Psychosocial factors, health behaviors and risk of cancer incidence: Testing interaction and effect modification in an individual participant data meta-analysis.

Depression, anxiety and other psychosocial factors are hypothesized to be involved in cancer development. We examined whether psychosocial factors interact with or modify the effects of health behaviors, such as smoking and alcohol use, in relation to cancer incidence. Two-stage individual participant data meta-analyses were performed based on 22 cohorts of the PSYchosocial factors and CAncer (PSY-CA) study. We examined nine psychosocial factors (depression diagnosis, depression symptoms, anxiety diagnosis, anxiety symptoms, perceived social support, loss events, general distress, neuroticism, relationship status), seven health behaviors/behavior-related factors (smoking, alcohol use, physical activity, body mass index, sedentary behavior, sleep quality, sleep duration) and seven cancer outcomes (overall cancer, smoking-related, alcohol-related, breast, lung, prostate, colorectal). Effects of the psychosocial factor, health behavior and their product term on cancer incidence were estimated using Cox regression. We pooled cohort-specific estimates using multivariate random-effects meta-analyses. Additive and multiplicative interaction/effect modification was examined. This study involved 437,827 participants, 36,961 incident cancer diagnoses, and 4,749,481 person years of follow-up. Out of 744 combinations of psychosocial factors, health behaviors, and cancer outcomes, we found no evidence of interaction. Effect modification was found for some combinations, but there were no clear patterns for any particular factors or outcomes involved. In this first large study to systematically examine potential interaction and effect modification, we found no evidence for psychosocial factors to interact with or modify health behaviors in relation to cancer incidence. The behavioral risk profile for cancer incidence is similar in people with and without psychosocial stress.

The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis.

BACKGROUND: Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). METHODS: Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). RESULTS: Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). CONCLUSIONS: Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

Circulating metabolites modulated by diet are associated with depression.

Metabolome reflects the interplay of genome and exposome at molecular level and thus can provide deep insights into the pathogenesis of a complex disease like major depression. To identify metabolites associated with depression we performed a metabolome-wide association analysis in 13,596 participants from five European population-based cohorts characterized for depression, and circulating metabolites using ultra high-performance liquid chromatography/tandem accurate mass spectrometry (UHPLC/MS/MS) based Metabolon platform. We tested 806 metabolites covering a wide range of biochemical processes including those involved in lipid, amino-acid, energy, carbohydrate, xenobiotic and vitamin metabolism for their association with depression. In a conservative model adjusting for life style factors and cardiovascular and antidepressant medication use we identified 8 metabolites, including 6 novel, significantly associated with depression. In individuals with depression, increased levels of retinol (vitamin A), 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1) (lecithin) and mannitol/sorbitol and lower levels of hippurate, 4-hydroxycoumarin, 2-aminooctanoate (alpha-aminocaprylic acid), 10-undecenoate (11:1n1) (undecylenic acid), 1-linoleoyl-GPA (18:2) (lysophosphatidic acid; LPA 18:2) are observed. These metabolites are either directly food derived or are products of host and gut microbial metabolism of food-derived products. Our Mendelian randomization analysis suggests that low hippurate levels may be in the causal pathway leading towards depression. Our findings highlight putative actionable targets for depression prevention that are easily modifiable through diet interventions.

Sleep and 24-hour activity rhythms and the risk of stroke: a prospective cohort study.

