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Dispositional optimism is a potentially modifiable factor and has been associated with multiple physical health outcomes, but its relationship with depression, especially later in life, remains unclear. In the Nurses´ Health Study (n = 33,483), we examined associations between dispositional optimism and depression risk in women aged 57–85 (mean = 69.9, SD = 6.8), with 4,051 cases of incident depression and 10 years of follow-up (2004–2014). We defined depression as either having a physician/clinician-diagnosed depression, or regularly using antidepressants, or the presence of severe depressive symptoms using validated self-reported scales. Age- and multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) across optimism quartiles and for a 1-standard deviation (SD) increment of the optimism score. In sensitivity analyses we explored more restrictive definitions of depression, potential mediators, and moderators. In multivariable-adjusted models, women with greater optimism (top vs. bottom quartile) had a 27% (95%CI = 19–34%) lower risk of depression. Every 1-SD increase in the optimism score was associated with a 15% (95%CI = 12–18%) lower depression risk. When applying a more restrictive definition for clinical depression, the association was considerably attenuated (every 1-SD increase in the optimism score was associated with a 6% (95%CI = 2–10%-) lower depression risk. Stratified analyses by baseline depressive symptoms, age, race, and birth region revealed comparable estimates, while mediators (emotional support, social network size, healthy lifestyle), when combined, explained approximately 10% of the optimism-depression association. As social and behavioral factors only explained a small proportion of the association, future research should investigate other potential pathways, such as coping strategies, that may relate optimism to depression risk.

Background: To clarify the mechanisms underlying physical activity (PA)-related cardioprotection, we examined the association of PA with plasma bioactive lipids (BALs) and cardiovascular disease (CVD) events. We additionally performed genome-wide associations. Methods: PA-bioactive lipid associations were examined in VITAL (VITamin D and OmegA-3 TriaL)-clinical translational science center (REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01169259; N=1032) and validated in JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin)-NC (REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00239681; N=589), using linear models adjusted for age, sex, race, low-density lipoprotein-cholesterol, total-C, and smoking. Significant BALs were carried over to examine associations with incident CVD in 2 nested CVD case-control studies: VITAL-CVD (741 case-control pairs) and JUPITER-CVD (415 case-control pairs; validation). Results: We detected 145 PA-bioactive lipid validated associations (false discovery rate Conclusions: We identified a PA-related bioactive lipidome profile out of which 12 BALs also had opposite associations with incident CVD events.

Objectives:Among older people with cognitive impairment and mild dementia, relatively little is known about the factors that predict preferences for everyday living activities and experiences and that influence the relative importance of those activities and experiences.Design:Cross-sectional study.Setting:Participants were recruited from the Massachusetts Alzheimer’s Disease Research Center (MADRC) Clinical Core longitudinal cohort.Participants:The sample included 62 community-dwelling older adults with cognitive impairment (Clinical Dementia Rating global score ≥ 0.5).Measurements:We used the Preferences for Everyday Living Inventory (PELI) to assess preferences for activities and lifestyle experiences among persons with cognitive impairment. Within-subjects analysis of variance was used to test for significant differences in the mean ratings of importance for four domains of the PELI (“autonomous choice,” “social engagement,” “personal growth,” and “keeping a routine”). Multiple regression models were used to relate predictors, including neuropsychiatric symptoms, to importance ratings for each domain.Results:Significant differences were noted in the mean importance ratings of the preferences domains: “social engagement” preferences were rated as most important, followed by “autonomous choice,” “personal growth,” and “keeping a routine.” For the “social engagement” preferences domain, female sex was significantly associated with higher importance of “social engagement,” while depressive symptoms (Geriatric Depression Scale-15 scores) were significantly associated with lower importance.Conclusions:This study adds novel insight into the everyday preferences of community-dwelling older adults with cognitive impairment and highlights the impact of a number of factors, particularly level of depression, on how important various everyday experiences are perceived.

Objective As cognitive impairment progresses, people with dementia increasingly rely on surrogate decision-makers for everyday activities. Yet, little is known about concordance on everyday preferences between persons with cognitive impairment and their care partners. Methods The sample included 69 dyads of persons with cognitive impairment (Clinical Dementia Rating Scale ≥0.5) and their care partners. We used the Preferences for Everyday Living Inventory (PELI) to assess preferences for activities and lifestyle choices among persons with cognitive impairment. The PELI was concurrently but separately administered to care partners, who answered as surrogate decision-makers. Factor analysis was used to ascertain factor structure of the PELI; reliability measures were computed within the sample. Paired sample t-tests were used to estimate differences in scores of corresponding PELI items for each factor. Multiple regression models were used to relate predictors, including neuropsychiatric symptoms, to agreement levels. Results Four factors were identified from the PELI: autonomous choice, social engagement, personal growth, and keeping a routine. Significant participant-care partner discrepancy was found in “social engagement” preferences (e.g., regular contact with family, meeting new people, volunteering). Geriatric Depression Scale-15 score and care partner sex were significantly associated with participant-care partner discrepancies in “social engagement” preferences. Conclusion This study yields new insights regarding the most important preferences for persons with cognitive impairment and clarifies a path to optimizing surrogate decision-making around everyday preferences by highlighting areas of apparent disagreement and identifying potential predictors of discrepancy.

BACKGROUND: A protective association of dietary carotenoids with cognitive function has been suggested, but most studies have been relatively small with limited periods of follow-up. OBJECTIVES: We examined prospectively long-term intakes of carotenoids in relation to subjective cognitive function (SCF), a self-reported, validated indicator of cognitive dysfunction. METHODS: Among 49,493 female registered nurses with a mean age of 48 y in 1984, we used multinomial logistic regression to estimate the ORs and 95% CIs relating intakes of carotenoids to self-reported SCF in 2012 and 2014. Mean intakes of carotenoids were calculated from 7 repeated FFQs collected in 1984, 1986, and every 4 y afterwards until 2006. Self-reported SCF was assessed by a 7-item questionnaire on changes in memory and cognition; validity was supported by strong associations with Apolipoprotein E (APOE) ε4 genotype and concurrent cognitive function and cognitive decline measured by telephone-based neuropsychological tests. The mean values of scores assessed in 2012 and 2014 were categorized as “good” (0 points, 40.8%), “moderate” (0.5–2.5 points, 46.9%), and “poor” (3–7 points, 12.3%). RESULTS: Higher intake of total carotenoids was associated with substantially lower odds of moderate or poor cognitive function after controlling for other dietary and nondietary risk factors and total energy intake. Comparing the top with the bottom quintile of total carotenoids, the multivariable ORs were 0.86 (95% CI: 0.80, 0.93; P-trend

LEARNING OBJECTIVES After participating in this activity, learners should be better able to:• Identify risk factors for late-life depression• Evaluate strategies to prevent late-life depression ABSTRACT: Late-life depression (LLD) is one of the major sources of morbidity and mortality in the world. Because LLD is related to increased public health burden, excess health care costs and utilization, reduced quality of life, and increased mortality, prevention is a priority. Older adults differ from younger adults with respect to key features, such as their chronicity and lifetime burden of depression and their constellation of comorbidities and risk factors. LLD likely arises from a complex interplay of risk factors, including medical, physiologic, psychosocial, behavioral, and environmental factors. Thus, a comprehensive understanding of LLD risk factors is necessary to inform prevention strategies. In this narrative literature review, we address both the risk architecture of LLD and several potential strategies for prevention. Our description of LLD risk factors and prevention approaches is informed by the framework developed by the National Academy of Medicine (formerly, Institute of Medicine), which includes indicated, selective, and universal approaches to prevention.

Background Evidence regarding the role of diet quality, especially its change, in subjective cognitive decline (SCD) is scarce. Objectives To examine associations of long-term diet qualities, including Alternate Mediterranean Diet (AMED), Dietary Approaches to Stop Hypertension (DASH), and Alternate Healthy Eating Index 2010 (AHEI-2010) with SCD in the Nurses' Health Study. Methods We followed 49,493 female registered nurses averaged 48 years from 1984 to 2014. Diet scores were derived from seven repeated food frequency questionnaires in 1984, 1986, and every four years afterward until 2006. Self-reported SCD was assessed in 2012 and 2014 by a 7-item questionnaire on memory and cognition changes. Categorical SCD score was classified as "none" (0 points, 40.8%), "moderate" (0.5-2.5 points, 46.9%), and "severe" (3-7 points, 12.3%). Results Multinomial and linear regression models were adjusted for total calorie, demographic characteristics, major lifestyle, and clinical factors. Comparing top vs. bottom quintiles of AMED, DASH, and AHEI-2010, multivariable-adjusted odds ratios (ORs) (95% confidence intervals, CIs) for severe vs. none SCD were 0.57 (0.51, 0.64), 0.61 (0.55, 0.68), and 0.81 (0.73, 0.90), respectively. Similar associations remained for three diet indices evaluated 28 years before SCD assessment. Compared to participants with lowest diet quality tertiles in both remote and recent years, the lowest odds of severe SCD was observed among those who maintained highest diet quality tertiles over time, with a 40%, 32%, and 20% lower odds of severe SCD for AMED, DASH, and AHEI-2010, respectively. Moreover, the odds of severe SCD was lower among those with improved diets over time; for each standard deviation higher in diet quality change, reduced risks were 11% for AMED, 5% for DASH, and 3% for AHEI-2010, respectively. Conclusion Our findings support beneficial roles of long-term adherence to, and improvement in healthy dietary patterns for maintenance of subjective cognition in women.

