Influence of Perceived Stress on Incident Amnestic Mild Cognitive Impairment

Katz, Mindy J.; Derby, Carol A.; Wang, Cuiling; Sliwinski, Martin J.; Dolatabadi, Jafar Ezzati Nazhad; Zimmerman, Molly E.; Zwerling, Jessica; Lipton, Richard B.

doi:10.1097/wad.0000000000000125

Cited by 58 publications

(40 citation statements)

References 47 publications

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“…The PSS was added to the EAS battery in 2006 and was since been administered at annual evaluations. Other papers using this data have been published [3,5,10]. EAS participants received no monetary compensation, however, they were given lunch as compensation for their time.…”

Section: Methodsmentioning

confidence: 99%

“…One of the most frequently used measures of perceived stress is Cohen’s Perceived Stress Scale (PSS) [2]. High scores on the PSS have been associated with a variety of adverse outcomes including but not limited to cognitive decline [3], depression [4], pain [5] and poor wound healing [6]. The PSS a 14-item questionnaire that evaluates perceived stress over the last four weeks and is made up of seven positively worded questions (PSS-PW) and seven negatively worded questions (PSS-NW).…”

Section: Introductionmentioning

confidence: 99%

“…Even though a two factor solution has been consistently found in the literature, the total PSS score is used in the vast majority of studies to evaluate perceived stress in both younger and older adults [1,3,7,9,10]. Though many studies reporting modest correlations between the PSS subscales, very few have evaluated the subscales of the PSS separately [11,12,13,14,15].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, stress is an important area of study because stress has been linked to cognitive decline in older adults [3]. Dementia is a major cause of morbidity and mortality in older adults [22] and amnestic Mild Cognitive Impairment (aMCI) is a transition state between normal cognition and dementia [23].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore it is important to help clarify the role of stress in the development of aMCI. In a prior study, higher PSS scores were associated with an increased risk of developing aMCI [3]. However, the subscales of the PSS were not tested.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Reliability, Validity, and Predictive Validity of the Subscales of the Perceived Stress Scale in Older Adults

Jiang

Seng

Zimmerman

et al. 2017

JAD

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Background The Perceived Stress Scale (PSS) is made up of two subscales but is typically used as a single summary measure. However, research has shown that the two subscales may have differential properties in older adults. Objective To evaluate the internal consistency, test-retest reliability, and the concurrent and predictive validity for development of aMCI of the positively-worded (PSS-PW) and negatively-worded (PSS-NW) subscale scores of the PSS in older adults. Methods We recruited community residing older adults free of dementia from the Einstein Aging Study. Reliability of the PSS-PW and PSS-NW was assessed using Cronbach’s alpha for internal consistency and intraclass correlation for one year test-retest reliability. Concurrent validity was evaluated by examining the relationship between the PSS subscales and depression, anxiety, neuroticism, and positive and negative affect. Predictive validity was assessed using multivariate Cox regression analyses to examine the relationship between baseline PSS-PW and PSS-NW score and subsequent onset of aMCI. Results Both PSS-PW and PSS-NW showed adequate internal consistency and retest reliabilities. Both the PSS-PW and PSS-NW were associated with depression, neuroticism, and negative affect. The PSS-NW was uniquely associated with anxiety while the PSS-PW was uniquely associated with positive affect. Only the PSS-PW was associated with a statistically significant increased risk of incident aMCI (HR=1.27; 95% CI: 1.06–1.51 for every 5 point increase in PSS-PW). Conclusions Evaluating the separate effects of the two PSS subscales may reveal more information than simply using a single summation score. Future research should investigate the PSS-PW and PSS-NW as separate subscales.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Reliability, Validity, and Predictive Validity of the Subscales of the Perceived Stress Scale in Older Adults

Jiang

Seng

Zimmerman

et al. 2017

JAD

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Association of Stress With Cognitive Function Among Older Black and White US Adults

