Perceived Stress Linked to Cognitive Impairment among Older Adults in the REGARDS Study

An independent association observed between perceived stress and both prevalent and incident cognitive impairment in older adults suggests that regular screening in primary care for signs and symptoms among high-risk patients should become routine for this population, conclude investigators writing in JAMA Network Open.

“Perceived stress is defined as a consequence of events or demands that exceed an individual’s professed ability to cope,” write first author Ambar Kulshreshtha, MD, PhD, associate professor, Department of Family and Preventive Medicine and Department of Epidemiology at Emory University, and colleagues. They cite research demonstrating long-term physiologic and psychological consequences of perceived stress as well as studies that have found the behavioral condition a modifiable risk factor for Alzheimer disease and related dementias.

As preface to their study, Kulshreshtha et al also cite research suggesting that the high prevalence of dementia among racial and ethnic minorities may be linked to excessive stress fomented by social determinants of health.

They call for more in-depth research into potential associations and chose for their research to tap data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a large cohort study comprising a national US sample of non-Hispanic Black and White adults aged ≥45 years, with the former population oversampled.

In addition to evaluating the association between perceived stress and cognitive impairment, the researchers also examined wither race, sex, and age would modify the association.

A total of 30 239 participants were enrolled in REGARDS during recruitment between 2003 and 2007, with ongoing follow-up conducted annually. For the current analysis, participants were included who had data available on cognition, perceived stress, physical activity, substance use, and chronic disease.

The investigators measured perceived stress using the 4-item version of the Cohen Perceived Stress Scale, assessing the measure at the baseline visit and during 1 follow-up visit.

To assess cognitive function, Kulshreshtha and colleagues used the Six-Item Screener (SIS), a brief measure of global cognitive status, with a score <5 indicating cognitive impairment. Incident cognitive impairment was defined as a shift from intact cognition (SIS score >4) at the first assessment to impaired cognition (SIS score 4) at the latest available assessment. Statistical analysis was conducted from May 2021 to March 2022.

FINDINGS

The final cohort for analysis numbered 24 448. Participants had a median age of 64 years, 60% were women, and 41.6% were non-Hispanic Black.

Overall, 22.9% of participants reported elevated levels of stress. In models adjusted for sociodemographic variables, cardiovascular (CV) risk, and depression, higher levels of perceived stress were associated with 1.37 times greater odds of poor cognition (95% CI, 1.22-1.53). Factors associated with increased perceived stress included younger age, female sex, and being Black. CV risk factors were “significantly more frequently observed” in this group.

When the investigators examined the association between a change in the Perceived Stress Scale score from baseline to follow up (dichotomized into low vs high stress) and incident cognitive impairment they found it was statistically significant in both the unadjusted model (OR, 1.62; 95% CI, 1.46-1.8) and after the model was adjusted for sociodemographic factors, CV risk factors, lifestyle factors, and depression (aOR, 1.39; 95% CI, 1.22-1.58). They found no interaction with age, race, and sex.

Additionally, after the model was stratified for sex and race, the association between greater perceived stress and increased cognitive impairment was similar for all demographics, with 1.05 higher odds for Black men and White men and 1.04 higher odds for Black women and White women.

The investigators suggest several explanations for a link between percieved stress and poor health outcomes including aberrant glucocorticoid secretion, alteration in autonomic tone, and an increased risk of unhealthy lifestyle behaviors. Research into the biological pathway has found evidence for an association between elevated levels of stress biomarkers and brain atrophy and cognitive decline.

“Our results from this large cohort of Black and White individuals suggest that there is an independent association between perceived stress and cognition,” they wrote, adding that the magnitude of the association remained consistent after multivarialbe adjustment.

"More research is needed to explore the underlying mechanisms for this observed association and to develop screening programs and targeted interventions to reduce stress among older adults at risk of cognitive impairment," they concluded.

Reference. Kulshreshtha A, Alonso A, McClure LA, Hajjar I, Manly JJ, Judd S. Association of stress with cognitive function among older Black and white US adults. JAMA Netw Open. 2023;6(3):e231860. doi:10.1001/jamanetworkopen.2023.1860