Sex differences in cognitive decline among middle-aged and older adults: a cohort study in Europe.

OBJECTIVES: Previous studies on sex differences in cognitive decline provide inconsistent findings, with many European countries being underrepresented. We determined the association between sex and cognitive decline in a sample of Europeans and explored differences across birth cohorts and regions. METHODS: Participants 50+ years old enrolled in the Survey of Health, Ageing and Retirement in Europe had their cognition measured by tests of immediate recall, delayed recall and verbal fluency biennially up to 17 years of follow-up (median 6, interquartile range 3-9 years). We used linear mixed-effects models to assess the relationship between sex and the rate of cognitive decline, adjusting for sociodemographic and health-related characteristics. RESULTS: Of 66,670 participants (mean baseline age 63.5 ± standard deviation 9.4), 55% were female. Males and females had similar rates of decline in the whole sample in immediate recall (beta for interaction sex × time B = 0.002, 95% CI -0.001 to 0.006), delayed recall (B = 0.000, 95% CI -0.004 to 0.004), and verbal fluency (B = 0.008, 95% CI -0.005 to 0.020). Females born before World War II had a faster rate of decline in immediate recall and delayed recall compared to males, while females born during or after World War II had a slower rate of decline in immediate recall. Females in Central and Eastern Europe had a slower rate of cognitive decline in delayed recall compared to males. DISCUSSION: Our study does not provide strong evidence of sex differences in cognitive decline among older Europeans. However, we identified heterogeneity across birth cohorts and regions.

Impact of adverse pregnancy outcomes on brain vascular health and cognition.

A State of the Art lecture titled "Impact of Adverse Pregnancy Outcomes on Brain Vascular Health and Cognition" was presented at the International Society on Thrombosis and Haemostasis Congress in 2023. Adverse pregnancy outcomes, encompassing conditions such as gestational hypertension, eclampsia, preeclampsia, preterm birth, fetal growth restriction, stillbirth, and gestational diabetes, may form part of an underrecognized pathway from early adulthood reproductive health factors to later-life vascular cognitive impairment and dementia in women. Adverse pregnancy outcomes are caused by dysregulated vascular and metabolic adaptations during pregnancy, and these pathophysiological changes may persist after delivery. Adverse pregnancy outcomes may contribute to the increased risk of cognitive impairment and dementia directly through vascular and metabolic dysregulation and subsequent development of cardiovascular diseases, or other biological processes may be at play, such as shared maternal risk factors. Extensive epidemiologic evidence has shown that many cognitive impairment and dementia cases may be prevented or delayed by strategies targeting midlife cardiovascular health. Despite the recognized importance of adverse pregnancy outcomes for cardiovascular health, the literature on associated long-term health outcomes is limited. In this State of the Art review article, we summarize the current epidemiologic evidence on the relationship between adverse pregnancy outcomes and cognitive impairment and dementia and provide an overview of the potential pathophysiological mechanisms. Finally, we summarize relevant new data on this topic presented during the 2023 International Society on Thrombosis and Haemostasis Congress.

Educational attainment and anxiety in middle-aged and older Europeans.

We examined the relationship between educational attainment (EA) and anxiety symptoms in a sample of 77,792 individuals (median age = 64 years, 55% female) from the Survey of Health, Ageing and Retirement in Europe. Using logistic regression, we estimated odds ratio (OR) with 95% confidence interval (CI) for the association between EA (7 educational levels based on International Standard Classification of Education) and anxiety symptoms (12 or more points from the shortened 5-item version of the Beck Anxiety Inventory), adjusting for sociodemographic and health-related factors. We further explored whether the relationship varied by region, sex and age group. Independent of sociodemographic and health-related factors, higher levels of EA were associated with lower odds of anxiety symptoms. The magnitude of this association plateaued at first stage of tertiary education (OR 0.40; 95% CI 0.35-0.47, p < 0.001). The association was stronger in females, middle-aged individuals and in Central and Eastern Europe while not apparent in Northern Europe. Our findings suggest that individuals with higher education might be protected against anxiety throughout life. The protective effect of education against anxiety symptoms is more pronounced in less egalitarian regions and in females.

Depression in healthcare workers during COVID-19 pandemic: results from Czech arm of HEROES Study.

The pandemic due to COVID-19 brought new risks for depression of health care workers, which may have differently influenced men and women. We aimed to investigate (1) whether health care workers in Czechia experienced an increase in depression during the COVID-19 pandemic, (2) which factors contributed the most to this change, and (3) whether the magnitude of the associations differed by gender. We studied 2564 participants of the Czech arm of the international COVID-19 HEalth caRe wOrkErS (HEROES) Study. Online questionnaire was administered to health care workers in summer 2020 (wave 0) and spring 2021 (wave 1). Depression was defined by reaching 10 or more points on the Patient Health Questionnaire. Logistic regression investigated the association of participant´s characteristics with depression and multivariable decomposition for non-linear models assessed, to what extent the characteristic explained the change in depression occurrence. The prevalence of depression increased twice during the pandemic (11% in wave 0 and 22% in wave 1). Stress accounted for 50% of the difference, experience of death due to COVID-19 for 15% and contact with COVID-19 patients for 14%. Greater resilience and sufficient personal protective equipment were strongly associated with lower occurrence of depression. The protective association of resilience with depression was stronger in men than in women. We conclude that interventions to promote mental health of health care workers in future health crisis should aim at decreasing stress and enhancing resilience. They should be delivered especially to individuals who have contact with the affected patients and may face their death.