Introduction Short and long self-reported sleep durations are associated with a higher risk of stroke, but the association of objective estimates of sleep and 24-hour activity rhythms is less clear. We studied the association of actigraphy-estimated sleep and 24-hour activity rhythms with the risk of stroke in a population-based cohort of middle-aged and elderly. Methods We included 1718 stroke-free participants (mean age 62.2 ± 9.3 years, 55.1% women) from the prospective, population-based Rotterdam Study. Actigraphy-estimated sleep (total sleep time, sleep efficiency, sleep onset latency and wake after sleep onset) and 24-hour activity rhythms (interdaily stability, intradaily variability and onset of the least active 5 hours) were measured during a median of 7 days (Q1-Q3: 6-7 days). The association of sleep and 24-hour activity rhythms with risk of stroke was analyzed using Cox proportional hazards models. Results During a mean follow-up of 12.2 years (SD: 3.2), 105 participants developed a stroke, of whom 81 had an ischemic event. Although there was no clear association between actigraphy-estimated sleep and the risk of stroke, a more fragmented 24-hour activity rhythm was associated with a higher risk of stroke (hazard ratio [HR] per SD increase 1.28, 95% confidence interval [CI] 1.07-1.53). A less stable (HR per SD increase in stability 0.78, 95%CI 0.63-0.97) and more fragmented (HR 1.28, 95%CI 1.04 - 1.58) 24-hour activity rhythm were also associated with a higher risk of ischemic stroke. Conclusions Disturbed 24-hour activity rhythms, but not sleep, are associated with a higher risk of stroke in middle-aged and elderly persons. This suggests that unstable and fragmented activity rhythms may play a more prominent role in the risk of stroke than sleep per se.

Are some children genetically predisposed to poor sleep? A polygenic risk study in the general population.

BACKGROUND: Twin studies show moderate heritability of sleep traits: 40% for insomnia symptoms and 46% for sleep duration. Genome-wide association studies (GWAS) have identified genetic variants involved in insomnia and sleep duration in adults, but it is unknown whether these variants affect sleep during early development. We assessed whether polygenic risk scores for insomnia (PRS-I) and sleep duration (PRS-SD) affect sleep throughout early childhood to adolescence. METHODS: We included 2,458 children of European ancestry (51% girls). Insomnia-related items of the Child Behavior Checklist were reported by mothers at child's age 1.5, 3, and 6 years. At 10-15 years, the Sleep Disturbance Scale for Children and actigraphy were assessed in a subsample (N = 975). Standardized PRS-I and PRS-SD (higher scores indicate genetic susceptibility for insomnia and longer sleep duration, respectively) were computed at multiple p-value thresholds based on largest GWAS to date. RESULTS: Children with higher PRS-I had more insomnia-related sleep problems between 1.5 and 15 years (BPRS-I < 0.001 = .09, 95% CI: 0.05; 0.14). PRS-SD was not associated with mother-reported sleep problems. A higher PRS-SD was in turn associated with longer actigraphically estimated sleep duration (BPRS-SD < 5e08 = .05, 95% CI: 0.001; 0.09) and more wake after sleep onset (BPRS-SD < 0.005 = .25, 95% CI: 0.04; 0.47) at 10-15 years, but these associations did not survive multiple testing correction. CONCLUSIONS: Children who are genetically predisposed to insomnia have more insomnia-like sleep problems, whereas those who are genetically predisposed to longer sleep have longer sleep duration, but are also more awake during the night in adolescence. This indicates that polygenic risk for sleep traits, based on GWAS in adults, affects sleep already in children.

The Rotterdam Study. Design update and major findings between 2020 and 2024.

The Rotterdam Study is a population-based cohort study, started in 1990 in the district of Ommoord in the city of Rotterdam, the Netherlands, with the aim to describe the prevalence and incidence, unravel the etiology, and identify targets for prediction, prevention or intervention of multifactorial diseases in mid-life and elderly. The study currently includes 17,931 participants (overall response rate 65%), aged 40 years and over, who are examined in-person every 3 to 5 years in a dedicated research facility, and who are followed-up continuously through automated linkage with health care providers, both regionally and nationally. Research within the Rotterdam Study is carried out along two axes. First, research lines are oriented around diseases and clinical conditions, which are reflective of medical specializations. Second, cross-cutting research lines transverse these clinical demarcations allowing for inter- and multidisciplinary research. These research lines generally reflect subdomains within epidemiology. This paper describes recent methodological updates and main findings from each of these research lines. Also, future perspective for coming years highlighted.

