CME Author: Vicki Brower
Study Authors: Kristine Yaffe, Sandy J. Lwi, et al.
Target Audience and Goal Statement:
Veterans Administration and civilian neurologists, psychologists, psychiatrists, and internists
The goal of this study was to understand whether diagnoses of traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and depression alone or in combination increase the risk of dementia among older female veterans, and if so, by how much?
Questions Addressed by this Study:
What are the military-related risk factors for dementia among female veterans? Specifically, how do TBI, PTSD, and depression contribute to the development of dementia in female veterans? How does this compare to what is seen in male military veterans?
Study Synopsis and Perspective:
Experts have noted over the past 10 years that military veterans have higher risk than the general population for neuropsychiatric disorders such as TBI, PTSD, and depression. However, most of the research in this field has been conducted in men, not women. With increasing numbers of women joining the military (and serving in combat situations), animal studies that “suggest sex differences in response to TBI and sex differences in the neurobiology of PTSD and depression… it is possible that neuropsychiatric conditions may be differentially associated with dementia risk in men versus in women,” authors wrote. This study addresses this gap in knowledge.
To focus on risks for dementia among female military veterans, Kristine Yaffe, MD, of the University of California San Francisco, and colleagues, reviewed the records of 109,140 female veterans ages ≥55 who received care at a Veterans Health Administration medical center from 2004 to 2015, and who had at least one follow-up visit. Their average age was 68.5; most women (74%) were non-Hispanic whites, and 12% were non-Hispanic blacks.
The researchers determined diagnoses of TBI, PTSD, and depression from ICD-9-CM codes at inpatient and outpatient visits. In the sample, 81,135 women had none of these conditions; 20,410 had depression only, 1,363 had PTSD only, 488 had TBI only, and 5,044 had more than one condition.
At an average follow-up of 4.0 years, 4,125 female veterans (4%) had developed dementia. After adjusting for demographics, socioeconomic status, and medical comorbid conditions, women with TBI, PTSD, and depression were more likely to develop dementia than women without these diagnoses:
- Women who had a TBI: adjusted sub-distribution hazard ratio (which takes into account competing events) (adjusted sHR) 1.49 (95% CI 1.01-2.20)
- Women with PTSD: adjusted sHR 1.78 (95% CI 1.34-2.36)
- Women with depression: adjusted sHR 1.67 (95% CI 1.55-1.80)
- Women with more than one diagnosis had the highest risk for dementia: adjusted sHR 2.15 (95% CI 1.84-2.51)
Female military veterans who had TBI, PTSD, or depression were more likely to develop dementia than female veterans without these conditions, researchers reported.
Moreover, women who had more than one of these military-related risk factors had more than a twofold risk of developing dementia, the authors wrote in Neurology.
The links between TBI and dementia and between PTSD and dementia were similar to ones reported previously for male veterans, but the association between depression and dementia was lower for women than men.
Neurology online Dec. 12, 2018; doi:10.1212/WNL.0000000000006778
Study Highlights: Explanation of Findings
Having a TBI increased dementia risk in female veterans by 50%, while PTSD increased it by almost 80%, and depression increased it by almost 70%, according to the study. This is consistent with recent research in veteran and civilian populations that indicate that TBI increases the risk of developing dementia. The new findings also echo estimates from a prior study the same team conducted of male veterans in which TBI was similarly associated with a 60% increase in the risk of dementia.
“Almost nothing is known about dementia risk in female veterans, and this is the first study that we know of that has attempted to understand their dementia risk,” Yaffe told MedPage Today. “Although the risk factors that we focused on — TBI, PTSD, and depression — are not exclusive to military service, these risk factors are more prevalent in veterans, and PTSD and depression are also more prevalent in women,” Yaffe said.
It has become increasingly apparent that military veterans are at higher risk than the general population for TBI, PTSD, and depression, according to Andrea Schneider, MD, PhD, and Geoffrey Ling, MD, PhD, both of Johns Hopkins University School of Medicine in Baltimore, writing in an accompanying editorial. “More women are joining the military, and there is increasing evidence of sex differences in dementia risk in the general population.”
These risk factors are important to understand as more women take on combat roles, she added, noting that nearly one in three veterans deployed for Operations Enduring Freedom and Iraqi Freedom are estimated to have one of these conditions.
Rates of PTSD are high already among female veterans, and are expected to rise as more women enter the military. Authors of the study acknowledge that the mechanisms connecting PTSD and depression to dementia are not well-defined, “but may include inflammation, high levels of cortisol or other stress markers, and increased vascular disease,” they wrote. “These results highlight the possibility that early and more targeted treatment of PTSD and depression might reduce the risk of developing dementia.”
Yaffe and colleagues pointed out that depression, TBI, and PTSD often co-occur, but few studies have considered the effect of these risk factors together. It is striking then, that in this study almost 80% of women with PTSD also had one of the other conditions, and almost half of women with TBI also had a psychiatric diagnosis. Female veterans who had a combination of military-related risk factors had a dementia risk that increased ≥ 2-fold. This may be the case because of increased neural damage or decreased cognitive reserve, which are common to brain injuries, PTSD, and depression, authors noted. Researchers also pointed out that their findings indicate that PTSD and depression independently increase dementia risk among older female veterans.
They also hypothesized that the link between TBI and risk of dementia may be due to damage to axons, “an injury that reduces cognitive reserve, thereby increasing vulnerability to dementia neuropathology or accelerating production of dementia-related proteins such as beta-amyloid and tau.”
In addition, they note that TBI and dementia have also been linked by other neuropathologic changes, such as white matter degeneration and neuroinflammation.
Finally, the study’s authors pointed out that animal models and human studies indicate that the inflammatory cascade triggered by a TBI may be distinct for men and for women. Specifically, estrogen and progesterone may have neuroprotective effects after a brain injury, they wrote.
“Our findings stress the need for both increased dementia screening in women with these risk factors and for more research on intervention strategies that might modify the effects of these risk factors,” said Yaffe.
Schneider and Ling wrote, “Future studies will need to include both men and women to assess directly for possible interaction by sex in associations between TBI, PTSD, and depression and dementia risk.”
Associations of TBI, PTSD, and depression with incident dementia weakened after accounting for the number of follow-up visits, the researchers noted. Women with one of those diagnoses had two to three times as many visits as women who did not have these diagnoses. This closer follow-up may have resulted in a dementia diagnosis earlier because providers had more opportunities to observe cognitive and functional changes.
The study has other limitations, they added. It relied solely on ICD-9-CM codes to define TBI, PTSD, depression, and dementia, not diagnostic interviews. It’s possible women with less severe symptoms of these disorders did not receive diagnoses and were not counted. The study is observational in nature, and no causal relationships can be determined, Yaffe added.
Judy George wrote the original story for MedPage Today