Sons and parental cognition in mid-life and older adulthood.

Prior research suggests a relationship between number of sons and maternal long-term health outcomes, including dementia. We assessed the relationship between having sons and parental cognitive aging. Specifically, we investigated the relationship between having at least 1 son and parental baseline cognition level and rate of cognitive decline, accounting for life course sociodemographic characteristics in a cohort of 13 222 adults aged ≥50 years from the US Health and Retirement Study. We included only participants with at least one child. We further explored whether this relationship varies by parental sex and whether the magnitude of the relationship increases with each additional son. Cognition was assessed biennially for a maximum of nine times as a sum of scores from immediate and delayed 10-noun free recall tests, a serial 7s subtraction test, and a backwards counting test. Associations were evaluated using linear mixed-effects models, stepwise adjusting for sociodemographic and health-related factors. In our analytic sample of parents, a total of 82.3% of respondents had at least 1 son and 61.6% of respondents were female. Parents of at least 1 son had a faster rate of cognitive decline in comparison to parents without any son. Our results also suggest that cognitive decline was faster among parents of multiple sons, compared to parents with only daughters. Thus, the results support the theory that having sons might have a long-term negative effect on parental cognition.

Gender/Sex Differences in the Association of Mild Behavioral Impairment with Cognitive Aging.

BACKGROUND: While the gender/sex differences in neuropsychiatric symptoms in dementia population are well described, gender/sex differences in mild behavioral impairment (MBI) in dementia-free populations and the relationship to cognitive performance and to subsequent cognitive decline have not been studied. OBJECTIVE: We aimed to explore gender/sex differences in the association of MBI with the level of cognitive performance and its rate of decline in a dementia-free cohort. METHODS: We studied 8,181 older adults enrolled in the online PROTECT UK Study. MBI was assessed using the MBI Checklist and cognition was measured by digit span, paired associate learning, spatial working memory, and verbal reasoning. Statistical analysis was conducted using linear regression models and linear mixed-effects models. RESULTS: Out of 8,181 individuals (median age 63 years, 73% females), 11% of females and 14% of males had MBI syndrome. Females exhibited less often symptoms of decreased motivation (45% versus 36% in males), impulse dyscontrol (40% versus 44% in males; p = 0.001) and social inappropriateness (12% versus 15%; p < 0.001), while they showed more often symptoms of emotional dysregulation (45% versus 36%; p < 0.001). The associations of MBI domains with some measures of cognitive performance and decline were stronger in males than females, with the exception of the association of emotional dysregulation with the rate of cognitive decline in verbal reasoning, which was present exclusively in females. CONCLUSION: MBI may influence cognition to a greater extent in males than in females. We propose that predictors and biomarkers of dementia should consider gender/sex as an effect modifier.

Risk and protective factors of neurocognitive disorders in older adults in Central and Eastern Europe: A systematic review of population-based studies.

BACKGROUND: A wide range of potentially modifiable risk factors, indicating that the onset of neurocognitive disorders can be delayed or prevented, have been identified. The region of Central and Eastern Europe has cultural, political and economic specifics that may influence the occurrence of risk factors and their link to the cognitive health of the population. OBJECTIVE: We aimed to systematically review population-based studies from Central and Eastern Europe to gather evidence on risk and protective factors for neurocognitive disorders. METHODS: We searched the electronic databases PubMed, Cochrane Database of Systematic Reviews, PsycINFO, Web of Science, and Embase. The search was performed on 26th of February 2020 and repeated at the end of the review process on 20th May 2021. RESULTS: We included 25 papers in a narrative synthesis of the evidence describing cardiovascular risk factors (n = 7), social factors (n = 5), oxidative stress (n = 2), vitamins (n = 2), genetic factors (n = 2) and other areas (n = 7). We found that there was a good body of evidence on the association between neurocognitive disorders and the history of cardiovascular disease while there were gaps in research of genetic and social risk factors. CONCLUSION: We conclude that the epidemiological evidence from this region is insufficient and population-based prospectively followed cohorts should be established to allow the development of preventive strategies at national levels.

Association Between Season of Birth and Cognitive Aging in Older Adults: Pan-European Population-Based Study on 70,000 Individuals.