Lifetime prevalence and associated factors of itch with skin conditions: Atopic dermatitis, psoriasis and dry skin in individuals aged over 50.

BACKGROUND: Itch, common in dermatological conditions, is often accompanied by psychological distress and reduced quality of life. However, research on the prevalence and associated factors of itch with skin conditions in general populations is limited. OBJECTIVES: This cross-sectional study aimed to determine the lifetime prevalence of itch with skin conditions and identify its associated factors in middle-aged and elderly individuals. METHODS: Participants from the Rotterdam Study, a population-based cohort, were interviewed to assess whether they had ever had an itchy skin condition, defining lifetime itch with skin conditions. Over 20 demographic, lifestyle, dermatological, and non-dermatological factors were collected. Multivariable logistic regression analysis explored associations between these factors and itch with skin conditions, reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: 5,246 eligible participants (age range: 51-100, median age: 67, female: 56.0%) revealed a lifetime prevalence of 33.7% for itch with skin conditions. Female sex (OR (95% CI): 1.26 (1.11-1.43)), body mass index (1.02 (1.01-1.03)), self-reported and presence of atopic dermatitis (4.29 (3.74-4.92), and 1.97 (1.60-2.43)), self-reported and presence of psoriasis (2.31 (1.77-3.01), and 2.11 (1.55-2.87)), self-reported dry skin (1.95 (1.73-2.29)), self-reported asthma (1.40 (1.08-1.83)), renal impairment (1.45 (1.17-1.79)), and clinically relevant depressive and anxiety symptoms (1.85 (1.52-2.25), and 1.36 (1.11-1.66)) were significantly associated with it. CONCLUSIONS: This study reveals a substantial one-third lifetime prevalence of itch with skin conditions in individuals aged over 50. Significant associations with diverse lifestyle, demographic, dermatological and, intriguingly, non-dermatological factors including renal impairment, imply additional contributors to itch induction or persistence in individuals with skin conditions.

Plasma neurofilament light chain in association to late-life depression in the general population.

AIM: Investigating what is underlying late-life depression is becoming increasingly important with the rapidly growing elderly population. Yet, the associations between plasma biomarkers of neuroaxonal damage and late-life depression remain largely unclear. Therefore, we determined cross-sectional and longitudinal associations of neurofilament light chain (NfL) with depression in middle-aged and elderly individuals, and total tau, ß-amyloid 40 and 42 for comparison. METHODS: We included 3,895 participants (71.78 years [SD = 7.37], 53.4% women) from the population-based Rotterdam Study. Between 2002 and 2005, NfL, total tau, ß-amyloid 40 and ß-amyloid 42 were determined in blood and depressive symptoms were measured with the Center for Epidemiologic Studies Depression scale (CES-D). Incident depressive events (clinically relevant depressive symptoms, depressive syndromes, major depressive disorders) were measured prospectively with the Center for Epidemiologic Studies Depression, a clinical interview and follow-up of medical records over a median follow-up of 7.0 years (interquartile range 1.80). We used linear and Cox proportional hazard regression models. RESULTS: Each log2 pg./mL increase in NfL was cross-sectionally associated with more depressive symptoms (adjusted mean difference: 0.32, 95% CI 0.05-0.58), as well as with an increased risk of any incident depressive event over time (hazard ratio: 1.22, 95% CI 1.01-1.47). Further, more amyloid-ß 40 was cross-sectionally associated with more depressive symptoms (adjusted mean difference: 0.70, 95% CI 0.15-1.25). CONCLUSION: Higher levels of NfL are cross-sectionally associated with more depressive symptoms and a higher risk of incident depressive events longitudinally. The association was stronger for NfL compared to other plasma biomarkers, suggesting a potential role of neuroaxonal damage in developing late-life depression.

Depression, anxiety, and the risk of cancer: An individual participant data meta-analysis.

