Midlife women who had experienced a traumatic event had higher WMH volumes than women who had not experienced such an event. Of the traumatic experiences assessed, sexual assault was the single trauma significantly related to WMHs. These associations persisted with adjustment for multiple covariates, including key cardiovascular risk factors, objectively-assessed sleep, depressive or post-traumatic symptoms, and even a history of childhood abuse or neglect. Findings point to potential adverse impact of trauma, particularly sexual assault, on women’s brain health.
This study is the first to demonstrate that traumatic events are associated with greater WMHs. Select prior literature has linked traumatic experiences to stroke or dementia, but these studies largely focused on childhood abuse and self-reported outcomes (Kershaw et al., 2014; Kornerup et al., 2010; Merrick et al., 2019; Radford et al., 2017; Rich-Edwards et al., 2012; Scott et al., 2013). This study advances this literature in its use of neuroimaging as well as examination of a broader range of traumatic experiences throughout life. Use of neuroimaging allows for investigation of these relationships among women earlier in life, which supports the identification of at-risk women for early detection and intervention.
A highly novel finding is that sexual assault was the single trauma associated with WMHs. Notably, sexual violence is highly prevalent in the United States (US), with 44% of women having experienced sexual assault in their lifetime (Smith et al., 2018). A limited literature has linked sexual assault to cerebrovascular health, with one study finding a history of sexual assault was associated with increased risk of self-reported stroke (Santaularia et al., 2014), and another finding military sexual assault (sexual assault or repeated, threatening sexual harassment in the context of military service) linked to medical record-documented cerebrovascular disease (Gibson et al., 2020). However, no prior literature has examined sexual assault in relation to WMHs. These data underscore the importance of sexual violence to women’s brain health.
Several mechanisms may link trauma and sexual assault to WMHs. Trauma and sexual assault in particular have been associated with adverse cardiovascular disease (CVD) risk factor profiles (Breiding et al., 2008; Santaularia et al., 2014) that have been linked to WMHs (Debette et al., 2011). However, the associations between trauma and WMHs remained when we controlled for these risk factors. Trauma exposure is often associated with poor sleep, and we and others have found poorer sleep continuity associated with greater volume of WMHs (Thurston et al., 2020). However, control for objectively-assessed sleep did not attenuate these associations. Trauma exposure is a major stressor, which increases the risk for psychiatric disorders such as depression and PTSD (Kessler, Davis, & Kendler, 1997; Liu et al., 2017), yet our associations were not explained by depressive or PTSD symptoms assessed via validated instruments. Further, our findings were not explained by a history of childhood abuse, which has been linked to stroke later in life (Kornerup et al., 2010; Merrick et al., 2019; Rich-Edwards et al., 2012), and can set individuals on a trajectory of increased trauma exposure throughout life (Ullman, Najdowski, & Filipas, 2009). We carefully considered key behavioral factors, particularly alcohol and substance use, as well as an addiction history, which did not explain our associations here. Other mechanisms, such as the hypothalamic pituitary adrenal axis, inflammatory pathways, or epigenetic changes warrant investigation in these relationships.
In additional exploratory analyses, we also considered regional WMHs. We found that trauma was related to significantly greater WMHs in the left and right parietal lobe as well as in the left frontal lobe. When considering individual traumas, findings were most consistent for sexual assault and parietal WMHs. These associations are notable given findings that parietal lobe WMHs in particular predict later incident Alzheimer Disease (Brickman et al., 2012).
It is notable that although sexual assault was the most common trauma reported in this study (23%), the sexual assault prevalence found here is lower than that reported from national surveys (Smith et al., 2018). Reasons for our lower rate may have included our more constrained definition of sexual assault (contact with private parts) as compared to many national surveys which often include additional experiences such as forced kissing (Smith et al., 2018). Further, in light of our exclusion criteria (CVD-free, largely nonsmoking, no SSRI/SNRI antidepressant use), our sample was likely lower risk than the general population.
This work has limitations. Our trauma measure was a checklist that assessed if the trauma occurred but not its timing or chronicity. We also did not have information on the perpetrator of any violence; and thus, intimate partner violence could not be distinguished from other forms of physical or sexual assault. The next steps of this work should include investigating these questions with more detailed multidimensional trauma measures that also include information on the timing, frequency of occurrence, and the relationship of any perpetrators of interpersonal violence to the respondent. Further, statistical power for addressing the impact of traumas that had a low base rate here was limited (e.g., death of child); future work should select populations with level rates of these traumas to ascertain their links to health. We assessed PTSD and depression via validated symptom measures, but not via clinical diagnostic interview, which can be implemented in the next steps of this work. This work only included women; whether results can be extended to those of other genders requires investigation.
This study has key strengths. Considering traumatic experiences and sexual assault in particular in relation to WMH is novel. We considered a range of potential confounders in this work, including key risk factors and psychiatric symptoms. As women are at particular risk for poor brain health as they age, our focus on women adds important information to the growing body of work that investigates midlife women’s brain health.