Objectives To determine associations between geographic region and late-life depression (LLD) severity, item-level symptom burden, and treatment; to evaluate whether racial/ethnic disparities in LLD, previously observed in the overall sample, vary by region. Methods We included 25,502 VITAL (Vitamin D and Omega-3 Trial) participants and administered the Patient Health Questionnaire-8 for depressive symptoms; participants also reported medication and/or counseling care for depression. Multivariable regression analyses were performed. Results Despite overall lower LLD severity and item-level symptom burden in the Midwest vs. Northeast, higher LLD severity and item-level burden were observed among minorities, especially Black and Hispanic adults, compared to non-Hispanic whites in this region. Racial/ethnic disparities in item-level symptoms (e.g., anhedonia, sadness, psychomotor changes) varied by region. There were no significant differences in depression care by region; furthermore, regional variation was not observed in racial disparities in care: e.g., among those with clinician/physician-diagnosed depression, Blacks vs. non-Hispanic whites had >50% lower odds of treatment in all regions. Conclusion LLD varied by geographic region. Furthermore, magnitudes of racial/ethnic disparities in LLD severity and item-level symptom burden, but not depression care, differed by region.

Objectives Neuropsychiatric symptoms (NPS) of dementia are common and may be driven by inability of persons with cognitive impairment (CI) to communicate needs. We addressed the relevance of this unmet-needs model to burden of NPS among persons with milder CI. Methods The sample included 48 dyads of persons with CI and their care partners. NPS were measured at baseline and follow-up (mean 486 days +/-107 SD). Mixed random and fixed effects longitudinal models were used to evaluate impact of discrepancies between persons with CI and their care partners in everyday preferences (baseline) on changes in NPS over time. Results Higher levels of underestimation of "social engagement" preferences of persons with CI by care partners were associated with a higher average burden of NPS across all follow-up. Conclusions This study suggests that unmet-needs may be a useful construct for understanding etiology for NPS across the spectrum of severity of cognitive impairment.

Preventive strategies for frailty are needed. Whether supplements with anti-inflammatory properties, such as vitamin D3 or marine omega-3 fatty acids, are useful for frailty prevention is unknown.To test the effects of vitamin D3 and omega-3 supplements on change in frailty in older individuals.This study was conducted in 2021, as a prespecified ancillary to the Vitamin D and Omega-3 (VITAL) trial, a 2 × 2 factorial randomized clinical trial. A total of 25 871 individuals (men aged ≥50 years and women aged ≥55 years), without cancer or cardiovascular disease and with data on frailty, were recruited across all 50 US states from November 2011 to March 2014 and followed up through December 31, 2017. Data analysis for the ancillary study was conducted from December 1, 2019, to March 30, 2022.Vitamin D3, 2000 IU/d, and marine omega-3 fatty acids, 1 g/d.Frailty was measured using a validated 36-item frailty index that includes measures of function, cognition, mood, and comorbidities from annual questionnaires. Change in frailty score from baseline to year 5, according to randomization, using an intention-to-treat protocol, was assessed using repeated measures. Cox proportional hazards regression models assessed incident frailty. In subgroup analysis, an alternative frailty definition, the physical phenotype, was used as a sensitivity analysis.Of 25 871 VITAL trial participants randomized, 25 057 had sufficient data to calculate a frailty index. Baseline mean (SD) age was 67.2 (7.0) years, and 12 698 (50.7.%) were women. Mean (SD) frailty score was 0.109 (0.090) (range, 0.00-0.685), and 3174 individuals (12.7%) were frail. During a median 5-year follow-up, mean (SD) frailty scores increased to 0.121 (0.099) (range, 0.00-0.792). Neither vitamin D3 nor omega-3 fatty acid supplementation affected mean frailty scores over time (mean difference at year 5: vitamin D3, -0.0002; P = .85; omega-3 fatty acid, -0.0001; P = .90) or rate of change in mean frailty score (interaction with time: vitamin D3; P = .98; omega-3 fatty acid; P = .13) Incident frailty remained similar over time (interaction with time: vitamin D3, P = .90; omega-3 fatty acid; P = .32). Results were unchanged using the frailty physical phenotype.In this ancillary study of the VITAL randomized clinical trial, treatment with vitamin D3 or omega-3 fatty acid supplementation, compared with placebo, did not affect the rate of frailty change or incidence over time. These results do not support routine use of either vitamin D3 or omega-3 fatty acid supplementation for frailty prevention in generally healthy community-dwelling older adults not selected for vitamin D3 deficiency.ClinicalTrials.gov Identifier: NCT01169259.

Low vitamin D levels have been associated with cognitive decline; however, few randomized trials have been conducted. In a trial, we evaluated vitamin D3 supplementation on cognitive decline. We included participants aged 60+ years (mean[SD] = 70.9[5.8] years) free of cardiovascular disease and cancer in two substudies in the VITAL 2 × 2 randomized trial of vitamin D3 (2000 IU/day of cholecalciferol) and fish oil supplements: 3424 had cognitive assessments by phone (eight neuropsychologic tests; 2.8 years follow-up) and 794 had in-person assessments (nine tests; 2.0 years follow-up). The primary, pre-specified outcome was decline over two assessments in global composite score (average z-scores of all tests); substudy-specific results were meta-analyzed. The pooled mean difference in annual rate of decline (MD) for vitamin D3 versus placebo was 0.01 (95% CI − 0.01, 0.02; p = 0.39). We observed no interaction with baseline 25-hydroxyvitamin-D levels (p-interaction = 0.84) and a significant interaction with self-reported race (p-interaction = 0.01). Among Black participants (19%), those assigned vitamin D3 versus placebo had better cognitive maintenance (MD = 0.04, 95% CI 0.01, 0.08, similar to that observed for Black participants 1.2 years apart in age). Thus, vitamin D3 (2000 IU/day cholecalciferol) supplementation was not associated with cognitive decline over 2–3 years among community-dwelling older participants but may provide modest cognitive benefits in older Black adults, although these results need confirmation.Trial registration ClinicalTrials.gov; VITAL (NCT01169259), VITAL-DEP (NCT01696435) and VITAL-Cog (NCT01669915); the date the registration for the parent trial (NCT01169259) was submitted to the registry: 7/26/2010 and the date of first patient enrollment in either of the ancillary studies for cognitive function in a subset of eligible VITAL participants: 9/14/2011.

Background Recent studies suggest an intergenerational influence of stress such that maternal exposure even before pregnancy could impact offspring health outcomes later in life. In humans, investigations on the impact of maternal stressors on offspring health outcomes, including stress-sensitive biomarkers, have largely been limited to extreme stressors. Prior studies have not addressed more moderate maternal stressors, such as rotating night shift work, on offspring stress markers in young adulthood. Methods We investigated the association between maternal rotating night shift work before conception and offspring salivary cortisol and alpha amylase (sAA) patterns in young adulthood among mothers enrolled in the Nurses' Health Study II (NHSII) and their offspring participating in the Growing Up Today Study 2 (GUTS2). Our sample included over 300 mother-child pairs where, between 2011 and 2014, the children provided 5 saliva samples over the course of one day. We used piecewise linear mixed models to compare awakening responses, overall slopes as well as several other diurnal patterns of cortisol and sAA between offspring born to shift working versus non-shift working mothers. Results Offspring born to shift working mothers had a flattened late decline in cortisol (percent differences in slope (%D): 2.1%; 95%CI: 0.3, 3.8) and their sAA awakening response was steeper (%D -37.4%; 95%CI: −59.0, −4.4), whereas sAA increase before bedtime appeared less pronounced (%D -35.9%; 95%CI: −55.3, −8.3), compared to offspring born to mothers without shift work. For cortisol, we observed a significant difference in the Area Under the Curve (AUC) (%D 1.5%; 95%CI: 0.3, 2.7) with higher AUC for offspring of mothers who worked rotating night shifts. In offspring-sex-stratified analyses we found differences primarily among males. Conclusion Our results provide some – albeit modest - evidence that maternal rotating night shift work—a moderate stressor—influences offspring stress markers. Future studies with larger samples sizes, more detailed exposure assessment (particularly during maternal pregnancy), and multiple offspring biomarker assessments at different developmental stages are needed to further investigate these associations.