BACKGROUND: Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, prostate, colorectal, alcohol-related, and smoking-related cancers), individual participant data (IPD) meta-analyses were performed within the Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. METHODS: The PSY-CA consortium includes data from 18 cohorts with measures of depression or anxiety (up to N = 319,613; cancer incidences, 25,803; person-years of follow-up, 3,254,714). Both symptoms and a diagnosis of depression and anxiety were examined as predictors of future cancer risk. Two-stage IPD meta-analyses were run, first by using Cox regression models in each cohort (stage 1), and then by aggregating the results in random-effects meta-analyses (stage 2). RESULTS: No associations were found between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers. Depression and anxiety (symptoms and diagnoses) were associated with the incidence of lung cancer and smoking-related cancers (hazard ratios [HRs], 1.06-1.60). However, these associations were substantially attenuated when additionally adjusting for known risk factors including smoking, alcohol use, and body mass index (HRs, 1.04-1.23). CONCLUSIONS: Depression and anxiety are not related to increased risk for most cancer outcomes, except for lung and smoking-related cancers. This study shows that key covariates are likely to explain the relationship between depression, anxiety, and lung and smoking-related cancers. PREREGISTRATION NUMBER: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=157677.

The bidirectional association of 24-h activity rhythms and sleep with depressive symptoms in middle-aged and elderly persons.

BACKGROUND: In older populations disturbed 24-h activity rhythms, poor sleep, and depressive symptoms are often lingering and co-morbid, making treatment difficult. To improve insights into these commonly co-occurring problems, we assessed the bidirectional association of sleep and 24-h activity rhythms with depressive symptoms in middle-aged and elderly persons. METHODS: In 1734 participants (mean age: 62.3 ± 9.3 years, 55% women) from the prospective Rotterdam Study, 24-h activity rhythms and sleep were estimated with actigraphy (mean duration: 146 ± 19.6 h), sleep quality with the Pittsburgh Sleep Quality Index, and depressive symptoms with the Center for Epidemiological Studies Depression scale. Repeated measures were available for 947 participants (54%) over a median follow-up of 6 years (interquartile range = 5.6-6.3). Linear-mixed models were used to assess temporal associations of 24-h activity rhythms and sleep with depressive symptoms in both directions. RESULTS: High 24-h activity rhythm fragmentation (IV) (B = 1.002, 95% confidence interval (CI) = 0.641-1.363), long time in bed (TIB) (B = 0.111, 95% CI = 0.053-0.169), low sleep efficiency (SE) (B = -0.015, 95% CI = -0.020 to -0.009), long sleep onset latency (SOL) (B = 0.009, 95% CI = 0.006-0.012), and low self-rated sleep quality (B = 0.112, 95% CI = 0.0992-0.124) at baseline were associated with increasing depressive symptoms over time. Conversely, more depressive symptoms at baseline were associated with an increasing 24-h activity rhythm fragmentation (B = 0.002, 95% CI = 0.001-0.003) and TIB (B = 0.009, 95% CI = 0.004-0.015), and a decreasing SE (B = -0.140, 95% CI = -0.196 to -0.084), SOL (B = 0.013, 95% CI = 0.008-0.018), and self-rated sleep quality (B = 0.193, 95% CI = 0.171-0.215) over time. CONCLUSION: This study demonstrates a bidirectional association of 24-h activity rhythms, actigraphy-estimated sleep, and self-rated sleep quality with depressive symptoms over a time frame of multiple years in middle-aged and elderly persons.

Associations of neuroimaging markers with depressive symptoms over time in middle-aged and elderly persons.

