The United States Health and Human Services (HHS) and the United States Department of Agriculture (USDA) issued new alcohol guidelines in January 2026. The prior per occasion drinking limits of no more than 2 drinks per day for men and no more than 1 drink per day for women were replaced with the ambiguous advice to ‘consume less for better health’. Alcohol use remains one of the leading causes of preventable disease and death, contributing annually to 3 million deaths worldwide. Women have demonstrated recent increases in drinking and evidence exacerbated health risks associated with drinking alcohol. The removal of sex-specific drinking guidelines has significant health consequences, particularly for women. This Personal View addresses recent conflicting reports regarding the relationship between alcohol and health; summarizes the current state of the knowledge regarding alcohol and health; addresses women as a special population; and provides recommendations to improve public health.

Systematic review to identify the most promising experimental approaches to modify prenatal alcohol and cigarette use published since 2019. 20 studies met review criteria. Among the five approaches to prenatal alcohol use, a study comparing brief intervention or brief advice to treatment as usual in Argentina, and a practice change intervention to include evidence-based assessment and intervention of prenatal alcohol use in Australia were noteworthy. Five different strategies to modify cigarette use included diverse samples and settings. An innovative approach that was rigorously evaluated was conducted in Hong Kong where an intervention with brief advice, a nicotine sample, and active referral to smoking cessation service resulted in doubling the odds of biochemically validated abstinence from nicotine in expectant fathers when compared to an attention control condition. Prenatal alcohol and cigarette smoking are common in the US and pending effective intervention strategies that may be informed by international research.

BACKGROUND:Gender-related disparities in access to alcohol-related care exist in the Department of Veterans Affairs' (VA) health care system. Understanding differences in the use of alcohol-related care in the context of potentially important covariates (e.g., race, ethnicity, younger age, and military sexual trauma [MST]) is critical to support the health and well-being of women Veterans. This study examined differences in the use of alcohol preventive care among women Veterans. METHODS:From VA administrative data (2010-2016), we drew a sample of women Veterans (n = 280) who screened positive for at-risk drinking in inpatient/outpatient settings. We conducted a chart review to abstract variables from the medical record. Then, we employed logistic regression to predict receipt of any follow-up (brief intervention and/or referral to treatment) and initiation of treatment, as with covariates of race, ethnicity, age, and clinical characteristics such as MST. RESULTS:Seventy-four percent (n = 207) of the sample received any follow-up. Of those referred to treatment (n = 115), 73% (n = 84) initiated treatment. Hispanic women were 71% less likely to receive follow-up care than non-Hispanic women. Women Veterans 21 to 24 years were less likely to initiate treatment than those 25 to 29 years. While women Veterans who endorsed MST were more likely to receive follow-up care than others, they were no more likely to initiate treatment. CONCLUSIONS:Given the rapid growth of the women Veteran population, their access to alcohol-related care is vital. Without culturally competent, clinically and developmentally appropriate alcohol prevention messaging for Hispanic and younger women Veterans with trauma, differences in access to care and disparities in outcomes will persist.