We investigated the relationship between maternal history of nightshift work before and shift work during pregnancy and offspring risk of depression and anxiety, among mothers participating in the Nurses Health Study II and in their offspring enrolled in the Growing Up Today Study 2 between 2004 and 2013. Case definitions were based on offspring self-reports of physician/clinician-diagnosed depression and/or anxiety, regular antidepressant use and depressive symptoms assessed using the Center for Epidemiologic Studies Depression Scale. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using generalized estimating equation models. We found no associations between maternal nightshift work before pregnancy or during pregnancy and offspring mental health disorders (e.g., nightshift work before pregnancy: depression (based on physician/clinician diagnosis): ORever nightwork = 1.14; 95% CI, 0.88–1.47; either depression or anxiety: ORever nightwork = 0.93; 95% CI, 0.81–1.08; nightshift work during pregnancy: depression: ORever nightwork = 1.14; 95% CI, 0.68–1.94; depression or anxiety: ORever nightwork =1.17; 95% CI, 0.70–1.98) and no dose-response relationship with longer history of nightshift work (all PTrend >0.10). Stratifying by maternal chronotype revealed a higher risk of depression for offspring whose mothers worked nightshifts before pregnancy and reported being definite morning chronotypes (a proxy for circadian strain) (ORever nightwork = 1.95; 95% CI, 1.17, 3.24 vs. ORever nightwork = 0.93; 95% CI, 0.68, 1.28 for any other chronotype; PInteraction = 0.03). Further studies replicating our findings and refined understanding regarding the interplay of nightshift work and chronotype and its potential influences on offspring mental health are needed. Electronic supplementary material The online version of this article (10.1007/s10654-019-00525-2) contains supplementary material, which is available to authorized users.

Background Telomeres cap and protect DNA but shorten with each somatic cell division. Aging and environmental and lifestyle factors contribute to the speed of telomere attrition. Current evidence suggests a link between relative telomere length (RTL) and depression but the directionality of the relationship remains unclear. We prospectively examined associations between RTL and subsequent depressive symptom trajectories. Methods Among 8,801 women of the Nurses' Health Study, depressive symptoms were measured every 4 years from 1992 to 2012; group-based trajectories of symptoms were identified using latent class growth-curve analysis. Multinomial logistic models were used to relate midlife RTLs to the probabilities of assignment to subsequent depressive symptom trajectory groups. Results We identified four depressive symptom trajectory groups: minimal depressive symptoms (62%), worsening depressive symptoms (14%), improving depressive symptoms (19%), and persistent-severe depressive symptoms (5%). Longer midlife RTLs were related to significantly lower odds of being in the worsening symptoms trajectory versus minimal trajectory but not to other trajectories. In comparison with being in the minimal symptoms group, the multivariable-adjusted odds ratio of being in the worsening depressive symptoms group was 0.78 (95% confidence interval, 0.62-0.97; p = 0.02), for every standard deviation increase in baseline RTL. Conclusions In this large prospective study of generally healthy women, longer telomeres at midlife were associated with significantly lower risk of a subsequent trajectory of worsening mood symptoms over 20 years. The results raise the possibility of telomere shortening as a novel contributing factor to late-life depression.

IMPORTANCE: Low levels of 25-hydroxyvitamin D have been associated with higher risk for depression later in life, but there have been few long-term, high-dose large-scale trials. OBJECTIVE: To test the effects of vitamin D(3) supplementation on late-life depression risk and mood scores. DESIGN, SETTING, AND PARTICIPANTS: There were 18 353 men and women aged 50 years or older in the VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention) ancillary study to VITAL, a randomized clinical trial of cardiovascular disease and cancer prevention among 25 871 adults in the US. There were 16 657 at risk for incident depression (ie, no depression history) and 1696 at risk for recurrent depression (ie, depression history but no treatment for depression within the past 2 years). Randomization occurred from November 2011 through March 2014; randomized treatment ended on December 31, 2017, and this was the final date of follow-up. INTERVENTION: Randomized assignment in a 2 × 2 factorial design to vitamin D(3) (2000 IU/d of cholecalciferol) and fish oil or placebo; 9181 were randomized to vitamin D(3) and 9172 were randomized to matching placebo. MAIN OUTCOMES AND MEASURES: The primary outcomes were the risk of depression or clinically relevant depressive symptoms (total of incident and recurrent cases) and the mean difference in mood scores (8-item Patient Health Questionnaire depression scale [PHQ-8]; score range, 0 points [least symptoms] to 24 points [most symptoms]; the minimal clinically important difference for change in scores was 0.5 points). RESULTS: Among the 18 353 randomized participants (mean age, 67.5 [SD, 7.1] years; 49.2% women), the median treatment duration was 5.3 years and 90.5% completed the trial (93.5% among those alive at the end of the trial). Risk of depression or clinically relevant depressive symptoms was not significantly different between the vitamin D(3) group (609 depression or clinically relevant depressive symptom events; 12.9/1000 person-years) and the placebo group (625 depression or clinically relevant depressive symptom events; 13.3/1000 person-years) (hazard ratio, 0.97 [95% CI, 0.87 to 1.09]; P = .62); there were no significant differences between groups in depression incidence or recurrence. No significant differences were observed between treatment groups for change in mood scores over time; mean change in PHQ-8 score was not significantly different from zero (mean difference for change in mood scores, 0.01 points [95% CI, −0.04 to 0.05 points]). CONCLUSIONS AND RELEVANCE: Among adults aged 50 years or older without clinically relevant depressive symptoms at baseline, treatment with vitamin D(3) compared with placebo did not result in a statistically significant difference in the incidence and recurrence of depression or clinically relevant depressive symptoms or for change in mood scores over a median follow-up of 5.3 years. These findings do not support the use of vitamin D(3) in adults to prevent depression. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT01169259 and NCT01696435

Few studies have evaluated the association between a healthful plant-based diet and health-related quality of life (HRQoL). We followed 50 290 women in the Nurses’ Health Study (NHS; 1992–2000) and 51 784 women in NHSII (1993–2001) for 8 years to investigate changes in plant-based diet quality in relation to changes in physical and mental HRQoL. Plant-based diet quality was assessed by three plant-based diet indices: overall plant-based diet index (PDI), healthful PDI (hPDI) and unhealthful PDI (uPDI). Physical and mental HRQoL were measured by physical component score (PCS) and mental component score (MCS) of the 36-Item Short Form Health Survey. Diet was assessed 2 years before the HRQoL measurements and both were updated every 4 years. The associations between 4-year changes in PDIs and HRQoL were evaluated. Each 10-point increase in PDI was associated with an improvement of 0·07 (95 % CI 0·01, 0·13) in PCS and 0·11 (95 % CI 0·05, 0·16) in MCS. A 10-point increase in hPDI was associated with an increment of 0·13 (95 % CI 0·08, 0·19) in PCS and 0·09 (95 % CI 0·03, 0·15) in MCS. Conversely, a 10-point increase in uPDI was associated with decreases in PCS and MCS (−0·07 (95 % CI −0·12, −0·02) and −0·10 (95 % CI −0·16, −0·05), respectively). Compared with a stable diet, an increase in hPDI was significantly associated with improvements in physical HRQoL in older women and with mental HRQoL in younger women. In conclusion, adherence to a healthful plant-based diet was modestly associated with improvements in both physical and mental dimensions of HRQoL.

Background Adherence to healthy lifestyles/behaviours promotes healthy ageing. However, little is known about whether age, sex and/or race/ethnicity moderate associations of lifestyle/behavioural factors with relative telomere length (RTL), a potential biomarker of ageing. Methods We included 749 midlife to older non-Hispanic White (n = 254), Black (n = 248) and Hispanic (n = 247) US participants [mean (standard deviation) age = 69.3 (7.2) years; women: 50.5%]. We extracted genomic DNA from peripheral leucocytes. RTL was assayed using real-time quantitative polymerase chain reaction. Multivariable regression was used to examine associations between lifestyle/behavioural exposures (i.e. physical activity, alcohol consumption, smoking and depression) with RTL. Results Increasing chronological age was associated with shorter RTL (P Conclusion We observed novel variations by sex and race/ethnicity in associations between lifestyle/behavioural factors and RTL. Further work is needed to replicate these findings and to address potential public health implications for modifying strategies by sex or across racial/ethnic groups to optimise lifestyles/behaviours for healthy ageing.