BACKGROUND: Cerebrovascular disease is regarded as a potential cause of late-life depression. Yet, evidence for associations of neuroimaging markers of vascular brain disease with depressive symptoms is inconclusive. We examined the associations of neuroimaging markers and depressive symptoms in a large population-based study of middle-aged and elderly persons over time. METHODS: A total of 4943 participants (mean age = 64.6 ± 11.1 years, 55.7% women) from the Rotterdam Study were included. At baseline, total brain volume, gray matter volume, white matter volume, white matter hyperintensities volume, cortical infarcts, lacunar infarcts, microbleeds, white matter fractional anisotropy, and mean diffusivity (MD) were measured with a brain MRI (1.5T). Depressive symptoms were assessed twice with the Center for Epidemiologic Studies Depression scale (median follow-up time: 5.5 years, IQR = 0.9). To assess temporal associations of neuroimaging markers and depressive symptoms, linear mixed models were used. RESULTS: A smaller total brain volume (ß = -0.107, 95% CI -0.192 to -0.022), larger white matter hyperintensities volume (ß = 0.047, 95% CI 0.010-0.084), presence of cortical infarcts (ß = 0.194, 95% CI 0.047-0.341), and higher MD levels (ß = 0.060, 95% CI 0.022-0.098) were cross-sectionally associated with more depressive symptoms. Longitudinal analyses showed that small total brain volume (ß = -0.091, 95% CI -0.167 to -0.015) and presence of cortical infarcts (ß = 0.168, 95% CI 0.022-0.314) were associated with increasing depressive symptoms over time. After stratification on age, effect sizes were more pronounced at older ages. CONCLUSIONS: Neuroimaging markers of white matter microstructural damage were associated with depressive symptoms longitudinally in this study of middle-aged and elderly persons. These associations were more pronounced at older ages, providing evidence for the role of white matter structure in late-life depressive symptomatology.

Fetal and infant growth patterns, sleep, and 24-h activity rhythms: a population-based prospective cohort study in school-age children.

The study objective was to explore associations of fetal and infant weight patterns and preterm birth with sleep and 24-h activity rhythm parameters at school-age. In our prospective population-based study, 1327 children were followed from birth to age 10-15 years. Fetal weight was estimated using ultrasound in the second and third trimester of pregnancy. Birth weight and gestational age were available from midwife registries. Infant weight was measured at 6, 12 and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change of >0.67 standard deviation between the corresponding age intervals. At school-age, sleep duration, sleep efficiency, wake after sleep onset, social jetlag, inter-daily stability, and intra-daily variability were assessed using tri-axial wrist actigraphy for 9 consecutive nights. We observed that low birth weight (<2500 g) was associated with 0.24 standard deviation (95% confidence interval [CI] 0.04; 0.43) longer sleep duration compared to normal weight. Compared to normal growth, growth deceleration in fetal life and infancy was associated with 0.40 standard deviation (95% CI 0.07; 0.73) longer sleep duration, 0.44 standard deviation (95% CI 0.14; 0.73) higher sleep efficiency, and -0.41 standard deviation (95% CI -0.76; -0.07) shorter wake after sleep onset. A pattern of normal fetal growth followed by infant growth acceleration was associated with -0.40 standard deviation (95% CI -0.61; -0.19) lower inter-daily stability. Preterm birth was not associated with any sleep or 24-h rhythm parameters. Our findings showed that children with fetal and infant growth restriction had longer and more efficient sleep at school-age, which may be indicative of an increased need for sleep for maturational processes and development after a difficult start in life.

The Cross-Sectional Association Between Tinnitus and Actigraphy-Estimated Sleep in a Population-Based Cohort of Middle-Aged and Elderly Persons.

