Stress Disorders and Dementia in the Danish Population

Gradus, Jaimie L.; Horváth‐Puhó, Erzsébet; Lash, Timothy L.; Ehrenstein, Véra; Tamang, Suzanne; Adler, Nancy E.; Milstein, Arnold; Glymour, M. Maria; Henderson, Victor W.; Sørensen, Henrik Toft

doi:10.1093/aje/kwy269

Cited by 26 publications

(37 citation statements)

References 26 publications

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“…Recently, evidence was also provided for an association between all stressrelated disorders and risk of dementia. 101 However, less is known about the relationship between stress-related disorders and other neurodegenerative diseases. However, PTSD 102 103 and adjustment disorder 104 were shown to be associated with an increased PD risk, whereas stress-related disorders were not found to be associated with ALS risk, 105 but this is clearly under explored.…”

Section: Stress-related Disordersmentioning

confidence: 99%

“…Our finding that individuals with a stress-related disorder were at an increased risk of developing a neurodegenerative disease gains support from previous studies. 95-102 104 However, most of the previous research has focused solely on PTSD 95-100 102 and dementia, [96][97][98][99][100][101] and were often derived from studies of male veterans, who differ significantly from the general population and in terms of trauma exposure. [95][96][97][98] For specific neurodegenerative diseases, we found a statistically significant association for AD but not for PD or ALS.…”

Section: Stress-related Disordersmentioning

confidence: 99%

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Association of Stress-Related Disorders With Subsequent Neurodegenerative Diseases

et al. 2020

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The objective of this thesis was to investigate the relationship of personality and stress with subsequent risk of Parkinson's disease (PD). In Study I, we conducted a population-based cohort study using questionnaire data from the Swedish Twin Registry to explore whether the personality traits, neuroticism and introversion, were associated with later PD risk. We also explored the role of smoking as a mediator in the relationship between personality and PD. Both neuroticism and introversion were associated with an increased PD risk. Further, smoking was a significant mediator in the relationship between personality traits and PD that partly accounted for the effect of introversion, whereas it acted as a suppressor for the effect of neuroticism on PD risk. In Study II, we wanted to further explore the main findings from study I, with the aim to examine whether the observed associations between neuroticism, smoking and PD may be causal. We conducted a two-sample Mendelian randomization study in a network framework, consisting of three main analyses: (I) causal effect of neuroticism on PD, (II) causal effect of neuroticism on smoking initiation, (III) causal effect of smoking initiation on PD. We found no support for a causal association between neuroticism and PD risk. On the other hand, the results indicated that the association between neuroticism and smoking initiation is causal and that there is a strong causal effect of smoking initiation on a reduced PD risk.

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Section: Stress-related Disordersmentioning

confidence: 99%

Section: Stress-related Disordersmentioning

confidence: 99%

Association of Stress-Related Disorders With Subsequent Neurodegenerative Diseases

et al. 2020

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“…A recent Danish register-based study found that stress diagnoses among individuals aged ! 40 years was associated with a higher risk of dementia (Gradus et al, 2018). Yet, the authors noted that the validity of their findings was limited by lack of adjustment for confounding by educational level (Gradus et al, 2018).…”

Section: Introductionmentioning

confidence: 97%

“…Indeed, previous studies support an association between self-reported psychological stress and dementia (Islamoska et al, 2019;Johansson et al, 2010;Nabe-Nielsen et al, 2019;Skogen, Bergh, Stewart, Knudsen, & Bjerkeset, 2015), and between clinical diagnoses of stress and dementia (Flatt, Gilsanz, Quesenberry Jr., Albers, & Whitmer, 2018;Gradus et al, 2018;Greenberg et al, 2014;Mawanda, Wallace, McCoy, & Abrams, 2017;Meziab et al, 2014;Qureshi et al, 2010;Rafferty, Cawkill, Stevelink, Greenberg, & Greenberg, 2018;Yaffe et al, 2010). A stress diagnosis denotes severe stress reactions and adjustment disorders as maladaptive responses to severe or continued exposure to stressors (World Health Organization, 2016).…”

Section: Introductionmentioning

confidence: 97%

Stress diagnoses in midlife and risk of dementia: a register-based follow-up study