There is an urgent need to identify novel, accessible and affordable strategies to prevent cognitive decline and progression in the Alzheimer disease and related dementias (ADRD) continuum. Vitamin D3 and marine omega-3 fatty acids (omega-3s) supplements show promise for cognitive protection, with potential variations in their effects by sex or race. However, to date, no randomized clinical trials (RCTs) have tested their impact on emerging plasma-based biomarkers with potential utility to predict ADRD pathogenesis. Vitamin D and Omega-3 Trial (VITAL) is a completed, nation-wide, 2x2 factorial placebo-controlled RCT testing vitamin D3 (2000 IU/d) and omega-3s (1 g/d) for cancer and cardiovascular disease prevention. We included a Boston-area sub-cohort of 929 randomized VITAL participants who provided blood samples at baseline, 2-year, and/or 4-year follow-up. Plasma ADRD biomarkers, including an N-terminal tau fragment (NT1), amyloid-β (Aβ)-40, Aβ-42, neurofilament-light (NfL), and glial fibrillary acidic protein (GFAP), were measured. We used multivariable-adjusted repeated measures models for data analysis; sex and race were pre-specified effect modifiers. Among 929 participants, the mean age was 65 years; 49.2% were females; 17.3% were from racial and/or ethnic minority backgrounds, including 8.2% Black adults. Neither vitamin D3 nor omega-3s, compared to placebo, significantly reduced ADRD biomarkers overall across 4 years of treatment; however, there was a trend for reduction in Aβ-40:Aβ-42 ratio over 4 years for vitamin D3 versus placebo [percent difference (95% confidence interval [CI]): -1.2 (-2.7, 0.3)]. Subgroup analyses uncorrected for multiple-testing suggested interactions by sex and race. Vitamin D3 versus placebo resulted in a reduction in NT1 among males (-2.7%) but not females (p-interaction=0.08). Among Black participants, vitamin D3 versus placebo resulted in a 16% reduction in NfL levels [95% CI, -30.5% to 1.1%; p-interaction=0.06], while omega-3s versus placebo showed a 12.4% reduction in GFAP levels [95% CI, -21.5% to -2.2%; p-interaction=0.049]. In this RCT sub-cohort of 929 older adults, neither vitamin D3 nor omega-3s supplements significantly reduced selected plasma ADRD biomarkers over 4 years. We observed potential differences by sex and race in reductions of some ADRD biomarkers in response to these supplements which warrant further investigation in a larger sample.

Importance: Despite increased initiatives and funding to improve access to evidence-based treatments for opioid use disorder (OUD), including medications for OUD (mOUD), pregnant/postpartum individuals have significant obstacles to accessing these life-saving medications.Observations: Current legislation, specifically the Comprehensive Addiction and Recovery Act (CARA), mandates that the Governor of each state has systems in place to identify and address the needs of substance-exposed infants. However, this legislation removed the word "illegal" when defining substance use and left other important words in the law up to each individual state to define. These changes resulted in pregnant/postpartum individuals with OUD who were receiving legally prescribed mOUD, being subject to legal actions. In many states, such notifications result in investigation and punitive actions, which may include the removal of children from the care of postpartum individuals. These state policies have created additional barriers to accessing mOUD for pregnant and/or postpartum individuals. Research has demonstrated that pregnant individuals delay and/or avoid recommended prenatal care or decide to stop taking mOUD altogether, to prevent potential legal and child welfare-related consequences. This situation is problematic as it places individuals at risk of overdose and death and infants at risk of health complications. Importantly, such policies are subject to bias and disproportionately impact individuals of color and those from lower socioeconomic backgrounds.Conclusions and Relevance: The need to address and change the criminalization of pregnant/postpartum substance use laws to not penalize individuals adhering to the recommended standard of evidence-based care is urgent. Specific recommendations include: not relying on toxicology testing, reinstating "illegal/non-prescribed" language in legislation, implementing Plans of Safe Care, use of a two "track" reporting system, and federal support for states complying with Child Abuse Prevention and Treatment Act Reauthorization of 2010 (CAPTA) laws, increasing resources to improve outcomes for infants/postpartum individuals with OUD, and additional mandated training to educate key individuals, such as hospital/outpatient clinic providers and child-welfare workers.