OBJECTIVES: Tinnitus is a common and burdensome disease, often accompanied by complaints of poor sleep. However, associations of tinnitus with objective estimates of sleep remain unclear, particularly in the general population. We assessed these associations in a population-based cohort of middle-aged and elderly persons. DESIGN: This study included 1456 participants (mean age: 65.0 ± 7.1 years, 52% women) from the population-based Rotterdam Study. Tinnitus was self-reported and in those who reported tinnitus daily, symptom severity was assessed with the Tinnitus Handicap Inventory. We used actigraphy to estimate sleep and 24-hour activity rhythms objectively and sleep diaries to assess self-reported sleep. We estimated the difference in sleep and 24-hour activity rhythms first between those with and those without tinnitus and secondly with tinnitus severity. RESULTS: Tinnitus, reported by 341 (23%) participants, and tinnitus severity, assessed in 194 participants with daily tinnitus, were not associated with actigraphy-estimated sleep or 24-hour activity rhythms, but were associated with a longer self-reported sleep onset latency (adjusted difference tinnitus = 2.36, 95% confidence interval [CI] = 0.95-3.78, adjusted difference tinnitus severity = 0.27, 95% CI = 0.013-0.54). After stratification for hearing loss, tinnitus was associated with longer self-reported sleep onset latency (adjusted difference = 2.26, 95% CI = 0.98-3.53) and less stable 24-hour activity rhythms (adjusted difference = -0.02, 95% CI = -0.04 to -0.00) in those with hearing loss. In those without hearing loss, tinnitus was associated with more stable rhythms (adjusted difference = 0.03, 95% CI = 0.01-0.05). CONCLUSIONS: Having tinnitus is associated with a longer self-reported sleep onset latency, but not with objective estimates of sleep, suggesting that the subjective experience of sleep may be particularly disturbed in those with tinnitus. In addition, hearing loss may modify the association of tinnitus and 24-hour activity rhythms.

Sex-specific patterns and lifetime risk of multimorbidity in the general population: a 23-year prospective cohort study.

BACKGROUND: Multimorbidity poses a major challenge for care coordination. However, data on what non-communicable diseases lead to multimorbidity, and whether the lifetime risk differs between men and women are lacking. We determined sex-specific differences in multimorbidity patterns and estimated sex-specific lifetime risk of multimorbidity in the general population. METHODS: We followed 6,094 participants from the Rotterdam Study aged 45 years and older for the occurrence of ten diseases (cancer, coronary heart disease, stroke, chronic obstructive pulmonary disease, depression, diabetes, dementia, asthma, heart failure, parkinsonism). We visualised participants' trajectories from a single disease to multimorbidity and the most frequent combinations of diseases. We calculated sex-specific lifetime risk of multimorbidity, considering multimorbidity involving only somatic diseases (1) affecting the same organ system, (2) affecting different organ systems, and (3) multimorbidity involving depression. RESULTS: Over the follow-up period (1993-2016, median years of follow-up 9.2), we observed 6334 disease events. Of the study population, 10.3% had three or more diseases, and 27.9% had two or more diseases. The most frequent pair of co-occurring diseases among men was COPD and cancer (12.5% of participants with multimorbidity), the most frequent pair of diseases among women was depression and dementia (14.9%). The lifetime risk of multimorbidity was similar among men (66.0%, 95% CI: 63.2-68.8%) and women (65.1%, 95% CI: 62.5-67.7%), yet the risk of multimorbidity with depression was higher for women (30.9%, 95% CI: 28.4-33.5%, vs. 17.5%, 95% CI: 15.2-20.1%). The risk of multimorbidity with two diseases affecting the same organ is relatively low for both sexes (4.2% (95% CI: 3.2-5.5%) for men and 4.5% (95% CI: 3.5-5.7%) for women). CONCLUSIONS: Two thirds of people over 45 will develop multimorbidity in their remaining lifetime, with women at nearly double the risk of multimorbidity involving depression than men. These findings call for programmes of integrated care to consider sex-specific differences to ensure men and women are served equally.

The multidimensionality of sleep in population-based samples: a narrative review.

The identification of optimal sleep duration recommendations for the general population has long been an important goal on the public health agenda, as both short and long sleep duration have been linked to unfavourable health outcomes. Yet, sleep is more than duration alone and can be described across multiple domains, such as timing, regularity, satisfaction, alertness, and efficiency. We reviewed observational population-based studies that examined differences in age, sex, and origin across multiple dimensions of sleep. Reviewed literature suggests an increasing prevalence of insomnia symptoms, shorter and less deep sleep in old age. Overall, women report poorer sleep quality than men despite objective measures revealing shorter and more fragmented sleep in men. Minorities generally have poorer quantity and quality of sleep, but multi-ethnic studies have reported mixed results regarding the subjective experience of sleep. In sum, effects of age, sex and origin differ across sleep dimensions, thereby suggesting that the multidimensionality of sleep and how these different aspects interact should be studied across individuals. Studies should include both self-reported measures and objective assessments in diverse population-based samples, as both aspects are important to understand sleep health in the general population. Data-driven descriptions could provide researchers and clinicians with insights into how well individuals are sleeping and offer concrete targets for promotion of sleep health across the population.

