Association of Physical Activity With Bioactive Lipids and Cardiovascular Events.

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 <0.1). Annotations were found for 6 of these BALs: 12,13-diHOME, 9,10-diHOME, lysoPC(15:0), oxymorphone-3b-D-glucuronide, cortisone, and oleoyl-glycerol. Genetic analysis within JUPITER-NC showed associations of 32 PA-related BALs with 22 single-nucleotide polymorphisms. From PA-related BALs, 12 are associated with CVD. CONCLUSIONS: We identified a PA-related bioactive lipidome profile out of which 12 BALs also had opposite associations with incident CVD events.

Association between number of Adverse Childhood Experiences and depression among older adults is moderated by race.

OBJECTIVE: This study aimed to assess the association between number of Adverse Childhood Experiences (ACE) and history of depression among older adults and to explore the interaction by race. METHODS: This study was a cross-sectional analysis of the 2020 Behavioral Risk Factor Surveillance System (BRFSS) data among 60,122 older respondents (≥ 60 years old). The ACE score (zero, one, two-three, ≥four) included questions assessing exposure to eight types of ACEs before age 18. The outcome was the respondent's self-report depression diagnosed (yes/no). Multivariable logistic regression models examined the association between ACEs and depression stratified by race. Each model adjusted for age, smoking status, income, education, marital status, and body mass index. RESULTS: In this sample of older adults, 47%, 23%, 19% and 10% reported having experienced zero, one, two-three, and four or more types of ACEs, respectively. Depression was reported by 16% of survey respondents. There was a significant interaction between ACE score and race and depression (p = 0.038). Respondents who experienced ≥4 ACEs had higher likelihood of reporting depression for all race/ethnicity groups: non-Hispanic Whites (aOR = 3.83; 95% CI: 3.07, 4.79), non-Hispanic Blacks (aOR = 3.39, 95% CI: 1.71, 6.71), or Hispanics (aOR = 12.61; 95% CI: 4.75, 33.43). This translated to a large effect size for non-Hispanic Whites and Hispanics although the magnitude was bigger for Hispanics. CONCLUSION: The association between number of ACEs and depression was strongest for older adults who identify as Hispanic, but weaker and less consistent for adults who identify as White and Black.

Projection of Care Partners' Preferences in the Proxy Assessments of Everyday Preferences for Persons With Cognitive Impairment.

OBJECTIVE: Bias in surrogate decision-making can occur when proxy decision-makers overestimate the degree to which their preferences are shared by others, resulting in a projection of their beliefs onto others. The purpose of this study is to assess projection of care partners' preferences onto surrogate assessments of everyday preferences for persons with cognitive impairment (CI) and to address clinical and demographic factors as predictors of projection. METHODS: The sample included 116 dyads of persons with CI (Clinical Dementia Rating Scale score ≥ 0.5) and their care partners. The Preferences for Everyday Living Inventory (PELI) was used to assess importance of preferences among persons with CI. Care partners completed two separate PELI assessments: one from the perspective of the persons with CI (i.e., acting as a surrogate decision-maker) and one from their own perspective. To assess for projection of care partners' preferences onto surrogate assessments of preferences for persons with CI, two-step regression with multivariable-adjusted general linear models was used. RESULTS: Significant projection was noted within the PELI domains of autonomous choice, personal growth, and keeping a routine (p < 0.005). More significant cognitive impairment was associated with increased projection within the PELI domains of autonomous choice and personal growth (p < 0.05). CONCLUSION: The results of this study suggest that projection of care partners' own preferences may be a significant source of bias in proxy decision-making regarding everyday preferences for persons with CI, particularly for those with more significant CI.

Potential impact of the COVID-19 pandemic on everyday preferences for persons with cognitive impairment.

The COVID-19 pandemic and subsequent social distancing guidelines and restrictions brought on changes in the everyday experiences of older adults. It is not clear, however, to what extent the pandemic has impacted the importance of everyday preferences for persons with cognitive impairment (CI) or the proxy ratings of those preferences. The sample of this study included 27 dyads of persons with CI and their care partners. The Preferences for Everyday Living Inventory was used to assess importance of preferences among persons with CI; care partners completed concurrent proxy assessments. Mixed random and fixed effects longitudinal models were used to evaluate changes in ratings and concordance levels between persons with CI and care partners prior to and during the COVID-19 pandemic. Persons with CI rated autonomous choice preferences as significantly more important during the COVID-19 pandemic than before; there was no association between the COVID-19 pandemic and change in other everyday preferences domains or discrepancy in proxy assessments of everyday preferences. Identifying avenues to support and provide for autonomy in the decision-making of older adults with CI may offer a way forward in mitigating the psychological and behavioral impacts of the COVID-19 pandemic in this population.

Re-remembering the influence of randomized ß-carotene on cognitive decline.

The wave of individuals impacted by dementia continues to rise rapidly as worldwide lifespan increases. Dietary strategies to slow cognitive decline and prolong time to clinical dementia remain understudied, but with potentially powerful public health consequences. Indeed, previously conducted large, randomized, placebo-controlled trials of micronutrients remain an under-leveraged resource to study changes in cognitive performance. As a motivating example, we highlight an ancillary report from the Physicians' Health Study, where subjects randomized to ß-carotene (a provitamin A carotenoid) had a more attenuated change in longitudinal global cognitive performance and verbal memory, as compared to subjects randomized to placebo. Despite mechanistic evidence from cell and animal studies supporting a vitamin A-mediated role in the biology associated with cognition, limited follow-up work has been conducted. We argue that dietary factors (including provitamin A) deserve a second look, leveraging multi-omic approaches, to elucidate how they may mitigate cognitive decline and dementia risk.

Child Maltreatment Among Older Adults: A Narrative Review of Psychotherapeutic Interventions and Clinical Considerations.

