Posttraumatic stress disorder (PTSD) is associated with accelerated cognitive decline over time, new research suggests.
In an analysis of more than 12,000 middle-aged women who had experienced at least one trauma in their lives, those with PTSD symptoms showed an approximately two-fold faster decline in cognition during follow-up compared with those who did not have PTSD symptoms.
These associations were not fully explained by other known cognition-related factors such as depression, the researchers note.
“PTSD may increase the risk of dementia by accelerating cognitive decline at midlife,” coinvestigator Jiaxuan Liu, MPH, a doctoral candidate at the Harvard TH Chan School of Public Health, Boston, Massachusetts, told Medscape Medical News.
“Our findings may suggest the value of earlier cognitive screening among individuals with PTSD and the importance of PTSD prevention and treatment across the lifespan,” she added.
The results were published online June 30 in JAMA Network Open.
Vital Public Health Issue
“Cognitive decline at midlife and older is of vital public health interest,” Liu said. “It is a risk factor for a variety of poor health outcomes and strongly predicts Alzheimer’s disease and other dementias.”
Although PTSD has been linked to lower cognitive function and dementia incidence, it has not been known whether it is associated with decline in cognitive function, she added.
“In addition, both PTSD and dementia are more common in women than men, so it’s important to understand a possible link,” Liu said.
Because no large-scale study had examined whether PTSD is associated with cognitive decline in women, the current researchers examined PTSD symptoms and their association with repeated measures of cognitive function among a large civilian trauma-exposed cohort of women aged 50 to 70 years at study baseline.
Participants were drawn from the Nurses’ Health Study II: a longitudinal study of a cohort of 116,429 US female nurses who were between 25 and 42 years old at enrollment in 1989. Participants completed biennial questionnaires, with follow-up on an ongoing basis.
The current analysis included 12,270 trauma-exposed women (mean age at baseline, 61.1 years) who completed assessments every 1 or 12 months for up to 24 months after baseline. The mean follow-up time was 0.9 years.
In the study population, 95.9% were non-Hispanic White, 1.3% were Hispanic, 1% were Asian, 0.6% were Black, and 1.2% were classified as “other.”
Higher Depression Scores
Lifetime trauma exposure and PTSD symptoms were assessed from March 1, 2008, to February 28, 2010, using the Short Screening Scale for DSM-IV PTSD.
In total, 67% of the participants reported experiencing PTSD symptoms. The women were divided into four groups, on the basis of symptom number:
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No PTSD symptoms (n = 4052)
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1-3 PTSD symptoms (n = 5058)
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4-5 PTSD symptoms (n = 2018)
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6-7 PTSD symptoms (n = 1052)
The Cogstate Brief Battery, a validated and self-administered online cognitive assessment, was completed by participants between October 3, 2014, and July 30, 2019. The researchers measured cognitive function with two composite scores: psychomotor speed and attention, and learning and working memory.
Covariates potentially associated with cognitive decline included demographic, educational, and behavior-related health factors such as body mass index, physical activity, cigarette smoking, diet quality, and alcohol consumption.
The researchers additionally conducted secondary analyses that adjusted for symptoms and history of depression as well as the consequences of potential practice effects of taking the test multiple times.
Behavior-related health factors “did not substantially differ by PTSD symptom level,” the investigators note. However, compared with women who did not have PTSD symptoms, those who had such symptoms had higher depressive symptom scores and higher rates of clinician-diagnosed depression.
Both cognitive composite scores improved through the follow-up period, “likely because of practice effects,” the researchers write. But after adjusting for practice effects, they found a decline over time in both composite scores.
Dose-Related Trajectories
Results showed that having more PTSD symptoms was associated with dose-related poorer cognitive trajectories.
After adjusting for demographic characteristics, women with the highest symptom level (6-7 symptoms) had a significantly worse rate of change in both composite domains of learning and working memory (β = −0.08 SD/y; 95% CI, −0.11 to −0.04 SD/y; P < .001) and of psychomotor speed and attention (β = −0.05 SD/y; 95% CI, −0.09 to −0.01 SD/y; P = .02) compared with women with no PTSD symptoms.
Women with four to five PTSD symptoms showed a worse rate of change in learning and working memory compared with those who had no symptoms, but not in psychomotor speed and attention. Women with one to three PTSD symptoms had similar cognitive scores to those of women without PTSD symptoms.
Notably, the associations of PTSD with cognitive change remained evident after additional adjustment for behavioral factors and health conditions — and were only “partially attenuated but still evident” after further adjustment for practice effects and comorbid depression, the investigators write.
“We thought PTSD might be associated with worse cognitive decline through health behaviors like smoking and alcohol drinking and higher risk of other health conditions like hypertension and depression,” Liu said.
However, those factors did not account for the current study’s findings, she noted.
“We could not determine why women with PTSD had faster cognitive decline than those without PTSD,” she said.
Liu suggested that PTSD “may have effects on the brain, such as altering brain structures and affecting brain immune function.” However, more research is needed “to investigate these mechanisms that might underlie the association we found between PTSD and cognitive decline,” she said.
Neurotoxic Effect
Commenting for Medscape Medical News, Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said, “It is well known that stress is neurotoxic, and PTSD is a particularly serious form of stress.”
Fillit is also a clinical professor of geriatric medicine and palliative care, medicine, and neuroscience, Mount Sinai Hospital, New York, and was not involved with the study.
“We tend to think of PTSD in post-acute settings, such as soldiers returning from war,” he said. “This study contributes to our understanding of the long-term effects of PTSD on cognitive decline, measured objectively over time”
Fillit noted that an important implication is that, by increasing the risk for cognitive decline, PTSD also increases risk for Alzheimer’s disease. This leads to the “main take-home, which is that PTSD is a risk factor not only for cognitive decline but also for Alzheimer’s and related dementias,” he said.
However, this opens a potential therapeutic approach, Fillit added.
Because cortisol and other stress hormones drive the stress response, finding ways to block the neurotoxic effects of these hormones “might be a target to prevent cognitive decline and decrease Alzheimer’s disease risk,” he said.
JAMA Netw Open. Published online June 30, 2022. Full text
The study was supported by grants from the National Institute of Mental Health and the National Institutes of Health. Liu reports no relevant financial relationships. The other investigators’ disclosures are listed in the original paper. Fillit reports no relevant financial relationships.
Batya Swift Yasgur MA, LSW, is a freelance writer with a counseling practice in Teaneck, NJ. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom(the memoir of two brave Afghan sisters who told her their story).
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