Sleep and perivascular spaces in the middle-aged and elderly population.

Sleep has been hypothesised to facilitate waste clearance from the brain. We aimed to determine whether sleep is associated with perivascular spaces on brain magnetic resonance imaging (MRI), a potential marker of impaired brain waste clearance, in a population-based cohort of middle-aged and elderly people. In 559 participants (mean [SD] age 62 [6] years, 52% women) from the population-based Rotterdam Study, we measured total sleep time, sleep onset latency, wake after sleep onset and sleep efficiency with actigraphy and polysomnography. Perivascular space load was determined with brain MRI in four regions (centrum semiovale, basal ganglia, hippocampus, and midbrain) via a validated machine learning algorithm using T2-weighted MR images. Associations between sleep characteristics and perivascular space load were analysed with zero-inflated negative binomial regression models adjusted for various confounders. We found that higher actigraphy-estimated sleep efficiency was associated with a higher perivascular space load in the centrum semiovale (odds ratio 1.10, 95% confidence interval 1.04-1.16, p = 0.0008). No other actigraphic or polysomnographic sleep characteristics were associated with perivascular space load in other brain regions. We conclude that, contrary to our hypothesis, associations of sleep with perivascular space load in this middle-aged and elderly population remained limited to an association of a high actigraphy-estimated sleep efficiency with a higher perivascular space load in the centrum semiovale.

Child mental health problems as a risk factor for academic underachievement: A multi-informant, population-based study.

OBJECTIVE: To investigate whether child mental health problems prospectively associate with IQ-achievement discrepancy (i.e., academic under- and over-achievement) in emerging adolescence. The secondary aims were to test whether these associations are specific to certain mental health problems, to assess potential sex differences, and to examine whether associations are robustly observed across multiple informants (i.e., maternal and teacher-reports). METHODS: This study included 1,577 children from the population-based birth cohort the Generation R Study. Child mental health problems at age 6 were assessed by mothers and teachers using the Child Behavior Checklist and the Teacher's Report Form. The IQ-achievement discrepancy was quantified as the standardized residuals of academic achievement regressed on IQ, where IQ was measured with four tasks from the Wechsler Intelligence Scale for Children-Fifth Edition around age 13 and academic attainment was measured with the Cito test, a national Dutch academic test, at the end of elementary school (12 years of age). RESULTS: Mental health problems at age 6 were associated with IQ-achievement discrepancy at age 12, with more problems associating with greater academic underachievement. When examining specific mental health problems, we found that attention problems was the only mental health problem to independently associate with the IQ-achievement discrepancy (adjusted standardized difference per 1-standard deviation, mother: -0.11, p < 0.001, 95% CI [-0.16, -0.06]; teacher: -0.13, p < 0.001, 95% CI [-0.18, -0.08]). These associations remained after adjusting for co-occurring mental health problems. The overall pattern of associations was consistent across boys and girls and across informants. CONCLUSION: Mental health problems during the transition from kindergarten to elementary school associate with academic underachievement at the end of elementary school. These associations were primarily driven by attention problems, as rated by both mothers and teachers-suggesting that strategies targeting attention problems may be a particularly promising avenue for improving educational performance irrespective of IQ, although this should be established more thoroughly through further research.

The association of early life stress with IQ-achievement discrepancy in children: A population-based study.