OBJECTIVES: The goals of this narrative review are to review the literature on psychotherapeutic interventions for older adults with histories of child maltreatment (CM) and to examine the unique considerations for assessing, diagnosing, and treating older adults with CM histories. METHODS: Online database searches were conducted to identify the extant research into the efficacy of psychotherapeutic interventions for older adults with CM-related trauma. RESULTS: Eight studies met inclusion criteria. The primary target diagnoses were post-traumatic stress disorder and depression. Psychotherapeutic interventions included Narrative Exposure Therapy, exposure-based treatments, Life Review Therapy, integrated treatments, and a spiritually-focused group therapy. CONCLUSIONS: While limited in number and generalizability due to study design and sample size and characteristics, the studies provide preliminary evidence of potentially effective psychotherapeutic treatments for older adults with CM histories. Further research is needed to determine the most effective psychotherapeutic interventions for this population. CLINICAL IMPLICATIONS: Many older adults suffer for decades with the repercussions of CM. Due to knowledge gaps regarding best practices for treating older adults with CM histories, many clinicians are poorly equipped to treat this population. Therefore, awareness of CM-related pathology and familiarity with effective psychotherapeutic interventions are essential for clinicians to meet the needs of this population.

Geographic Region, Racial/Ethnic Disparities, and Late-Life Depression: Results From a Large US Cohort of Older Adults.

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 versus 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 versus non-Hispanic whites had greater than 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.

Longitudinal Changes in Neuropsychiatric Symptoms: Impact of Discrepancy in Everyday Preferences Between Persons With Cognitive Impairment and Their Care Partners.

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.

Dispositional optimism and depression risk in older women in the Nurses´ Health Study: a prospective cohort study.

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.

Predictors of the importance of everyday preferences for older adults with cognitive impairment.

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.

Longitudinal differences in everyday preferences: Comparisons between people with cognitive impairment and their care partners.

OBJECTIVES: Persons with progressive cognitive impairment (CI) increasingly rely on surrogate decision-makers for everyday activities. Yet, little is known about changes in everyday preferences over time or about concordance between persons with CI and their care partners regarding longitudinal changes. METHODS: The sample included 48 dyads of persons with CI (Clinical Dementia Rating Scale score ≥0.5) and their care partners. The Preferences for Everyday Living Inventory was used to assess importance of preferences among persons with CI at baseline and follow-up (mean 486 days). Care partners separately completed concurrent proxy assessments. Mixed random and fixed effects longitudinal models were used to evaluate changes in ratings and concordance levels between persons with CI and care partners. RESULTS: There were significant gender differences regarding importance ratings of "autonomous choice" and "social engagement" preferences over time: women with CI rated these preferences as more important across time as a whole. Higher levels of neuropsychiatric symptoms were associated with less importance of "social engagement" preferences across time as a whole for persons with CI and a more negative discrepancy between persons with CI and care partner proxy assessments as time went on. CONCLUSION: This study yields new insights into predictors of longitudinal change in everyday preferences among persons with CI and their care partners. Although preferences were largely stable over time, there is increasing support for the relationship between differences in "social engagement" preferences and neuropsychiatric symptoms, which may have implications for monitoring and/or treatment in the context of cognitive impairment.

Telomere length and its relationships with lifestyle and behavioural factors: variations by sex and race/ethnicity.

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 < 0.01). Higher physical activity was associated with longer RTL (P-trend = 0.03); daily versus never/rare alcohol consumption and 30+ versus <5 smoking pack-year were associated with shorter RTLs (P-trend = 0.02). Associations varied significantly by sex and race/ethnicity. The association between physical activity and longer RTL appeared strongest among non-Hispanic Whites (P-interaction = 0.01). Compared to men, women had stronger associations between heavy smoking and shorter RTLs (P-interaction = 0.03). Light/moderate alcohol consumption (monthly/weekly) was associated with longer RTL among non-Hispanic Whites, while daily consumption was related to shorter RTLs among Blacks and Hispanics (P-interactions < 0.01). Associations of daily alcohol and heavy smoking with shorter RTLs were particularly apparent among Black women. 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.

Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial.

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 D3 (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.

Long-Term Intake of Dietary Carotenoids Is Positively Associated with Late-Life Subjective Cognitive Function in a Prospective Study in US Women.

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 < 0.001) for moderate SCF and 0.67 (95% CI: 0.60, 0.75; P-trend < 0.001) for poor SCF. This lower OR was also seen for carotenoids consumed 28 y before SCF assessment. Similar associations were found for total ß-carotene, dietary ß-carotene, α-carotene, lycopene, lutein + zeaxanthin, and ß-cryptoxanthin. The significant associations for ß-cryptoxanthin, lycopene, and lutein + zeaxanthin persisted after mutual adjustment for each other. CONCLUSIONS: Our findings support a long-term beneficial role of carotenoid consumption on cognitive function in women.

Differences in Assessment of Everyday Preferences Between People With Cognitive Impairment and Their Care Partners: The Role of Neuropsychiatric Symptoms.

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.

Changes in plant-based diet quality and health-related quality of life in women.

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.

Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial.

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 D3 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 D3 (2000 IU/d of cholecalciferol) and fish oil or placebo; 9181 were randomized to vitamin D3 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 D3 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 D3 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 D3 in adults to prevent depression. Trial Registration: ClinicalTrials.gov Identifiers: NCT01169259 and NCT01696435.

The Mind-Body Study: study design and reproducibility and interrelationships of psychosocial factors in the Nurses' Health Study II.

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.

Social Integration, Marital Status, and Ovarian Cancer Risk: A 20-Year Prospective Cohort Study.

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.

The relation of telomere length at midlife to subsequent 20-year depression trajectories among women.

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.