Women May Have Worse Outcomes After a Brain Injury Than Men

Traumatic brain injury (TBI) is a major cause of disability and death in the U.S., leading to over 223,000 hospitalizations in 2019 and over 64,000 deaths in 2020. Recent findings indicate that your sex may impact the effects of TBI on cognitive function and responsiveness to treatment. Unfortunately, some of these sex differences increase women's risk for dementia.

What does TBI do to the brain?

TBI often is caused by a blow or bump to the head, for example, from falling down the stairs, or from a car accident. Generally speaking, TBIs damage the white matter in the brain, which is important for communication between different brain parts. TBIs also can lead to loss of consciousness, hematomas (pooling of blood in the brain tissue), brain swelling, and skull fractures. Symptoms vary depending on which brain area was affected, as well as the severity of the TBI. Fortunately, 80 percent of reported TBIs are considered to be of mild severity.

Differences in outcomes

Many studies show that women have poorer outcomes than men, such as experiencing more severe or more frequent headaches, depression, short-term memory complaints, sleep problems, and anxiety than men. Dr. Maheen Adamson, Director of Research at the VA national Women’s Operational Military Exposure Network (WOMEN) and professor of neurosurgery at Stanford, is one of the foremost scientists studying how and why female veterans' experience of TBI differs from that of male veterans. She and her team have found that among female and male veterans with TBI, women experienced more psychiatric problems and more vertigo, and even though they tended to have more years of education than male veterans, they were more likely to be unemployed and to be living alone.

Impact of brain injury on the thickness of the brain cortex

Source: Adamson lab/Stanford

In the first study to closely match female and male veterans on key variables such as the severity of TBI, years since TBI, and current age, Dr. Adamson's team found that female veterans had substantial decreases in cortical thickness, which was then correlated with poorer performance on some cognitive tests. Male veterans, on the other hand, showed negligible reductions in cortical thickness. Other studies also have found that decreased cortical thickness is associated with impaired cognitive function and increased risk for dementia.

Due to a confluence of factors, women with TBI may have a higher risk for dementia. First, TBI increases the risk of dementia even when a TBI occurred over 30 years ago. The greater cognitive impairment and reduced cortical thickness that some women experience after a TBI may increase this risk even more. Second, women frequently report experiencing depression after TBI; depression increases the odds of dementia by 1.5 to 2.6 times. Given that age is the biggest risk factor for dementia, the probability of dementia among older women with TBIs may be even greater.

Dr. Adamson worries about the effect of TBI on women veterans' dementia risk. "Cognitive impairment and dementia are also devastating outcomes of TBI. A history of moderate TBI confers a greater than twofold risk of developing Alzheimer's disease." The significant increase in the active-duty female military in recent years is likely to correspond with a proliferation of female combat-related injuries. Her findings "outline a perfect storm of physical brain injury, depression, and astounding financial, psychological, and societal impacts that will lead to a tsunami of dementia among women veterans."

Differences in treatment response

Because TBI symptoms can vary widely from one person to the next, a personalized combination of treatments is typically prescribed. Treatments can include medication, surgery, and rehabilitation. Dr. Adamson's group uses neuromodulation to improve cognitive function, in which nerve cells in the brain are stimulated. She finds that women tend to need more sessions of neuromodulation than men to achieve similar levels of improvement.

This finding may stem from men being overrepresented in clinical studies assessing the utility of these treatments. One review paper found that 80 percent of clinical studies for a particular type of neuromodulation called transcranial magnetic stimulation only included male participants. As Dr. Adamson put it, "if you start with methods that are developed on men, they are going to work better in men."

Why are there sex differences with TBI?

Dr. Helen Bramlett, Professor of Neurological Surgery at the University of Miami Miller School of Medicine, thinks that "hormone fluctuation is one of the root causes" for sex differences in TBI outcomes. She and her colleagues recently wrote a comprehensive review article that described how TBI might impact women differently at each life stage due to the presence or absence of hormones. "You can divide the female lifespan into several very distinct parts based on the fluctuation of hormones or the level of hormones at a particular stage. The levels of hormones change as one moves from adolescence to pregnancy, in some cases, post-pregnancy, perimenopause, menopause, and post-menopause. The levels of hormones that are present during a TBI may influence how well a person does after the TBI." For example, women who have recently completed menopause, who typically are in their 50s, have significantly better outcomes after TBI than women in the perimenopause stage, who tend to be in their 40s.

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What women should do after experiencing a TBI

To reduce the impact on dementia risk, Dr. Adamson recommends lifestyle activities, such as regular exercise, a healthy diet, and stress management. Because there has been a male bias in the clinical treatments developed so far, she also recommends "asking your doctor if their recommended treatment has been demonstrated to be effective for women."

Summary

Women's experience of TBI, from outcome to treatment responsiveness, is distinct from that of men and may increase their risk for dementia. While the underrepresentation of women in TBI studies, particularly in clinical trials, is dispiriting, Dr. Bramlett remains optimistic, "I do think there's become more awareness in needing to make sure that the research you are conducting covers both males and females. If you don't, you're not only doing a disservice to women but to yourself as a scientist."