Objective: The United States Veterans Health Administration My Life, My Story (MLMS) program is a patient-centered care intervention where veterans are interviewed about their life story and may grant permission to include it in their electronic health record (EHR). Our purpose was to focus on a sample of MLMS narratives from veterans with self-disclosed substance use (SU) from our institution, and to evaluate the potential relationship between their content and a life change for the better, and to compare their content with the EHR. Methods: The narratives were reviewed on 4 domains (past challenge, substance use, experience of a turning point or insight, life improvement) by two reviewers using a pre-specified code book. 31 narratives were reviewed. Additional demographic and clinical data were abstracted from the EHR. Results: Veterans' mean age was 68.7 (SD = 6.0) years when interviewed. All were male and had a tobacco (23%), SU (45%), anxiety (32%), mood (45%), or post-traumatic stress (32%) problem on EHR review. 48% received outpatient mental health treatment whereas 24% received outpatient SU treatment. With regards to MLMS content, 74.2% described a significant life stressor, 93% confirmed SU, 71% reported a turning point, and 80.7% had experienced life improvement. There were no statistically significant relationships between the EHR data and MLMS content areas. However, when a turning point was described, the odds of having a life improvement were increased 26-fold (OR = 26.2, 95% CI = 2.4, 288.9, c-statistic = 0.84). Conclusion: The MLMS narrative from the veterans' perspective provides additional richness to their history unavailable in the EHR.

Background: Assignment of fiduciaries to veterans with disability payments is an intervention thought to improve quality of life; however, in veterans who use substances, a proportion of these payments may be misspent on drugs and/or alcohol. While fiduciary assignment may reduce funds available to purchase substances, clinical efficacy of this intervention in the management of substance use disorders has not been rigorously demonstrated.Objectives: The purpose of this study is to evaluate changes in clinical status before and after fiduciary assignment.Methods: This was a retrospective chart review of 50 (44 male, 6 female) veterans who were assigned a fiduciary and determined to have a substance use disorder (SUD). SUD-related data including outpatient and inpatient treatment, toxicology testing, and measures of psychosocial functioning for the three years before and after fiduciary assignment were extracted and compared.Results: Veterans were found to have higher rates of any form of employment after fiduciary assignment (Wilcoxon, Signed Ranked S-statistic = 0.22, pr = 0.02). Two changes in measures of substance use were found after fiduciary assignment. There was a reduction in positive screens for heroin (tstatistic = -2.7, p = .01), but an increase in positive screens for fentanyl (t statistic = 2.53, p = .02). There were some potentially clinically but not statistically significant trends in increased adherence with mental health appointments, number of medical hospitalizations, and rates of employment post-fiduciary assignment.Conclusions: Understanding the clinical impact of fiduciary assignment for veteran's benefits is desirable but still pending at this time.

BACKGROUND Apolipoprotein E (APOE)-ε4 allele is associated with cognitive decline; however, its potential to modify effects of vitamin D3 and omega-3s supplementation on later-life cognition is unclear. Our objectives were to estimate among the in-clinic subset of a randomized trial: 1) associations between APOE-ε4 and global and domain-specific cognitive change, with exploration of potential sex and race differences; 2) modification by APOE-ε4 of effects of vitamin D3 and omega-3s supplementation on cognitive change. METHODS From an ancillary study of depression prevention within a completed 2x2 factorial trial testing vitamin D3 (2000 IU/d), omega-3s (1 g/d), and/or placebos, we included 743 older adults with baseline in-person neuropsychiatric assessments and APOE genotyping data. The primary outcome was change in global cognition (averaging z-scores of 9 tests) over 2 years. Secondarily, episodic memory and executive function/attention z-scores were examined. General linear models of response profiles with multiplicative interaction terms were constructed; stratified results were reported. RESULTS Mean age (standard deviation) was 67.1 (5.3) years; 50.6% were females; 24.9% were APOE-ε4 carriers. Compared to non-carriers, APOE-ε4 carriers had worse 2-year change in global cognition and episodic memory; differences were more apparent among females than males. There was no variation by race in APOE-ε4 associations with cognition. APOE-ε4 did not significantly modify effects of vitamin D3 or omega-3s, compared to placebo, on change in global cognition, episodic memory, or executive function/attention. CONCLUSION APOE-ε4 was associated with worse cognition but did not modify overall effects of vitamin D3 or omega-3 supplementation on cognition over 2 years.