Mitochondrial DNA copy number (mtDNAcn) is a putative biomarker of oxidative stress and biological aging. Modifiable factors, including physical activity (PA), avoidance of heavy alcohol use and smoking, and maintaining good mental health, may reduce oxidative stress and promote healthy aging. Yet, limited data exist regarding how these factors are associated with mtDNAcn or whether age, sex or race/ethnicity moderate associations. In this cross-sectional study, we selected 391 adults (183 non-Hispanic White, 110 Black and 98 Hispanic; mean = 67 years) from the VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention) ancillary to the VITAL trial. We estimated associations between lifestyle and behavioral factors (PA, alcohol consumption, cigarette smoking and depression) and log-transformed mtDNAcn using multivariable linear regression models. MtDNAcn was not correlated with chronological age; women had ~17% higher mtDNAcn compared to men. There were no significant associations between PA measures (frequency, amount or intensity) or alcohol consumption with mtDNAcn. Cigarette smoking (per 5 pack-years) was significantly associated with mtDNAcn (percent difference = -2.9% (95% confidence interval (CI) = -5.4%, -0.4%)); a large contrast was observed among heavy vs. non-smokers (≥30 vs. 0 pack-years): percent difference = -28.5% (95% CI = -44.2%, -8.3%). The estimate of mtDNAcn was suggestively different for past vs. no depression history (percent difference = -15.1% 95% CI = -30.8%, 4.1%), but this difference was not statistically significant. The association between smoking and log-mtDNAcn varied by sex and race/ethnicity; it was stronger in men and Black participants. While chance findings cannot be excluded, results from this study support associations of smoking, but not chronological age, with mtDNAcn and suggest nuanced considerations of mtDNAcn as indicative of varying oxidative stress states vs. biological aging itself.

ObjectiveTo evaluate the prospective association of long-term intake of vegetables and fruits with late-life subjective cognitive function (SCF).MethodsAmong 27,842 men with a mean age of 51 years in 1986, we used multinomial logistic regression to examine the relation of vegetable and fruit consumption to future SCF. Average dietary intake was calculated from 5 repeated food frequency questionnaires collected every 4 years until 2002. SCF score was assessed twice (2008 and 2012) using a 6-item questionnaire; validity was supported by strong associations with APO ε4 genotype. We categorized the average of the 2 scores as good, moderate, and poor SCF.ResultsHigher intakes of total vegetables, total fruits, and fruit juice were each significantly associated with lower odds of moderate or poor SCF after controlling for major nondietary factors and total energy intake. The association with total fruit intake was weaker after further adjusting for major dietary factors. In this model, the multivariate odds ratios (95% confidence intervals) for vegetable intake (top vs bottom quintile) were 0.83 (0.76–0.92), p trend p trend p trend ConclusionOur findings support a long-term beneficial role of vegetable, fruit, and orange juice consumption on SCF.

BACKGROUND: Prior cross-sectional studies have suggested that being a late chronotype is associated with depression and depressive symptoms, but prospective data are lacking. METHODS: We examined the association between chronotype and incident depression (defined as self-reported physician/clinician-diagnosed depression or antidepressant medication use) in 32,470 female participants of the Nurses’ Health Study II cohort who self-reported their chronotype (early, intermediate or late) and were free of depression at baseline in 2009 (average age: 55 yrs). Women updated their depression status on biennial questionnaires in 2011 and 2013. We used multivariable (MV)-adjusted Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for incident depression across chronotype categories (i.e., early, intermediate, and late chronotypes). RESULTS: Across a follow-up period of 4 years, we observed 2,581 cases of incident depression in this cohort. Compared to intermediate chronotypes, early chronotypes had a modestly lower risk of depression after MV adjustment (MVHR=0.88, 95%CI=0.81–0.96), whereas late chronotypes had a similar risk of 1.06 (95%CI=0.93–1.20); the overall trend across chronotype categories was statistically significant (ptrend

Rationale Depression is a leading cause of disease burden and disability for older adults; thus, prevention is a priority. Biologic and observational data support potential mental health benefits of vitamin D and omega-3 fatty acids; however, it is unclear whether these supplements can prevent late-life depression. Design We describe the novel methodology of a large-scale study: VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention), an ancillary to the VITAL trial. Primary Aims of VITAL-DEP are to determine effects on prevention of depression and on trajectory of mood symptoms of long-term (mean = 5 years) supplementation with vitamin D (vitamin D3 [cholecalciferol], 2000 IU/day) and marine omega-3 fatty-acids (eicosapentaenoic acid + docosahexaenoic acid, 1 g/day), in a 2 × 2 factorial design, among 25,874 older adults. Secondary Aims will evaluate: vitamin D's effects among African-Americans (an at-risk group for vitamin D deficiency); both agents' effects among those with high-risk factors or sub-syndromal depression in a sub-set of ~1000 participants with detailed examinations at baseline and 2-year follow-up; whether baseline nutrient levels influence depression risk and/or modify agents' effects. Additional planned analyses will use pre-randomization blood samples available in ~17,000 participants to address whether key biomarkers and factors influence long-term mood and depression risk and/or the agents' effects. Conclusion VITAL-DEP applies all modalities of state-of-the-art prevention research – universal, selective and indicated. VITAL-DEP will clarify effects of supplemental vitamin D and/or omega-3 on mood, and inform clinical care and public health guidelines on the use of these agents for prevention of depression in mid-life and older adults.

Background: Depression and antidepressant use is highly prevalent among U.S. women and may be related to increased breast cancer risk. However, prior studies are not in agreement regarding an increase in risk. Methods: We conducted a prospective cohort study within the Nurses' Health Study (NHS) and NHSII among females age 25 and older. Over more than 10 years of follow-up in each cohort, 4,014 incident invasive breast cancers were diagnosed. We used Cox proportional hazards regressions with updating of exposures and covariates throughout follow-up to estimate HRs and 95% confidence intervals (CIs) for associations between clinical depression and antidepressant use with invasive breast cancer risk. Analyses were repeated separately for in situ disease, as well as stratified by estrogen receptor (ER) subtype and menopausal status at diagnosis. Results: No statistically significant associations were observed between clinical depression (HR for reporting ≥3 times vs. 0, 1.13; 95% CI, 0.85–1.49) or antidepressant use (HR for reporting ≥3 times vs. 0, 0.92; 95% CI, 0.80–1.05) and invasive breast cancer risk in multivariable analyses. Likewise, we observed no significant associations between clinical depression or antidepressant use and risk of in situ, ER+, ER−, premenopausal, or postmenopausal breast cancer. Conclusions: In the largest prospective study to date, we find no evidence that either depression or antidepressant use increase risk of breast cancer. Impact: The results of this study are reassuring in that neither depression nor antidepressant use appear to be related to subsequent breast cancer risk. Cancer Epidemiol Biomarkers Prev; 27(3); 306–14. ©2017 AACR.

Background Research links psychological stress to accelerated cellular aging. Here we examined whether long-term patterns of depression and caregiving burden, forms of chronic psychological stress, were associated with shorter telomere length, a biomarker of cellular aging. Methods The study included 1250 healthy older women (mean: 68.0; range: 60–81 years) in the Nurses’ Health Study. Long-term patterns in depressive symptoms and caregiving activity (separated into care of children/grandchildren vs. ill or disabled family members/others) incorporated questionnaire data between 1992 and 2000; relative leukocyte telomere lengths (LTLs) were measured in 2000–2001. Least-squares means LTL z-scores were calculated across categories of depression patterns and caregiving intensity. Results Six empirically-derived latent classes of depressive symptom trajectories were identified: minimal-stable (63.7%), mild-worsening (3.9%), subthreshold-improving (22.8%), subthreshold-worsening (2.7%), clinical range depressive-improving (6.2%), and clinical range depressive-persistent (0.6%). After collapsing trajectory patterns into 4 groups (combining those with minimal and mild symptoms into one group and those with clinical range depressive symptoms into one group) due to very small sample sizes in some groups, we observed marginal associations (p = 0.07): e.g., the least-squares means LTL z-scores were lowest (−0.08; 95% CI: −0.22 to 0.06) for the clinical range depressive symptoms group and highest (0.12; 0.04–0.20) for the subthreshold-improving group (Tukey’s post-hoc pairwise p = 0.07). With six depressive symptom trajectories, no significant associations were observed with regard to telomere lengths. There were no significant associations between caregiving intensity and LTLs. Conclusions There were no associations between long-term patterns of caregiving burden and telomere lengths among older women. Possible differences in telomere lengths by types of long-term depressive symptom trajectories may warrant further investigation.

