51,799 (31.5%) patients with TBI and 112,862 (68.5%) with NTT. Falls were the cause of trauma for roughly two thirds of patients overall.

During follow-up lasting 5 to 7 years, 4361 (8.4%) patients with TBI developed dementia, compared with 6610 (5.9%) patients with NTT (P < .001). The average time from trauma to dementia diagnosis was 3.2 years and was shorter in the TBI group than the NTT group (3.1 vs 3.3 years; P < .001).

In the unadjusted model, TBI was significantly associated with dementia diagnosis, with a hazard ratio (HR) of 1.46 (95% confidence interval [CI], 1.41 - 1.52 P < .001).

TBI remained significantly associated with dementia diagnosis in the final model adjusted for all covariates (fully adjusted HR, 1.26; 95% CI, 1.21 - 1.32; P < .001).

A significant interaction was found between TBI severity and age category, such that moderate to severe TBI was associated with increased risk for dementia across all ages. The HR for dementia was 1.72 (95% CI, 1.40 - 2.10; P < .001) at age 55 to 64 years and 1.46 (95% CI, 1.30 - 1.64; P < .001) at age 65 to 74 years.

Mild TBI was a "relatively more important" risk factor for dementia with increasing age, the investigators say. With mild TBI, the HR for dementia was 1.11 (95% CI, 0.80 - 1.53; P = .55) at age 55 to 64 years and 1.25 (95% CI, 1.04 - 1.51; P = .02) at age 65 to 74 years.

There are several major theories regarding the mechanism linking TBI and dementia, the investigators say. TBI may trigger a progressive neurodegenerative cascade, accelerate an established neurodegenerative cascade, or result in a static brain injury that reduces cognitive reserve.

"Given the relatively short duration of follow-up in this study (5-7 years), we are unable to comment on a possible role of TBI in triggering a de novo neurodegenerative cascade, but our results could theoretically lend support to either of the other 2 proposed theories," they note in their article.

"Whether a person with TBI recovers cognitively or develops dementia, however, is likely dependent on multiple additional risk and protective factors, ranging from genetics and medical comorbidities to environmental exposures and specific characteristics of the TBI itself," they point out.

Going forward, "we really need to figure out the underlying mechanisms and the underlying biology of dementia after TBI. Once we figure this out, we will have a shot at developing treatments and cures," Dr Gardner told Medscape Medical News.

Vulnerable Brain

In a linked editorial, Steven T. DeKosky, MD, from the University of Pittsburgh School of Medicine in Pennsylvania, says the finding that TBI increases risk for dementia more than nonbrain trauma itself is "important and speaks to the vulnerability of the aging brain."

"The known structural damage to the brain after TBI, notably of diffuse axonal injury and disruption of neural circuitry, would surely impair function of an older brain and reduce cognitive reserve, as pointed out by Gardner et al. It is likely that the increased emergence of dementia over the ensuing years was due in part to this structural damage and lessened cognitive reserve, leading more quickly to clinical manifestations and a diagnosis of dementia," Dr DeKosky says.

"Unfortunately," he notes, "there was not a nontrauma control group included, which may have answered the question of whether NTT (ie, body trauma itself) raised the risk of dementia significantly above age-equivalent controls without nonbrain trauma (perhaps from inflammation or other complications)."

The study received no commercial funding. The authors and Dr DeKosky have disclosed no relevant financial relationships.

JAMA Neurol. Published online October 27, 2014. Abstract Editorial


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