Objective: To test vitamin D3 and omega-3 fatty acids (omega-3s) for late-life depression prevention under the National Academy of Medicine framework for indicated (targeting subthreshold depression) and selective (targeting presence of high-risk factors) prevention. Methods: The VITamin D and OmegA-3 TriaL (VITAL) is a 2 × 2 factorial trial of vitamin D3 (2,000 IU/d) and/or omega-3s (1 g/d) for cardiovascular and cancer prevention (enrollment: November 2011-March 2014; end date: December 31, 2017). In this targeted prevention study, we included 720 VITAL clinical sub-cohort participants who completed neurobehavioral assessments at baseline and 2 years (91.9% retention). High-risk factors were subthreshold or clinical anxiety, impaired activities of daily living, physical/functional limitation, medical comorbidity, cognitive impairment, caregiving burden, problem drinking, and low psychosocial support. Coprimary outcomes were incident major depressive disorder (MDD), adjudicated using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), and change in mood (Patient Health Questionnaire-9 [PHQ-9]). We used exact tests to determine treatment effects on MDD incidence and repeated-measures models to determine treatment effects on PHQ-9. Results: A total of 11.1% had subthreshold depression, 60.8% had ≥ 1 high-risk factor, MDD incidence was 4.7% (5.1% among completers), and mean PHQ-9 score change was 0.02 points. Among those with subthreshold depression, the MDD risk ratio (95% confidence interval) was 0.36 (0.06 to 1.28) for vitamin D3 and 0.85 (0.25 to 2.92) for omega-3s, compared to placebo; results were also null among those with ≥ 1 high-risk factor (vitamin D3 vs placebo: 0.63 [0.25 to 1.53]; omega-3s vs placebo: 1.08 [0.46 to 2.71]). There were no significant differences in PHQ-9 score change comparing either supplement with placebo. Conclusions: Neither vitamin D3 nor omega-3s showed benefits for indicated and selective prevention of late-life depression; statistical power was limited. Trial Registration: ClinicalTrials.gov identifier: NCT01696435.

Objective: To test vitamin D3 and omega-3 fatty acids (omega-3s) for late-life depression prevention under the National Academy of Medicine framework for indicated (targeting subthreshold depression) and selective (targeting presence of high-risk factors) prevention. Methods: The VITamin D and OmegA-3 TriaL (VITAL) is a 2 í 2 factorial trial of vitamin D3 (2,000 IU/d) and/or omega-3s (1 g/d) for cardiovascular and cancer prevention (enrollment: November 2011–March 2014; end date: December 31, 2017). In this targeted prevention study, we included 720 VITAL clinical sub-cohort participants who completed neurobehavioral assessments at baseline and 2 years (91.9% retention). High-risk factors were subthreshold or clinical anxiety, impaired activities of daily living, physical/functional limitation, medical comorbidity, cognitive impairment, caregiving burden, problem drinking, and low psychosocial support. Coprimary outcomes were incident major depressive disorder (MDD), adjudicated using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), and change in mood (Patient Health Questionnaire-9 ). We used exact tests to determine treatment effects on MDD incidence and repeated-measures models to determine treatment effects on PHQ-9. Results: A total of 11.1% had subthreshold depression, 60.8% had ≥ 1 high-risk factor, MDD incidence was 4.7% (5.1% among completers), and mean PHQ-9 score change was 0.02 points. Among those with subthreshold depression, the MDD risk ratio (95% confidence interval) was 0.36 (0.06 to 1.28) for vitamin D3 and 0.85 (0.25 to 2.92) for omega-3s, compared to placebo; results were also null among those with ≥ 1 high-risk factor (vitamin D3 vs placebo: 0.63 ; omega-3s vs placebo: 1.08 ). There were no significant differences in PHQ-9 score change comparing either supplement with placebo. Conclusions: Neither vitamin D3 nor omega-3s showed benefits for indicated and selective prevention of late-life depression; statistical power was limited. Trial Registration: ClinicalTrials.gov identifier: NCT01696435 J Clin Psychiatry 2023;84(4):22m14629 Author affiliations are listed at the end of this article.