Early life stress (ELS) is associated with lower IQ and academic achievement; however, it remains unclear whether it additionally explains their discrepancy. In 2,401 children (54% girls, 30.2% migration background) from the population-based study Generation R Study, latent factors of prenatal and postnatal (age 0-10) ELS were estimated, and IQ-achievement discrepancy (age 12) was quantified as variance in academic achievement not explained by IQ. ELS was prospectively associated with larger IQ-achievement discrepancy (ßprenatal  = -0.24; ßpostnatal  = -0.28), lower IQ (ßprenatal  = -0.20; ßpostnatal  = -0.22), and lower academic achievement (ßprenatal  = -0.31; ßpostnatal  = -0.36). Associations were stronger for latent ELS than for specific ELS domains. Results point to ELS as a potential prevention target to improve academic potential.

Determinants of social health trajectories during the COVID-19 pandemic in older adults: the Rotterdam Study.

OBJECTIVES: The coronavirus disease-2019 (COVID-19) pandemic and accompanying lockdown restrictions impacted social life significantly. We studied associations of sociodemographic factors, mental and social health markers, and brain structure with social health trajectories during the COVID-19 pandemic. DESIGN: Prospective longitudinal population-based cohort study. SETTING: Community-dwelling inhabitants of Rotterdam, the Netherlands. PARTICIPANTS: Repeated questionnaires including questions on social health were sent to Rotterdam Study participants from April 2020 onwards. Social health data at study baseline were available for 5017 participants (mean age: 68.7 ± 11.3; 56.9% women). MEASUREMENTS: Determinants were assessed in routine Rotterdam Study follow-up (1990-2020), including global brain volumes in a subset of participants (N = 1720). We applied linear mixed models and generalized estimating equations to quantify associations between determinants and trajectories of loneliness, perceived social isolation and social connectedness over three time points from April 22nd to July 31st 2020. RESULTS: Loneliness prevalence was 27.9% in April 2020 versus 12.6% prepandemic. Social isolation (baseline mean 4.7 ± 2.4) and loneliness scores (baseline mean 4.9 ± 1.5) decreased over time, whereas social connectedness trajectories remained stable. Depressive symptoms, female sex, prepandemic loneliness, living alone, and not owning a pet were independently associated with lower social connectedness and higher social isolation and loneliness at COVID-19 baseline, but recovery of social health was similar for all determinants. Larger intracranial volume was associated with higher social connectedness. CONCLUSIONS: Despite baseline differences for specific determinants, older adults showed similar recovery of loneliness and social isolation alongside stable social connectedness over time during the pandemic. Social health is multidimensional, especially during a global health crisis.

The network of psychosocial health in middle-aged and older adults during the first COVID-19 lockdown.

PURPOSE: Psychosocial health problems, such as social isolation, loneliness, depression and anxiety, have gained attention during the COVID-19 pandemic and are commonly co-occurring. We investigated the network of psychosocial health constructs during the COVID-19 pandemic. METHODS: This study included 4553 participants (mean age: 68.6 ± 11.2 years, 56% women) from the prospective Rotterdam Study, who filled out a questionnaire between April and July 2020, the time of the first COVID-19 wave in the Netherlands. Psychosocial health constructs included were depressive symptoms (Center for Epidemiological Studies Depression scale), anxiety symptoms (Hospital Anxiety and Depression scale), loneliness (University of California, Los Angeles loneliness scale), social connectedness (five items) and pandemic-related worry (five items). We estimated mixed graphical models to assess the network of items of these constructs and whether age and sex affected the network structure. RESULTS: Within the network of psychosocial constructs, a higher depressive symptoms score was particularly associated with items of loneliness and social connectedness, whereas overall anxiety was particularly associated with items of pandemic-related worry. Between people from different sex and age, the network structure significantly altered. CONCLUSION: This study demonstrates that within the same network of psychosocial health constructs, depressive symptom score is particularly associated with loneliness and social connectedness, whereas anxiety symptom score is associated with pandemic-related worry during the first COVID-19 lockdown. Our results support that psychosocial constructs should be considered in conjunction with one another in prevention and treatment efforts in clinical care, and that these efforts need to be tailored to specific demographic groups.