et al. 2023

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ImportancePerceived stress can have long-term physiological and psychological consequences and has shown to be a modifiable risk factor for Alzheimer disease and related dementias.ObjectiveTo investigate the association between perceived stress and cognitive impairment in a large cohort study of Black and White participants aged 45 years or older.Design, Setting, and ParticipantsThe Reasons for Geographic and Racial Differences in Stroke (REGARDS) study is a national population-based cohort of 30 239 Black and White participants aged 45 years or older, sampled from the US population. Participants were recruited from 2003 to 2007, with ongoing annual follow-up. Data were collected by telephone, self-administered questionnaires, and an in-home examination. Statistical analysis was performed from May 2021 to March 2022.ExposuresPerceived stress was measured using the 4-item version of the Cohen Perceived Stress Scale. It was assessed at the baseline visit and during 1 follow-up visit.Main Outcomes and MeasuresCognitive function was assessed with the Six-Item Screener (SIS); participants with a score below 5 were considered to have cognitive impairment. Incident cognitive impairment was defined as a shift from intact cognition (SIS score &gt;4) at the first assessment to impaired cognition (SIS score ≤4) at the latest available assessment.ResultsThe final analytical sample included 24 448 participants (14 646 women [59.9%]; median age, 64 years [range, 45-98 years]; 10 177 Black participants [41.6%] and 14 271 White participants [58.4%]). A total of 5589 participants (22.9%) reported elevated levels of stress. Elevated levels of perceived stress (dichotomized as low stress vs elevated stress) were associated with 1.37 times higher odds of poor cognition after adjustment for sociodemographic variables, cardiovascular risk factors, and depression (adjusted odds ratio [AOR], 1.37; 95% CI, 1.22-1.53). The association of the change in the Perceived Stress Scale score with incident cognitive impairment was significant in both the unadjusted model (OR, 1.62; 95% CI, 1.46-1.80) and after adjustment for sociodemographic variables, cardiovascular risk factors, and depression (AOR, 1.39; 95% CI, 1.22-1.58). There was no interaction with age, race, and sex.Conclusions and RelevanceThis study suggests that there is an independent association between perceived stress and both prevalent and incident cognitive impairment. The findings suggest the need for regular screening and targeted interventions for stress among older adults.

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Key Roles of CACNA1C/Cav1.2 and CALB1/Calbindin in Prefrontal Neurons Altered in Cognitive Disorders

Datta,

Yang,

Joyce

et al. 2024

JAMA Psychiatry

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ImportanceThe risk of mental disorders is consistently associated with variants in CACNA1C (L-type calcium channel Cav1.2) but it is not known why these channels are critical to cognition, and whether they affect the layer III pyramidal cells in the dorsolateral prefrontal cortex that are especially vulnerable in cognitive disorders.ObjectiveTo examine the molecular mechanisms expressed in layer III pyramidal cells in primate dorsolateral prefrontal cortices.Design, Setting, and ParticipantsThe design included transcriptomic analyses from human and macaque dorsolateral prefrontal cortex, and connectivity, protein expression, physiology, and cognitive behavior in macaques. The research was performed in academic laboratories at Yale, Harvard, Princeton, and the University of Pittsburgh. As dorsolateral prefrontal cortex only exists in primates, the work evaluated humans and macaques.Main Outcomes and MeasuresOutcome measures included transcriptomic signatures of human and macaque pyramidal cells, protein expression and interactions in layer III macaque pyramidal cells using light and electron microscopy, changes in neuronal firing during spatial working memory, and working memory performance following pharmacological treatments.ResultsLayer III pyramidal cells in dorsolateral prefrontal cortex coexpress a constellation of calcium-related proteins, delineated by CALB1 (calbindin), and high levels of CACNA1C (Cav1.2), GRIN2B (NMDA receptor GluN2B), and KCNN3 (SK3 potassium channel), concentrated in dendritic spines near the calcium-storing smooth endoplasmic reticulum. L-type calcium channels influenced neuronal firing needed for working memory, where either blockade or increased drive by β1-adrenoceptors, reduced neuronal firing by a mean (SD) 37.3% (5.5%) or 40% (6.3%), respectively, the latter via SK potassium channel opening. An L-type calcium channel blocker or β1-adrenoceptor antagonist protected working memory from stress.Conclusions and RelevanceThe layer III pyramidal cells in the dorsolateral prefrontal cortex especially vulnerable in cognitive disorders differentially express calbindin and a constellation of calcium-related proteins including L-type calcium channels Cav1.2 (CACNA1C), GluN2B-NMDA receptors (GRIN2B), and SK3 potassium channels (KCNN3), which influence memory-related neuronal firing. The finding that either inadequate or excessive L-type calcium channel activation reduced neuronal firing explains why either loss- or gain-of-function variants in CACNA1C were associated with increased risk of cognitive disorders. The selective expression of calbindin in these pyramidal cells highlights the importance of regulatory mechanisms in neurons with high calcium signaling, consistent with Alzheimer tau pathology emerging when calbindin is lost with age and/or inflammation.

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Influence of Perceived Stress on Incident Amnestic Mild Cognitive Impairment

Cited by 58 publications

References 47 publications

Evaluation of the Reliability, Validity, and Predictive Validity of the Subscales of the Perceived Stress Scale in Older Adults

Evaluation of the Reliability, Validity, and Predictive Validity of the Subscales of the Perceived Stress Scale in Older Adults

Association of Stress With Cognitive Function Among Older Black and White US Adults

Key Roles of CACNA1C/Cav1.2 and CALB1/Calbindin in Prefrontal Neurons Altered in Cognitive Disorders

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