This study: 1) examined cross-sectional and longitudinal relations of serum brain-derived neurotrophic factor (BDNF) to late-life depression (LLD); 2) tested effects of vitamin D3 and omega-3s on change in BDNF; 3) explored modifying or mediating roles of BDNF on effects of vitamin D3 and omega-3s for LLD. We selected 400 adults from a completed trial of vitamin D3 and omega-3 supplements for LLD prevention. BDNF was measured using an enzyme-linked immunosorbent assay. We administered semi-structured diagnostic interviews and Patient Health Questionnaire [PHQ]-9 to ascertain outcomes at baseline (depression caseness vs. non-caseness; PHQ-9) and at 2-year follow-up among baseline non-depressed individuals (incident vs. no incident MDD; change in PHQ-9). At baseline, while there were no significant differences in mean serum BDNF comparing depression cases and non-cases, being in the lowest vs. highest serum BDNF quartile was significantly associated with worse depressive symptoms. There were no significant longitudinal associations between serum BDNF and LLD. Neither supplement significantly affected change in BDNF; serum BDNF did not appear to modify or mediate treatment effects on LLD. In conclusion, we observed significant cross-sectional but not longitudinal associations between serum BDNF levels and LLD. Vitamin D3 or omega-3s did not alter serum BDNF over 2 years.

ObjectiveSurvivorship guidelines recommend screening for depression and anxiety in young adult cancer survivors (YACS), but research validating measures in this population is limited. The current study aimed to examine use of the Primary Care Evaluation of Mental Disorders (PRIME-MD) to screen for depression and anxiety in YACS. Methods249 YACS (aged 18-40, 50% male) completed PRIME-MD via Telephone Automated Computer Assisted Structured Interview and the Structured Clinical Interview for the DSM-IV (SCID) via in-person interview. SCID responses were scored to identify depressive and anxiety symptoms and diagnoses. PRIME-MD was scored to identify YACS reaching the symptom threshold (>= 1 depressive or anxiety symptom) and diagnostic threshold for depressive or anxiety disorder. ROC analyses evaluated concordance of the PRIME-MD with the SCID. ResultsThe PRIME-MD depressive symptom threshold had excellent discrimination compared to SCID depressive diagnosis (AUC = 0.83) with high sensitivity (86%) and specificity (81%). Similarly, the PRIME-MD depressive diagnosis threshold had excellent discrimination compared to SCID depressive diagnosis (AUC = 0.86) as well as high sensitivity (86%) and specificity (86%). No PRIME-MD threshold met sensitivity (>= 0.85) and specificity (>= 0.75) criteria for identifying SCID depressive symptoms, anxiety disorders, or anxiety symptoms. ConclusionsPRIME-MD has potential utility as a screening measure of depressive disorders in YACS. The PRIME-MD depressive symptom threshold may be particularly useful in survivorship clinics as it requires only two items be administered. However, PRIME-MD does not meet study criteria for a standalone screen for anxiety disorders, anxiety symptoms, or depressive symptoms in YACS.