Background Although depression and anxiety have been associated with shorter telomeres in cross-sectional studies, the data regarding the prospective relations of depression and anxiety to accelerated telomere length shortening are limited and findings are mixed. We prospectively examined relations of baseline depression and phobic anxiety to subsequent 11-year change in relative leukocyte telomere lengths (LTLs). Methods We selected 1,250 women from a subcohort of the Nurses' Health Study who provided blood specimens at both blood collections (1989-1990 and 2000-2001). Depression was defined by self-reported regular antidepressant use or presence of severe depressive symptoms; anxiety symptoms were assessed using the Crown-Crisp Experiential Index. Using quantitative real-time polymerase chain reaction assay, LTLs were measured as the copy number ratio of telomere repeat to a single control gene. Changes in LTLs were defined in three ways: absolute change, symmetrized percent change, and decile shift. Results Overall, there were no statistically significant associations of depression or phobic anxiety to subsequent 11-year LTL shortening, despite a point estimates in the direction of greater telomere shortening among participants with versus without depression, across all three metrics of telomere change. The strongest predictor of LTL change was baseline telomere length, and regression-to-the-mean was observed. Conclusion Baseline depression and phobic anxiety were not significantly associated with 11-year attrition in LTLs among 1,250 mid-life and older women. However, a suggestion of depression and greater subsequent LTL attrition, while not statistically significant, may warrant further inquiry, particularly in prospective studies with larger sample sizes and broader windows of the lifespan.

IMPORTANCE: Marine omega-3 fatty acid (omega-3) supplements have been used to treat depression but their ability to prevent depression in the general adult population is unknown. OBJECTIVE: To test effects of omega-3 supplementation on late-life depression risk and mood scores. DESIGN, SETTING, AND PARTICIPANTS: A total of 18 353 adults participated in the VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention) ancillary study to VITAL, a randomized trial of cardiovascular disease and cancer prevention among 25 871 US adults. There were 16 657 at risk of incident depression (no previous depression) and 1696 at risk of recurrent depression (previous depression, but not for the past 2 years). Randomization occurred from November 2011 through March 2014; randomized treatment ended on December 31, 2017. INTERVENTIONS: Randomized 2 × 2 factorial assignment to vitamin D(3) (2000 IU/d), marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid and 375 mg of docosahexaenoic acid) or placebo; 9171 were randomized to omega-3 and 9182 were randomized to matching placebo. MAIN OUTCOMES AND MEASURES: Prespecified coprimary outcomes were risk of depression or clinically relevant depressive symptoms (total of incident + recurrent cases); mean difference in mood score (8-item Patient Health Questionnaire [PHQ-8] depression scale). RESULTS: Among 18 353 participants who were randomized (mean age, 67.5 [SD, 7.1] years; 49.2% women), 90.3% completed the trial (93.5% among those alive at the end of the trial); the median treatment duration was 5.3 years. The test for interaction between the omega-3 and the vitamin D agents was not significant (P for interaction = .14). Depression risk was significantly higher comparing omega-3 (651 events, 13.9 per 1000 person-years) with placebo (583 events, 12.3 per 1000 person-years; hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P = .03). No significant differences were observed comparing omega-3 with placebo groups in longitudinal mood scores: the mean difference in change in PHQ-8 score was 0.03 points (95% CI, −0.01 to 0.07; P = .19). Regarding serious and common adverse events, the respective prevalence values in omega-3 vs placebo groups were major cardiovascular events (2.7% vs 2.9%), all-cause mortality (3.3% vs 3.1%), suicide (0.02% vs 0.01%), gastrointestinal bleeding (2.6% vs 2.7%), easy bruising (24.8% vs 25.1%), and stomach upset or pain (35.2% vs 35.1%). CONCLUSIONS AND RELEVANCE: Among adults aged 50 years or older without clinically relevant depressive symptoms at baseline, treatment with omega-3 supplements compared with placebo yielded mixed results, with a small but statistically significant increase in risk of depression or clinically relevant depressive symptoms but no difference in mood scores, over a median follow-up of 5.3 years. These findings do not support the use of omega-3 supplements in adults to prevent depression. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT01696435 and NCT01169259

Despite recently reported associations between air pollution and acute psychiatric outcomes, the association with depression onset has not, to our knowledge, been previously examined. We conducted a prospective cohort study among 41,844 women in the Nurses' Health Study, in the United States. The women had an average age of 66.6 (standard deviation, 7.6) years, were depression-free in 1996, and were followed through 2008. May-September ozone exposures were predicted by interpolating concentrations from the 5 nearest monitors. One-, 2-, and 5-year average concentrations of particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM2.5) were predicted at each participant's residence using a spatiotemporal model. We defined depression as report of doctor's diagnosis or use of antidepressant medication. We estimated adjusted hazard ratios with time-varying Cox models. Hazard ratios for both pollutants were elevated (per 10-parts-per-billion increase in ozone, hazard ratio (HR) = 1.06; 95% confidence interval (CI): 1.00, 1.12; per 10-μg/m3 increase in 1-year PM2.5, HR = 1.08; 95% CI: 0.97, 1.20). Associations were stronger when only antidepressant use was used to define cases (for ozone, HR = 1.08; 95% CI: 1.02, 1.14; for PM2.5, HR = 1.12; 95% CI: 1.00, 1.25). To our knowledge, these results represent the first identification of a possible association between both long-term ozone and PM2.5 exposure and depression onset. Although the stronger association specifically with antidepressant use may reflect that this endpoint better captures the onset time and milder cases, our findings should be interpreted with caution.

Background Low maternal vitamin D levels [serum 25-hydroxyvitamin D (25(OH)D)] during pregnancy have been linked to offspring neuropsychiatric outcomes such as schizophrenia and autism, but studies on depression are lacking. We examined the association between maternal vitamin D status during pregnancy and offspring depression during childhood and adolescence and investigated whether any associations were modified by offspring genetic risk for depression. Methods Mother-singleton birth offspring pairs in the Avon Longitudinal Study of Parents and Children (ALSPAC) that had maternal 25(OH)D measurements, offspring genetic data, and offspring depression measures collected in childhood (mean age=10.6 years; n = 2938) and/or adolescence (mean age=13.8 years; n = 2485) were included in the analyses. Using multivariable logistic regression, we assessed associations between maternal vitamin D status and offspring polygenic risk score (PRS) for depression on childhood/adolescent depression risk. Results There was no evidence for an association between maternal vitamin D status during pregnancy and offspring depression in childhood (p = 0.72) or adolescence (p = 0.07). Offspring depression PRS were independently associated with childhood depression (p = 0.003), but did not interact with maternal vitamin D status. These results were robust to adjustments for potential confounders and different cut-offs for vitamin D insufficiency/deficiency. Limitations 25(OH)D measurements were only available at a single time point during pregnancy. Conclusion These findings suggest that maternal vitamin D status during pregnancy does not affect an offspring's risk for early life depression.

Relations of DNA methylation markers to other biological aging markers and to psychosocial, behavioral, and health measures remain unclear. The sample included 23 participants (n = 11 cases with psychiatric diagnoses and n = 12 controls without current or lifetime psychiatric disorder), balanced by age and sex. Genomic DNA was extracted from blood samples; the following were performed: genome-wide DNA methylation assay using Illumina 850k methylationEPIC; PCR assays for relative telomere length (RTL) and mitochondrial DNA copy number (mtCN). Exposures were: case status; depression and anxiety symptoms; psychosocial support; subjective and objective cognition. Outcomes were: DNA methylation age (DNAm age); RTL; mtCN; extrinsic and intrinsic epigenetic age acceleration (EEAA and IEAA). Stronger correlation with chronological age was observed for DNAm age (ρ = 0.86; p ρ = −0.53; p ρ = 0.36; p = 0.10); smoking pack-years (ρ = 0.37; p = 0.08); physical activity (ρ = −0.56; p = 0.01); alcohol intake (ρ = 0.56; p = 0.01). DNAm age was inversely correlated with psychosocial support (ρ = −0.42; p = 0.048) and Modified Mini-Mental State score (ρ = −0.44; p = 0.01). Anxiety, psychosocial support, and objective cognition were significantly related to accelerated aging; depression and subjective cognition were not. In conclusion, DNAm age correlated more strongly with chronological age and key psychosocial, behavioral, and health variables than RTL or mtCN. Signals for associations with epigenetic aging were observed for psychosocial and neurobehavioral variables.