Islamoska

Hansen

Ishtiak‐Ahmed

et al. 2020

Aging & Mental Health

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Objectives: Previous studies indicated that stress diagnoses increase the risk of dementia. However, previous results may be biased by confounding, reverse causation and misclassification. Therefore, the main aim of this study was to investigate the association between clinically diagnosed stress in midlife and later dementia risk, while addressing limitations of previous studies. Methods: The study population was selected from all individuals in Denmark born 1935-1956. Individuals diagnosed with stress in midlife (aged 37-58 years) were matched (1:5) with individuals without stress diagnoses based on sex and birthdate (N ¼ 103,484). Data were retrieved from national registers. Cox regression models were adjusted for socio-demographic factors and different morbidities. Results: We found a 2.20 (95% CI: 1.93-2.50) times higher rate of dementia among individuals with any stress diagnosis registered in midlife compared with no stress diagnosis. Hazard rate ratios of dementia were 1.73 (95% CI: 1.13-2.65) among individuals with acute stress reactions, 2.37 (95% CI: 2.05-2.74) among individuals with adjustment disorders, and 2.20 (95% CI: 1.73-2.80) among individuals with unspecified stress reactions. Individuals with PTSD and other stress reactions had non-significantly elevated rates of dementia. Adjustment for confounding only slightly attenuated the association, and reverse causation did not appear to bias the results substantially. Conclusion:Our results support the hypothesis that severe stress in midlife is an important risk factor for dementia. This finding emphasizes the importance of identifying and treating severe stress in midlife to reduce potential detrimental consequences for brain health in later life.

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“…Sensitivity analyses compared personality trait relative risks with and without accounting for selection into the analytic sample using Heckman selection models with traits, race, and baseline SES in the selection equation. Additional sensitivity analyses probed the potential result of both random and systematic outcome misclassification using simulation methods 35 similar to those of a prior dementia study 36 with similar design, and they examined whether any adolescent personality trait was a risk factor associated with use of health services where a dementia diagnosis might be rendered.…”

Section: Discussionmentioning

confidence: 99%

Association Between High School Personality Phenotype and Dementia 54 Years Later in Results From a National US Sample

et al. 2020

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IMPORTANCE Personality phenotype has been associated with subsequent dementia in studies of older adults. However, neuropathologic changes often precede cognitive symptoms by many years and may affect personality itself. Therefore, it is unclear whether supposed dementia-prone personality profiles (high neuroticism and low conscientiousness) are true risk factors or merely reflections of preexisting disease.OBJECTIVES To examine whether personality during adolescence-a time when preclinical dementia pathology is unlikely to be present-confers risk of dementia in later life and to test whether associations could be accounted for by health factors in adolescence or differed across socioeconomic status (SES). DESIGN, SETTING, AND PARTICIPANTSCohort study in the United States. Participants were members of Project Talent, a national sample of high school students in 1960. Individuals were identified who received a dementia-associated International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code during any year between 2011 and 2013. The dates of our analysis were March 2018 to May 2019. EXPOSURES Ten personality traits were measured by the 150-item Project Talent Personality Inventory. Socioeconomic status was measured by a composite based on parental educational level, income, occupation, and property ownership. Participants were also surveyed on demographic factors and height and weight.MAIN OUTCOMES AND MEASURES Medicare records were collected, with dementia diagnoses in the period of 2011 to 2013 classified according to the US Centers for Medicare & Medicaid Services ICD-9-based algorithm. Cox proportional hazards regression models estimated the relative risk of dementia based on the 10 personality traits, testing interactions with SES and adjusting for demographic confounders. RESULTSThe sample of 82 232 participants was 50.1% female, with a mean (SD) age of 15.8 (1.7) years at baseline and 69.5 (1.2) years at follow-up. Lower risk of dementia was associated with higher levels of vigor (hazard ratio for 1 SD, 0.93; 95% CI, 0.90-0.97; P < .001). Calm and maturity showed protective associations with later dementia that increased with SES. At 1 SD of SES, calm showed a hazard ratio of 0.89 (95% CI, 0.84-0.95; P < .001 for the interaction) and maturity showed a hazard ratio of 0.90 (95% CI, 0.85-0.96; P = .001 for the interaction). CONCLUSIONS AND RELEVANCEThis study's findings suggest that the adolescent personality traits associated with later-life dementia are similar to those observed in studies of older persons. Moreover, the reduction in dementia risk associated with a calm and mature adolescent phenotype may be greater at higher levels of SES. Personality phenotype may be a true independent risk factor for dementia by age 70 years, preceding it by almost 5 decades and interacting with adolescent socioeconomic conditions.

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Stress Disorders and Dementia in the Danish Population

Cited by 26 publications

References 26 publications

Association of Stress-Related Disorders With Subsequent Neurodegenerative Diseases

Association of Stress-Related Disorders With Subsequent Neurodegenerative Diseases

Stress diagnoses in midlife and risk of dementia: a register-based follow-up study

Association Between High School Personality Phenotype and Dementia 54 Years Later in Results From a National US Sample

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