PURPOSE: This narrative review summarizes and synthesizes the clinical trials and randomized clinical trials that evaluated selected and targeted approaches to reducing preconception and prenatal alcohol exposure (PAE) and alcohol-exposed pregnancy (AEP) since 2011.SEARCH METHODS: A professional hospital librarian completed the primary search using strategies specified within this review, resulting in 94 records returned in PubMed, Ovid MEDLINE, Clinical Key, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The author completed two supplementary literature searches.SEARCH RESULTS: From the total of 238 records returned from the three searches, 217 records were eliminated. Elimination reasons included other medical problem (119); duplicate entry (34); no content/results (23); secondary analysis (16); focus on effects of PAE (9); treatment of childhood fetal alcohol spectrum disorders (FASD) (6); maternal risk factors (3); and other (7). The remaining 21 studies were included with four overarching themes: (1) case management efforts (n = 4); (2) preconception efforts to reduce AEP (n = 5); (3) motivational interviewing and screening, brief intervention, and referral to treatment (n = 2); and (4) use of technology to deliver the intervention (n = 10).DISCUSSION AND CONCLUSIONS: Case management and home visits did not appear to have strong current empirical support. Study limitations included small sample sizes and no comparison groups, whereas larger efforts did not demonstrate definitive advantages to justify this intensive approach. The studies of preconception efforts, all based on the Project CHOICES approach, had similar outcomes, with the reduction in AEP risk largely due to improved contraception in women of childbearing age who were sexually active and drank alcohol but were not pregnant. It is unknown whether these women refrained from alcohol use when they became pregnant. Two studies of motivational interviewing to reduce prenatal alcohol use did not demonstrate the efficacy of the intervention. Both were small, with less than 200 pregnant women combined; moreover, the study samples had low baseline levels of alcohol use, allowing little opportunity for improvement. Finally, studies evaluating the impact of technological approaches to reducing AEP were reviewed. These exploratory investigations had small sample sizes and provided preliminary evaluations of techniques such as text messages, telephone contact, computer-based screening, and motivational interviewing. The potentially promising findings may inform future research and clinical efforts. Future directions may include research to address the limitations of the evidence to date and should reflect the complexities of FASD that include the biological and social context associated with prenatal alcohol use.

Objective: The Diagnostic and Statistical Manual for Psychiatric Diagnoses (DSM-5) significantly narrowed conditions under which life-threatening illnesses meet qualifying traumatic event (QTE) criteria for posttraumatic stress disorder (PTSD). To investigate the impact of this change on identification of PTSD in young adult cancer survivors (YACS), we compared prevalence of QTE exposure using DSM-5 and earlier DSM-IV criteria.Methods: The Structured Clinical Interview for the DSM-5 (SCID-5) was customized for study goals and administered to a convenience sample of 250 YACS ages 18-40 followed at a single cancer center.Results: The SCID-5 was well-tolerated by participants and estimated duration was brief (33 min; range 12-75). Only 35 interviews (14%) presented complex scoring questions. 168 participants (67.2%) identified cancer as their "most stressful or traumatic experience." Applying DSM-IV criteria, 227 YACS (90.8%) reported any QTEs; prevalence was significantly reduced following more restrictive DSM-5 QTE criteria, with only 124 YACS (49.6%) reporting =1 QTE (z = -9.68, p < 0.001).Conclusions: The SCID-5 can be successfully adapted to assess QTEs in YACS following both DSM-IV and DSM-5 criteria. DSM-5 criteria significantly limit prevalence of QTE exposures compared with DSM-IV. As the majority of YACS identify cancer as their most stressful life event, it is critically important to investigate its impact on their psychological functioning. Until more is known about how PTSD symptoms may arise after cancer, clinicians and researchers should adapt PTSD assessments to systematically evaluate the role of cancer as a traumatic event that may lead to PTSD symptoms in YACS.

Objective: To test vitamin D3 and omega-3s for late-life depression prevention under the National Academy of Medicine framework for indicated (targeting subthreshold depression) and selective (targeting presence of high-risk factors) prevention. Methods: VITamin D and OmegA-3 TriaL (VITAL) is a 2x2 factorial trial of vitamin D3 (2000 IU/day) and/or omega-3s (1 g/day) for cardiovascular and cancer prevention (enrollment: November 2011-March 2014; end date: December 31, 2017). In this targeted prevention study, we included 720 VITAL clinical sub-cohort participants who completed neurobehavioral assessments at baseline and 2 years (91.9% retention). High-risk factors were: subthreshold or clinical anxiety, impaired activities of daily living, physical/functional limitation, medical comorbidity, cognitive impairment, caregiving burden, problem drinking, and low psychosocial support. Co-primary outcomes were: incident major depression (MDD), adjudicated using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4 th edition); change in mood (Patient Health Questionnaire-9 [PHQ-9]). We used exact tests to determine treatment effects on MDD incidence and repeated measures models to determine treatment effects on PHQ-9. Results: 11.1% had subthreshold depression, 60.8% had ≥1 high-risk factors, MDD incidence=4.7% (5.0% among completers), and mean PHQ-9 change=0.02 points. Among those with subthreshold depression, the MDD risk ratio (95% confidence intervals)=0.36 (0.06 to 1.28) for vitamin D3 and 0.85 (0.25 to 2.92) for omega-3s, compared to placebos; results were also null among those with ≥1 high-risk factors [vitamin D3 vs. placebo: 0.63 (0.25 to 1.53); omega-3s vs. placebo: 1.08 (0.46 to 2.71)]. There were no significant differences in PHQ-9 change comparing either supplement with placebo. Conclusion: Neither vitamin D3 nor omega-3s showed benefits for indicated and selective prevention of late-life depression; statistical power was limited.