Background: Recent evidence suggests that higher levels of residential greenness may contribute to better mental health. Despite this, few studies have considered its impact on depression, and most are cross-sectional. Objective: The objective of this study was to examine surrounding residential greenness and depression risk prospectively in the Nurses’ Health Study. Methods: A total of 38,947 women (mean age throughout follow-up 70 y [range 54–91 y]) without depression in 2000 were followed to 2010. Residential greenness was measured using the satellite-based Normalized Difference Vegetation Index (NDVI) and defined as the mean greenness value within 250-m and 1,250-m radii of the women’s residences in July of each year. Incidence of depression was defined according to the first self-report of either physician-diagnosed depression or regular antidepressant use. We used Cox proportional hazards models to examine the relationship between greenness and depression incidence and assessed physical activity as a potential effect modifier and mediator. Results: Over 315,548 person-years, 3,612 incident depression cases occurred. In multivariable-adjusted models, living in the highest quintile of residential greenness within 250m was associated with a 13% reduction in depression risk (HR=0.87 [95% confidence interval (CI): 0.78, 0.98]) compared with the lowest quintile. The association between greenness and depression did not appear to be mediated by physical activity, nor was there evidence of effect modification by physical activity. Conclusions: In this population of mostly white women, we estimated an inverse association between the highest level of surrounding summer greenness and the risk of self-reported depression. https://doi.org/10.1289/EHP1229

Objective Low social integration and divorce/widowhood are chronic psychosocial stressors that may affect health. When assessed after cancer diagnosis, they have been associated with poorer survival, but their role in cancer development, particularly ovarian cancer (OvCA), is less understood. We investigated whether social integration and marital status were related to OvCA risk in a large population-based study. Methods Women from the Nurses' Health Study completed the Berkman-Syme Social Network Index and reported their marital status every 4 years starting in 1992 (N = 72,206), and were followed up until 2012 (20-year follow-up period). Multivariate Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of OvCA risk, considering relevant potential confounders, in lagged analyses whereby psychosocial indicators were assessed 4 to 8 years (n = 436 cases) and 8 to 12 years (n = 306 cases) before diagnosis to account for the effects of prediagnostic symptoms on social measures. Secondary analyses evaluated the stability of and cumulative exposure to these social factors on OvCA risk. Results Being socially isolated versus integrated was related to an increased OvCA risk 8 to 12 years later (HR = 1.51, 95% CI = 1.07-2.13), but not 4 to 8 years later. Compared with married women, OvCA risk was significantly higher in widowed but not in separated/divorced individuals, with both time periods (e.g., 8-12 years later: HRwidowed = 1.57 [95% CI = 1.15-2.14] versus HRseparated/divorced = 1.13 [95% CI = 0.74-1.72]). Estimates were comparable or stronger when investigating stability in and cumulative effects of social indicators. Conclusions Results suggest higher OvCA risk among socially isolated and widowed women, particularly when such psychosocial stressors were experienced a decade before diagnosis or were sustained over time.

Objective To assess racial variation in depression risk factors and symptom trajectories among older women. Methods Using Nurses' Health Study data, participants (29,483 non-Hispanic white and 288 black women) aged 60 years or older, free of depression in 2000, were followed until 2012. Data on race and risk factors, selected a priori, were obtained from biennial questionnaires. Incident depression was defined as depression diagnosis, antidepressant use, or presence of severe depressive symptoms. Group-based trajectories of depressive symptoms were determined using latent variable modeling approaches. Results Black participants had lower risk (hazard ratio: 0.76; 95% confidence interval: 0.57–0.99) of incident late-life depression compared with whites. Although blacks had higher prevalence than whites of some risk factors at study baseline, distributions of major contributors to late-life depression risk (low exercise, sleep difficulty, physical/functional limitation, pain) were comparable. There was evidence of effect modification by race for relations of region of birth (Southern birthplace), smoking, and medical comorbidity to depression risk; however, wide confidence intervals occurred among blacks because of smaller sample size. Four trajectories were identified: minimal symptoms-stable (58.3%), mild symptoms-worsening (31.4%), subthreshold symptoms-worsening (4.8%), and subthreshold symptoms-improving (5.5%). Probabilities of trajectory types were similar for blacks and whites. Conclusion Although overall trajectories of late-life depressive symptoms were comparable by race, there was racial variation in depression risk estimates associated with less-studied factors, such as U.S. region of birth. Future work may address unmeasured health and resilience determinants that may underlie observed findings and that could inform clinical assessment of late-life depression risk factors.

Objectives. To review the contribution of the Nurses’ Health Studies (NHS) on factors that influence mental and physical health. Methods. Narrative review of all published articles using data from the NHS, the NHS II, and the Growing Up Today Study focusing on mental health conditions (e.g., depression, posttraumatic stress disorder, anxiety) and psychosocial resources and stressors (e.g., job strain, interpersonal violence, social relationships, sexual orientation) between 1990 and 2016. Results. Studies have considered a broad array of determinants (e.g., genes, biomarkers, air pollution) and consequent behavioral and disease-related outcomes (e.g., body weight, smoking, cardiometabolic diseases, cancer, autism). Findings suggest anxiety, posttraumatic stress disorder, childhood violence, caregiver burden, and job insecurity may increase the risk of coronary heart disease and diabetes, whereas findings with cancer are mixed. This work directly affects public health actions, as demonstrated by recent inclusion of a gender expression measure in state surveys. Conclusions. The NHS cohorts have produced novel and influential research on the interplay of psychological and social factors with health. Psychological and social variables are important contributors to the maintenance or decline of physical and mental health.

Debate continues on how to measure and weight diseases in multimorbidity. We quantified the association of a broad range of chronic diseases with physical health-related qualify of life and used these weights to develop and validate a multimorbidity weighted index (MWI). Community-dwelling adults in 3 national, prospective studies-the Nurses' Health Study (n = 121,701), Nurses' Health Study II (n = 116,686), and Health Professionals Follow-up Study (n = 51,529)-reported physician-diagnosed diseases and completed the Short Form 36 physical functioning (PF) scale over multiple survey cycles between 1992 and 2008. Mixed models were used to obtain regression coefficients for the impact of 98 morbid conditions on PF. The MWI was formed by weighting conditions by these coefficients and was validated through bootstrapping. The final sample included 612,592 observations from 216,890 participants (PF mean score = 46.5 (standard deviation, 11)). The association between diseases and PF varied severalfold (median, -1.4; range, -10.6 to 0.8). End-stage organ diseases were associated with the greatest reduction in PF. The mean MWI score was 4.8 (median, 3.7; range, 0-53), and the mean number of comorbid conditions was 3.3 (median, 2.8; range, 0-34). This validated MWI weights diseases by severity using PF, a patient-centered outcome. These results suggest that simple disease count is unlikely to capture the full impact of multimorbidity on health-related quality of life, and that the MWI is feasible and readily implemented.

Background In this article, we review current evidence regarding potential benefits of vitamin D for improving mood and reducing depression risk in older adults. We summarize gaps in knowledge and describe future efforts that may clarify the role of vitamin D in late-life depression prevention. Methods MEDLINE and PsychINFO databases were searched for all articles on vitamin D and mood that had been published up to and including May 2015. Observational studies and randomized trials with 50 or more participants were included. We excluded studies that involved only younger adults and/or exclusively involved persons with current depression. Results Twenty observational (cross-sectional and prospective) studies and 10 randomized trials (nine were randomized placebo-controlled trials [RCTs]; one was a randomized blinded comparison trial) were reviewed. Inverse associations of vitamin D blood level or vitamin D intake with depression were found in 13 observational studies; three identified prospective relations. Results from all but one of the RCTs showed no statistically significant differences in depression outcomes between vitamin D and placebo groups. Limitations Observational studies were mostly cross-sectional and frequently lacked adequate control of confounding. RCTs often featured low treatment doses, suboptimal post-intervention changes in biochemical levels of vitamin D, and/or short trial durations. Conclusion Vitamin D level-mood associations were observed in most, but not all, observational studies; results indicated that vitamin D deficiency may be a risk factor for late-life depression. However, additional data from well-designed RCTs are required to determine the impact of vitamin D in late-life depression prevention.

Background Depression and the metabolic syndrome (MetS) are both risk factors for cardiovascular disease and type 2 diabetes mellitus. Prior studies in predominantly White populations demonstrated that individuals with depressive symptoms at baseline are more likely to develop future MetS. We tested the hypothesis that depressive symptoms would contribute to a more pronounced increase in MetS severity among African Americans in the Jackson Heart Study (JHS). Methods We used repeated-measures modeling among 1743 JHS participants during Visits 1–3 over 8 years of follow-up to evaluate relations between depressive symptom score (Center for Epidemiologic Survey-Depression (CES-D)) at baseline and a sex- and race/ethnicity-specific MetS severity Z-score at each visit. Results 20.3% of participants had a CES-D score ≥16, consistent with clinically-relevant depressive symptoms. Higher depressive-symptom scores were associated with higher MetS severity in women but not men (p = 0.005 vs. p = 0.490). There was no difference by depressive symptom score with rate of change in MetS severity over time. Both depressive-symptom score and MetS severity Z-score were associated with lower levels of physical activity and higher levels of C-reactive protein; however, addition of these to the regression model did not attenuate the association between depressive symptoms and MetS severity. Conclusion African American women but not men in the JHS exhibit relationships between baseline depressive symptoms and MetS severity over an 8-year period. These data may have implications for targeting of MetS-associated lifestyle changes among individuals with depressive symptoms.

