by Todd Neale

Older U.S. veterans with post-traumatic stress disorder (PTSD) appear to have an increased risk of developing dementia, a retrospective study showed.

Compared with those without PTSD, predominantly male veterans with the disorder had a 1.77-fold (95% CI 1.70 to 1.85) greater risk of developing dementia, according to Kristine Yaffe, MD, of the San Francisco Veterans Affairs Medical Center and the University of California San Francisco, and colleagues.

The results were similar when veterans with a history of head injury, substance abuse, and clinical depression were excluded, the researchers reported in the June issue of Archives of General Psychiatry.

“It is important that those with PTSD are treated, and further investigation is needed to see whether successful treatment of PTSD may reduce the risk of adverse health outcomes, including dementia,” Yaffe and her colleagues wrote.

“In addition, it is critical to follow up patients with PTSD, especially if they are of an advanced age, to screen for cognitive impairment.”

PTSD is common among U.S. veterans, affecting an estimated 17% of soldiers returning from Iraq and Afghanistan. The disorder can persist for decades.

There is some evidence of a link between PTSD and impaired cognition, although little is known about PTSD’s potential as a risk factor for dementia.

Yaffe and her colleagues explored the possibility using the Department of Veterans Affairs National Patient Care Database.

They identified 181,093 veterans ages 55 and older (mean age 68.8) who were free from dementia at baseline — 53,155 had PTSD and 127,938 did not.

The vast majority (96.5%) were men.

Through a median follow-up of 7.2 years, 10.6% of veterans with PTSD and 6.6% of those without the disorder were diagnosed with dementia (P<0.001).

After adjustment for demographics and medical and neuropsychiatric comorbidities, the presence of PTSD was associated with an elevated risk for all dementia subtypes, with hazard ratios ranging from 1.71 for Alzheimer’s disease to 2.19 for frontotemporal dementia.

“Mechanisms linking PTSD and dementia must be identified in hope of finding ways to improve the care and outcomes of patients with PTSD,” the researchers wrote.

They offered several possible mechanisms linking the two conditions, including worse cognitive function among veterans with PTSD.

“This poorer performance on cognitive testing compared with those without PTSD could be a risk factor for development of dementia because those with worse function may have less cognitive reserve and be at higher risk for cognitive impairment,” the researchers wrote.

In addition, chronic stress may damage or shrink the hippocampus, which is important in memory and learning. If PTSD leads to hippocampal atrophy, this, in turn, may increase risks of cognitive deficits and dementia.

Additional potential mechanisms include alterations in the hypothalamic-pituitary-adrenal axis, proinflammatory cytokines, or homocysteine levels or other vascular risk factors, all of which may be associated with dementia.

“Finally, it may be that having PTSD, or other chronic brain disorders, may predispose patients to developing dementia because of an increased nonspecific vulnerability — for example, genetic vulnerabilities shared by both disorders or childhood environmental factors,” Yaffe and her colleagues wrote.

They acknowledged some limitations of the study, including the use of diagnostic codes to establish the presence of PTSD, dementia, and other conditions, and the fact that the study participants were primarily male veterans. Thus, the results may not be generalizable to women or those treated elsewhere.

Todd Neale is a MedPage Today staff writer.

Originally published in MedPage Today. Visit MedPageToday.com for more psychiatry news.