In a recent study published in JAMA Network Open, researchers investigated whether posttraumatic stress disorder (PTSD) symptoms in civilian midlife women negatively affected their cardiovascular and neurocognitive health.

Study: Posttraumatic Stress Disorder Symptoms and Cardiovascular and Brain Health in Women. Image Credit: Prostock-studio/


They conducted a cross-sectional study of American women, incorporating extensive PTSD questionnaires, anthropometric measures, neuropsychological examinations, ultrasonography, and magnetic resonance imaging (MRI).

Their results revealed that the presence and severity of PTSD symptoms were associated with an increased risk of carotid atherosclerosis. Women who also carried the APOEε4 allele presented more significant brain small vessel disease and reduced cognitive performance.

PTSD and its role in health

Posttraumatic stress disorder (PTSD) is a mental health condition triggered by an event or experience that the patient considers terrifying. The condition is characterized by symptoms that include flashbacks, nightmares, and severe anxiety. More often than not, the condition requires clinical and psychological interventions to manage and treat.

Research has found that women are twice as susceptible to PTSD compared to men. This is alarming, given the high prevalence of PTSD-triggering experiences in the world today. Studies have estimated that almost all women in the United States (US) will go through at least one major traumatic event over the course of their lives.

Even worse, recent research suggests that PTSD’s demerits extend beyond just the mental, with growing bodies of evidence alluding to its cardiovascular and neurocognitive impacts.

Cardiovascular disease (CVD) and dementia (especially Alzheimer’s disease [AD]) are major causes of female mortality worldwide. In the US, CVD and AD rank first and fourth, respectively, as leading causes of women’s death.

Prevalence extends beyond mortality risk, with an estimated 45% of all American women suffering from the condition during their lifetime. Understanding the associations between PTSD and CVD/AD would provide medical practitioners and policymakers the information required to implement safeguards, improving overall women’s health.

Unfortunately, most studies on the link between PTSD and health focus on men, with few studies on women and even fewer on midlife women. Midlife represents a crucial period for women. It encompasses menopause, associated with significant hormone disruption independently associated with increased vascular risk, the potential reemergence of prior mental trauma, and decreased memory.

This period further immediately precedes the onset of clinical CVD and coincides with the highest risk of AD development.

Research focusing on the links between cardiovascular and neurological health in midlife women, and the influence of PTSD on both, is essential to identify and combat the drivers of these comorbidities, potentially revealing novel therapies that could reduce the risk of these deadly conditions.

About the study

In the present study, researchers investigated the associations between PTSD symptoms and carotid intima-media thickness (IMT), white matter hyperintensity (WMH), and volume (WMHV). They further evaluated cognition and memory in response to PTSD of varying intensities.

The methodology for the study complied with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations for cross-sectional studies.

The study cohort, titled ‘MsBrain,’ comprised women aged 45 to 67 years who volunteered to enroll in the brain health and menopause study. Participants were recruited between 2017 and 2020 from Pittsburgh, Pennsylvania.

Women who were pregnant, presented bilateral oophorectomy or hysterectomy, or had any history of stroke, Parkinson’s disease, or cerebrovascular accident were excluded. Further exclusion criteria included dementia, cancer, current substance abuse, or the use of hormone modulators.

Of the 664 women screened, 274 met the inclusion criteria and were subjected to study procedures. PTSD symptoms presence and prevalence were measured using the Civilian Version of the PTSD Checklist (PCL-C). Higher scores represented greater PTSD severity, with scores ≥30 representing clinical PTSD cutoff.

Carotid IMT was evaluated using ultrasonography. Four locations, respectively, from the left and right carotid arteries, walls of the distal carotid artery, and the carotid bulb were imaged and categorized using a semiautomated reading software. IMT was defined as the mean of all readings taken.

Brain white matter (WMH and WMHV) was measured using MRI scans. Cerebral and cerebellar white matter were scanned and comprised the case (cerebral) and control (cerebellar) for individual participants.

An in-person neuropsychological examination was conducted for attention and memory performance to measure cognitive health. Cognitive processing speed was evaluated using the Symbol Digit Modalities Test. Visual perception and reaction were assessed with the Findings A’s test. The Montreal Cognitive Assessment was used to assess global cognitive function.

Anthropometric measurements included height, weight, and systolic- and diastolic blood pressure. Sociodemographic variables included race, ethnicity, gender, and education level.

Finally, enzymatic assays were used to compute fasting glucose, cholesterol, triglycerides, insulin, and lipoprotein (HDL and LDL) fasting levels. Linear regression models were used for statistical analyses of generated data.

Study findings

Statistical analyses of the data revealed that, among midlife women in the US, PTSD was associated with CVD and AD risk. Higher PTSD symptom severity was observed to result in greater carotid atherosclerosis, especially in women who were APOEε4 allele carriers.

Furthermore, in these carriers, PTSD symptoms were correlated with globally diminished cognitive performance and increased WMHV (Whole brain, deep cortex, frontal lobe, and periventricular).

The APOEε4 genotype has been associated with increased dementia risk in both men and women, with women presenting higher risk than their male counterparts. In studies focused on men, the allele has been observed to result in elevated CVD and PTSD susceptibility, further compounding the condition.

The current study highlights this allele as being responsible for a greater adverse outcome of prior traumatic experiences in women. It identifies the female cohort at greatest risk from PTSD outcomes.

“We considered PTSD symptoms in association with the regional distribution of WMHV. Women who were APOEε4 carriers who had higher PTSD symptoms had greater whole-brain WMHV, periventricular WMHV, deep WMHV, and WMHV in the frontal lobe. Notably, frontal lobe WMHs have been particularly linked to vascular risk, suggesting the importance of vascular processes here.”


The present study investigates the associations between traumatic experiences in women, and their subsequent risk of neurological and cardiovascular conditions, particularly during the midlife period. The study comprised extensive psychological assessments, cognitive evaluations, MRIs, and ultrasonography.

Linear regression analyses of derived data revealed that PTSD, CVD, and AD are linked, with more severe PTSD symptoms resulting in greater brain damage, poorer global cognitive function, and higher carotid atherosclerosis. Women who were carriers for the APOEε4 allele were identified as the highest-risk cohort, presenting more drastic CVD and AD risk than their non-carried counterparts.

“The findings of this cross-sectional study underscore the important implications of PTSD and its symptoms for women’s cardiovascular and brain health, with women who were APOEε4 carriers particularly at risk. PTSD is a major women’s health issue, affecting 10% of women in their lifetime. Our findings point to an at-risk population that may warrant early intervention and prevention efforts to reduce cardiovascular and neurocognitive risk at midlife and beyond.”