BACKGROUND: Several early-life factors have been associated with higher risk of developing dementia. It is unclear whether season of birth (SOB) can affect cognitive aging in older adults or not. OBJECTIVE: We aimed to study the association of SOB with the level of cognitive performance as well as with the rate of cognitive decline. METHODS: We studied 70,203 individuals who participated in the Survey of Health, Aging and Retirement in Europe. Cognition was measured with tests on verbal fluency and immediate and delayed recall. We assessed the association of SOB with the level of cognitive performance using multiple linear regression and with the rate of cognitive decline using linear mixed-effects models. RESULTS: When compared to individuals born in winter and adjusted for sociodemographic and health-related characteristics, being born in summer was associated with a higher level of delayed recall (B 0.05; 95%CI 0.01 to 0.09) and verbal fluency (B 0.15; 95%CI 0.00 to 0.29) and being born in fall with a higher level of immediate recall (B 0.04; 95%CI 0.01 to 0.08) and verbal fluency (B 0.15; 95%CI 0.01 to 0.29). Individuals born in summer had a higher yearly decline in delayed recall (B -0.005; 95%CI -0.009 to 0.000), while the scores in delayed recall in participants born in spring showed an inverse trend (B 0.005; 95%CI 0.000 to 0.010). CONCLUSION: Individuals born in winter seem to carry a life-long disadvantage in a lower level of cognitive performance; however, being born in winter does not seem to affect the rate of cognitive decline.

Role of sex in the association between childhood socioeconomic position and cognitive ageing in later life.

We aimed to explore sex differences in the association of childhood socioeconomic position (SEP) with the level of cognitive performance and the rate of cognitive decline. We studied 84,059 individuals (55% women; mean age 64 years) from the Survey on Health, Ageing and Retirement in Europe. Sex differences in the association of childhood SEP (household characteristics at age 10) with the level of cognitive performance (verbal fluency, immediate recall, delayed recall) were analysed using multilevel linear regression. Structural equation modelling tested education, depressive symptoms and physical state as mediators. The relationship between childhood socioeconomic advantage and disadvantage and the rate of cognitive decline was assessed using linear mixed-effects models. Higher childhood SEP was associated with a higher level of cognitive performance to a greater extent in women (B = 0.122; 95% CI 0.092-0.151) than in men (B = 0.109; 95% CI 0.084-0.135). The strongest mediator was education. Childhood socioeconomic disadvantage was related to a higher rate of decline in delayed recall in both sexes, with a greater association in women. Strategies to prevent impaired late-life cognitive functioning, such as reducing childhood socioeconomic disadvantages and improving education, might have a greater benefit for women.

Trajectories of depressive symptoms and associated patterns of cognitive decline.

The aim was to investigate the pattern and rate of cognitive decline across distinctive trajectories of depressive symptoms in older adults. In this prospective multinational cohort study on 69,066 participants (on average 64 years at baseline, 55% women), assessments of cognitive functions (immediate recall, delayed recall, verbal fluency) and depressive symptoms (EURO-D scale) were conducted at 2-year intervals. The trajectories of depressive symptoms were obtained using latent growth mixture modelling, cognitive decline was assessed using smoothing splines and linear mixed effects models. Four distinct trajectories of depressive symptoms were identified: constantly low (n = 49,660), constantly high (n = 2999), increasing (n = 6828) and decreasing (n = 9579). Individuals with increasing and constantly high depressive symptoms showed linear cognitive decline, while those with constantly low and decreasing depressive symptoms had fluctuating cognition. Participants with increasing depressive symptoms had the fastest decline, while those with decreasing symptoms were spared from decline in cognition. This study suggests that the pattern as well as the rate of cognitive decline co-occurs with specific patterns of changes in depressive symptoms over time. The most pronounced cognitive decline is present in individuals, in whom depressive symptoms increase late in life. Unique mechanisms of cognitive decline may exist for subgroups of the population, and are associated with the trajectory of depressive symptoms.

Changes in depressive symptoms of older adults in the Czech Republic.

BACKGROUND: It is unclear whether the rising burden of depression is due to its increasing prevalence or better detection. We aimed to study trends in depressive symptoms in older individuals from the Czech Republic. METHODS: We used data from the Survey on Health, Aging and Retirement in Europe. Depressive symptoms, defined by 4 or more points on the EURO-D scale, alone or in combination with pharmacological treatment, were compared between participants in 2006/2007 (cohort 1) and in 2015 (cohort 2). Binary logistic regression assessed the association of cohort 2 with depressive symptoms, step-wise adjusting for sociodemographic and clinical covariates. RESULTS: The prevalence of depressive symptoms (defined by EURO-D) was 28% in cohort 1 and 22% in cohort 2 (p < 0.001). Cohort 2 was associated with lower odds of depressive symptoms, adjusting for all covariates (OR 0.77; 95% CI 0.63-0.94). Defined by EURO-D scale or pharmacological treatment, the prevalence was 30% in cohort 1 and 26% in cohort 2 (p < 0.001). Cohort 2 was associated with lower odds of depressive symptoms, adjusting for age and sex, but not in the fully adjusted model (OR 0.88; 95% CI 0.73-1.07). The difference in depressive symptoms between cohorts was associated in particular with increased length of education and higher household net worth. LIMITATIONS: Information about pharmacological treatment has been reported inaccurately. CONCLUSIONS: The prevalence of depressive symptoms has decreased in older adults in the Czech Republic. Additional increase in education and socioeconomic resources of the population could further reduce the depressive symptoms in the population.