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Post-traumatic stress disorder (PTSD) could have adverse effects on the cardiovascular and brain health of women in midlife, particularly for those with a certain genetic makeup.

Women with higher PTSD symptoms had significantly greater carotid atherosclerosis, according to research published in JAMA Network Open.

PTSD also affected neurocognitive health among carriers of the APOEε4 genotype, which has previously been linked with Alzheimer’s disease.

APOEε4 carriers with higher PTSD symptoms had greater brain white matter hyperintensities, which is an indicator of brain small vessel disease,  as well as poorer cognition.

“PTSD is a major women’s health issue, affecting 10% of women in their lifetime,” the researchers reported.

“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.”

The cross-sectional MsBrain study included 274 women living in Pittsburgh, Pennsylvania, who were aged between 45 and 67 years without a history of cardiovascular disease, stroke or dementia.

Participants were enrolled between 2016 and 2021 and underwent screening procedures, physical measurements, a medical history interview, phlebotomy, neuropsychological testing, carotid artery ultrasonography, and brain magnetic resonance imaging.

All completed a PTSD questionnaire, which was a validated, 17-item, self-report inventory assessing PTSD symptoms over the past month.

Overall, 24.71% were APOEε4 genotype carriers.

Women with greater PTSD symptoms had a higher carotid intima-media thickness, which was used as an indicator of carotid atherosclerosis. This association was unaffected by  APOEε4 status.

In addition, interactions between PTSD symptoms and APOEε4 status were seen for the primary outcome of whole-brain white matter hyperintensity volume (WMHV).

Among women with APOEε4, the researchers found that PTSD symptoms were also associated with greater, periventricular WMHV, deep WMHV, and frontal WMH.

PTSD symptoms were also associated with poorer cognition among the APOEε4 carriers in multivariable models, specifically relating to attention and working memory, semantic fluency, perceptual speed, and processing speed.

Rebecca Thurston, PhD, from the University of Pittsburgh, and colleagues noted that PTSD symptoms have previously been associated with altered emotion processing and neural circuitry implicated in cognition and stressor-induced cardiovascular reactivity.

They suggested that other potential pathways for the association include inflammatory, autonomic, hypothalamic pituitary adrenal, or epigenetic processes, which also warrant future consideration.

“In our study, APOEε4 genotype was an important modifier of associations of PTSD with neurocognitive outcomes but not carotid atherosclerosis, perhaps due to the greater potency of the APOEε4 genotype in neurocognitive risk,” they added.

“Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health.”

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