Purpose: To identify attributes related to glaucoma diagnosis or early glaucoma treatment patterns that are associated with changes in health-related quality of life among those with newly diagnosed primary open-angle glaucoma. Methods: Among Nurses' Health Study participants with incident medical record-confirmed primary open-angle glaucoma diagnosed in 1992 to 2000, we included 317 women who completed the Short Form-36 Health Survey prediagnosis and postdiagnosis. The 2 primary outcomes were 4-year changes (1992 to 1996 or 1996 to 2000) in the physical and mental component summary scores. Multiple regression models were used to estimate differences in score changes by early treatment pattern history and characteristics as of diagnosis (ie, number of eyes affected, history of cataract, macular degeneration, cup-to-disc ratio, intraocular pressure, visual field loss type). Results: In multivariable models, no ophthalmologic characteristics were associated with physical component score change. However, compared with treatment with eye drops or pills only, laser trabeculoplasty treatment (concomitant with history of treatment with eye drops or pills in 84%) was associated with a worse mental component score change over 4 years (-2.5 units; 95% confidence interval: -4.6, -0.3); this association was stronger with a family history of glaucoma (P-interaction=0.04) or with bilateral disease (P-interaction=0.001). Conclusions: Among patients with incident glaucoma, no major factors were associated with change in physical well being. However, compared with medical treatment only, a history of laser trabeculoplasty, which was commonly accompanied with a history of medical treatment and likely represented the need for a second line of treatment, was associated with a worse decline in mental well being.

We aimed to test the hypothesis that serum 25-hydroxyvitamin D3 (25(OH)D) concentration is associated with mental health and life stress measures in young adults and investigate gender and racial disparities in these associations. This study comprised 327 black and white participants. Depression, trait anxiety, perceived stress, and hostility were measured by the following validated instruments: Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS), and Cook&ndash, Medley Hostility Scale (CMHS). Linear regression was used to estimate correlations between serum 25(OH)D concentration and mental health measurements in the total population and in subgroups stratified by gender and race. In this sample (28.2 &plusmn, 3.1 years, 52% female, 53% black), serum 25(OH)D concentration was negatively related to BDI, STAI, PSS, total CMHS score, and the majority of CMHS subscale scores (p-values &lt, 0.05). Stratified by gender, most of these associations remained significant only in women (p-values &lt, 0.05). Stratified by race, higher 25(OH)D concentrations in white participants were significantly related to lower BDI, STAI, PSS, and CMHS-cynicism subscales (p-values &lt, 0.05), 25(OH)D concentrations in the black participants were only inversely associated with CMHS and most CMHS subscales (p-values &lt, 0.05) but not with BDI, STAI, and PSS. We present novel findings of consistent inverse relationships between serum 25(OH)D concentration and various measures of mental health and life stress. Long-term interventional studies are warranted in order to investigate the roles of vitamin D supplementation in the prevention and mitigation of depression, anxiety, and psychological stress in young adults.

IntroductionCurrent evidence indicates that older racial/ethnic minorities encounter disparities in depression care. Because late-life depression is common and confers major adverse health consequences, it is imperative to reduce disparities in depression care. Thus, the primary objectives of this protocol are to: (1) quantify racial/ethnic disparities in depression treatment and (2) identify and quantify the magnitude of these disparities accountable for by a multifactorial combination of patient, provider and healthcare system factors.Methods and analysisData will be derived from the Vitamin D and Omega-3 Trial-Depression Endpoint Prevention (VITAL-DEP) study, a late-life depression prevention ancillary study to the VITAL trial. A total of 25 871 men and women, aged 50+ and 55+ years, respectively, were randomised in a 2×2 factorial randomised trial of heart disease and cancer prevention to receive vitamin D and/or fish oil for 5 years starting from 2011. Most participants were aged 65+ years old at randomisation. Medicare claims data for over 19 000 VITAL/VITAL-DEP participants were linked to conduct our study.The major study outcomes are depression treatment (antidepressant use and/or receipt of psychotherapy services) and adherence to medication treatment (antidepressant adherence and acceptability). The National Academy of Medicine framework for studying racial disparities was leveraged to select patient-level, provider-level and healthcare system-level variables and to address their potential roles in depression care disparities. Blinder-Oaxaca regression decomposition methods will be implemented to quantify and identify correlates of racial/ethnic disparities in depression treatment and adherence.Ethics and disseminationThis study received Institutional Review Board (IRB) approval from the Partners Healthcare (PHS) IRB, protocol# 2010P001881. We plan to disseminate our results through publication of manuscripts patient engagement activities, such as study newsletters regularly sent out to VITAL participants, and presentations at scientific meetings.Trial registration numberNCT01696435.

Depressive symptoms and low vitamin D status are common in older persons and may be associated, but findings are inconsistent. This study investigated whether 25-hydroxyvitamin D (25(OH)D) concentrations are associated with depressive symptoms in older adults, both cross-sectionally and longitudinally. We also examined whether physical functioning could explain this relationship, to gain a better understanding of the underlying mechanisms.Data from two independent prospective cohorts of the Longitudinal Aging Study Amsterdam were used: an older cohort (≥65 years, n = 1282, assessed from 1995-2002) and a younger-old cohort (55-65 years, n = 737, assessed from 2002-2009).Depressive symptoms were measured at baseline and after 3 and 6 years with the Center of Epidemiological Studies Depression Scale. Cross-sectional and longitudinal linear regression techniques were used to examine the relationship between 25(OH)D and depressive symptoms. The mediating role of physical functioning was examined in the longitudinal models.Cross-sectionally, associations were not significant after adjustment for confounders. Longitudinally, women in the older cohort with baseline 25(OH)D concentrations up to 75 nmol/L experienced 175 to 24% more depressive symptoms in the following 6 years, compared with women with 25(OH)D concentrations75 nmol/L. Reduced physical performance partially mediated this relationship. In men and in the younger-old cohort, no significant associations were observed.Older women showed an inverse relationship between 25(OH)D and depressive symptoms over time, which may partially be explained by declining physical functioning. Replication of these findings by future studies is needed.

PURPOSE: Associations between psychosocial factors and biomarkers are increasingly investigated in studies of cancer incidence and mortality. Documenting optimal data/biospecimen collection protocols and scale properties are fundamental for elucidating the impact of psychosocial factors on biologic systems and ultimately cancer development/progression. METHODS: Between 2013 and 2014, 233 Nurses’ Health Study II women (mean age: 60.6) participated in the Mind–Body Study. Participants completed a detailed online psychosocial assessment and provided hair, toenail, timed saliva over 1 day, urine and fasting blood twice, 1 year apart. Additionally, two separate microbiome collections for stool and saliva were conducted between the psychosocial assessments. We assessed correlations between various psychosocial measures and evaluated their 1-year reproducibility using intraclass correlations (ICC). RESULTS: Compliance with the protocols was high among participants. Psychosocial measures showed moderate-to-high reproducibility over 1 year (ICCs = 0.51–0.81). There was clear clustering of psychosocial factors according to whether they were querying positive (e.g., optimism, mastery, mindfulness) or negative (e.g., anxiety, depression, discrimination) emotion-related or social constructs. CONCLUSION: Results suggest feasibility for self-administered collection of various biospecimens and moderate-to-high reproducibility of psychosocial factors. The Mind–Body Study provides a unique resource for assessing inter-relationships between psychosocial factors and biological processes linked with long-term health outcomes, including carcinogenesis.

Experimental studies indicate that perinatal light exposure has enduring effects on affective behaviors in rodents; however, insufficient research has explored this hypothesis in humans. We examined photoperiod (i.e., day length) metrics during maternal pregnancy in relation to lifetime depression in the longitudinal Nurses’ Health Study (NHS) and NHS II. 160,723 participants reported birth date and birth state (used to derive daily photoperiod based on published mathematical equations), and clinician-diagnosed depression and antidepressant use throughout adulthood. Logistic regression was used to estimate odds ratios (OR) (and 95% confidence intervals [CI]) for depression (defined as clinician diagnosis and antidepressant use) across quintiles of two exposures during maternal pregnancy: 1) total photoperiod (total number of daylight hours) and 2) differences between minimum/maximum photoperiod; each trimester of pregnancy was examined separately. Total photoperiod during maternal pregnancy was not associated with depression overall or by trimester of pregnancy. However, larger differences between minimum/maximum photoperiod during maternal pregnancy were related to lower odds of depression (multivariable [MV]-adjusted OR: 0.86, 95% CI: 0.83, 0.90 comparing extreme quintiles of exposure; p-trend

BackgroundHomocysteine-lowering nutrients may have preventive/ameliorative roles in depression.AimsTo test whether long-term B-vitamin/folate supplementation reduces depression risk.MethodParticipants were 4331 women (mean age 63.6 years), without prior depression, from the Women's Antioxidant and Folic Acid Cardiovascular Study – a randomised controlled trial of cardiovascular disease prevention among 5442 women. Participants were randomly assigned to receive a combination of folic acid (2.5mg/d), vitamin B6 (50mg/d) and vitamin B12 (1 mg/d) or a matching placebo. Average treatment duration was 7 years. The outcome was incident depression, defined as self-reported physician/clinician-diagnosed depression or clinically significant depressive symptoms.ResultsThere were 524 incident cases. There was no difference between active v. placebo groups in depression risk (adjusted relative risk 1.02, 95% CI 0.86–1.21, P = 0.81), despite significant homocysteine level reduction.ConclusionsLong-term, high-dose, daily supplementation with folic acid and vitamins B6 and B12 did not reduce overall depression risk in mid-life and older women.

Objective: The aim of this study is to assess the utility of the Cogstate self-administered computerized neuropsychological battery in a large population of older men. Methods: We invited 7,167 men (mean age of 75 years) from the Health Professionals Follow-up Study, a prospective cohort of male health professionals. We considered individual Cogstate scores and composite scores measuring psychomotor speed and attention, learning and working memory and overall cognition. Multivariate linear regression was used to assess the association between risk factors measured 4 and 28 years prior to cognitive testing and each outcome. Results: The 1,866 men who agreed to complete Cogstate testing were similar to the 5,301 non-responders. Many expected risk factors were associated with Cogstate scores in multivariate adjusted models. Increasing age was significantly associated with worse performance on all outcomes (p < 0.001). For risk factors measured 4 years prior to testing and overall cognition, a history of hypertension was significantly associated with worse performance (mean difference of -0.08 standard units (95% CI -0.16, 0.00)) and higher consumption of nuts was significantly associated with better performance (>2 servings/week vs. Conclusions: The self-administered Cogstate battery showed significant associations with several risk factors known to be associated with cognitive function. Future studies of cognitive aging may benefit from the numerous advantages of self-administered computerized testing.

Low subjective cognitive function (SCF), which is associated with APOE4 genotype, adversely impacts quality of life and has predicted clinical dementia. We examined whether physical activity during early adulthood or mid-to-late life is associated with late-life SCF. We followed 28,481 US male health professionals aged 40–75 years who reported their physical activity in 1986 and biennially thereafter. SCF was reported in 2008 and 2012. The SCF score was averaged for the 2008 and 2012 assessments and categorized as “good”, “moderate”, and “poor”. Men in the highest versus lowest quintile of mid-to-late life physical activity in 1986 had 38% lower odds of poor versus good SCF score (multivariable-adjusted odds ratio (OR) 0.62; 95% CI 0.53, 0.72; P for trend

The reduction in cardiovascular disease (CVD) burden during the past half-century is one of the greatest public health successes in history.1 However, the gains in cardiovascular health have not been experienced equally across all groups. In addition to disparities by socioeconomic status, age, and race/ethnicity,1 differences by sex are also apparent.2 Overall reductions in CVD risk, as well as potential for benefit from existing cardioprotective strategies, seem greater among men than women.2 In addition, the clinical presentations of and several risk factors for CVD demonstrate sexual dimorphism.2 Therefore, ongoing work in CVD risk research has focused on potential paths to achieving better outcomes for women. A promising area is the domain of psychosocial factors, which have been associated with multiple biological processes that may be directly relevant to development of CVD. In this issue of Circulation Research , Chang et al3 report on the association between a key psychosocial factor—social integration—with incidence of coronary heart disease (CHD) among midlife and older women. They report that women with the highest levels of social integration (measured by an index of both content and frequency of social interactions) had ≈50% lower risk of CHD when compared with those with the lowest levels of social integration. Interestingly, the differences were significant for both …

Despite an extensive literature on the role of inflammation and depression, few studies have evaluated the association between inflammatory biomarkers and depression in a prospective manner, and results are inconclusive.We conducted a prospective analysis of blood levels of CRP, IL-6 and TNFα-R2 in 4756 women participating in the Nurses׳ Health Study who donated blood in 1990 and were depression-free up to 1996. Participants were followed between 1996 and 2008 for reports of clinical diagnosis depression or antidepressant use. Additionally, we conducted cross-sectional analyses for CRP, IL-6 and TNFα-R2 and antidepressant use at time of blood draw.After adjustment for body mass index, menopause status, use of anti-inflammatory drugs and other covariates, no significant associations between CRP, IL-6 and TNFα-R2 and incident depression were observed after a follow-up of 6-18 years. However, menopause status appears to modify the association between IL-6 and depression risk. In cross-sectional analyses, TNFα-R2 was associated with antidepressant use (OR=1.96, 95% CI=1.23-3.13, P-trend=0.001), but no significant associations were found for CRP and IL-6.Depression diagnosis was first assessed in 1996, 6 years after blood draw. However the biomarkers have high within-person correlations with measurements 4 years apart.Blood levels of CRP, IL-6 and TNFα-R2 were not associated with incident depression over a follow-up of 6-18 years. In cross-sectional analyses, antidepressant use may be associated with higher levels of TNFα-R2 but no associations with depression or antidepressant use were observed in the prospective analysis.

Intake of n-3 and n-6 polyunsaturated fatty acids (PUFAs) has been implicated in the pathogenesis of depression. We sought to estimate the association between intake of fish and n-3 and n-6 PUFAs and suicide mortality over the course of long-term follow-up. In this prospective cohort study, biennial questionnaires were administered to 42,290 men enrolled in the Health Professionals Follow-up Study (1988–2008), 72,231 women enrolled in the Nurses' Health Study (1986–2008), and 90,836 women enrolled in Nurses' Health Study II (1993–2007). Dietary fish and n-3 and n-6 PUFA intakes were assessed every 4 years using a validated food-frequency questionnaire. Suicide mortality was ascertained through blind physician review of death certificates and hospital or pathology reports. Adjusted relative risks of suicide mortality were estimated with multivariable Cox proportional hazards models and pooled across cohorts using random-effects meta-analysis. The pooled multivariable relative risks for suicide among persons in the highest quartile of intake of n-3 or n-6 PUFAs, relative to the lowest quartile, ranged from 1.08 to 1.46 for n-3 PUFAs (Ptrend = 0.11–0.52) and from 0.68 to 1.19 for n-6 PUFAs (Ptrend = 0.09–0.54). We did not find evidence that intake of n-3 PUFAs or fish lowered the risk of completed suicide.

Importance Measurement of delirium severity has been recognized as highly important for tracking prognosis, monitoring response to treatment, and estimating burden of care for patients both during and after hospitalization. Rather than simply rating delirium as present or absent, the ability to quantify its severity would enable development and monitoring of more effective treatment approaches for the condition. Objectives To present a comprehensive review of delirium severity instruments, conduct a methodologic quality rating of the original validation study of the most commonly used instruments, and select a group of top-rated instruments. Evidence Review This systematic review was conducted using literature from Embase, PsycINFO, PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature, from January 1, 1974, through March 31, 2017, with the key wordsdelirium,severity,tests,measures, andintensity. Inclusion criteria were original articles assessing delirium severity and using a delirium-specific severity instrument. Final listings of articles were supplemented with hand searches of reference listings to ensure completeness. At least 2 reviewers independently completed each step of the review process: article selection, data extraction, and methodologic quality assessment of relevant articles using a validated rating scale. All discrepancies between raters were resolved by consensus. Findings Of 9409 articles identified, 228 underwent full text review, and we identified 42 different instruments of delirium severity. Eleven of the 42 tools were multidomain, delirium-specific instruments providing a quantitative rating of delirium severity; these instruments underwent a methodologic quality review. Applying prespecified criteria related to frequency of use, methodologic quality, construct or predictive validity, and broad domain coverage, an expert panel used an iterative modified Delphi process to select 6 final high-quality instruments meeting these criteria: the Confusion Assessment Method–Severity Score, Confusional State Examination, Delirium-O-Meter, Delirium Observation Scale, Delirium Rating Scale, and Memorial Delirium Assessment Scale. Conclusions and Relevance The 6 instruments identified may enable accurate measurement of delirium severity to improve clinical care for patients with this condition. This work may stimulate increased usage and head-to-head comparison of these instruments.