Background: Associations between epigenetic aging with cognitive aging and neuropsychiatric measures are not well-understood. Objective: 1) To assess cross-sectional correlations between second-generation DNA methylation (DNAm)-based clocks of healthspan and lifespan (i.e., GrimAge, PhenoAge, and DNAm-based estimator of telomere length [DNAmTL]) and cognitive and neuropsychiatric measures; 2) To examine longitudinal associations between change in DNAm markers and change in cognition over 2 years. Methods: Participants were members of VITAL-DEP (VITamin D and OmegA-3 TriaL- Depression Endpoint Prevention) study. From previously ascertained cognitive groups (i.e., cognitively normal and mild cognitive impairment), we randomly selected 45 participants, aged≥60 years, who completed in-person neuropsychiatric assessments at baseline and 2 years. The primary outcome was global cognitive score (averaging z-scores of 9 tests). Neuropsychiatric Inventory severity scores were mapped from neuropsychiatric symptoms (NPS) from psychological scales and structured diagnostic interviews. DNAm was assayed using Illumina MethylationEPIC 850K BeadChip at baseline and 2 years. We calculated baseline partial Spearman correlations between DNAm markers and cognitive and NPS measures. We constructed multivariable linear regression models to examine longitudinal relations between DNAm markers and cognition. Results: At baseline, we observed a suggestive negative correlation between GrimAge clock markers and global cognition but no signal between DNAm markers and NPS measures. Over 2 years: each 1-year increase in DNAmGrimAge was significantly associated with faster declines in global cognition; each 100-base pair increase in DNAmTL was significantly associated with better global cognition. Conclusion: We found preliminary evidence of cross-sectional and longitudinal associations between DNAm markers and global cognition.

In a recent trial, we observed no effect of omega-3 fatty acids (omega-3s) supplementation on cognitive decline. However, brain concentrations and metabolism of lipid molecules in response to omega-3s may be regulated by apolipoprotein E (APOE)-ε4 allele status. Further, while APOE-ε4 is an established risk factor for Alzheimer disease, its association with cognitive decline is uncertain, especially in more diverse samples. The few randomized clinical trials (RCTs) addressing the moderation of effects of omega-3s on cognitive decline by APOE-ε4 have yielded inconsistent findings. Thus, we examined moderation by APOE-ε4 on effects of omega-3s vs. placebo for global and domain-specific cognitive change over 2 years in a well-characterized, diverse sample of older adults. VITamin D and OmegA-3 TriaL (VITAL) is a 2×2 factorial RCT of vitamin D3 (2000 IU/day) and/or omega-3s (1 g/day including 460 mg of eicosapentaenoic acid and 380 mg of docosahexaenoic acid) for cardiovascular disease and cancer prevention. We included 743 VITAL in-clinic sub-cohort participants who completed all cognitive tests at baseline and had APOE genotype data. The primary outcome was change in global cognition (averaging z-scores of 9 tests) over 2 years; episodic memory and executive function/attention were examined separately. We used multiplicative interaction terms in general linear models of response profiles to examine moderation by APOE-ε4 carrier status on effects of omega-3s vs. placebo for cognitive change outcomes over 2 years. The mean age (standard deviation) of participants was 67.1 (5.3) years; 50.6% were females; 13.5% were from racial and/or ethnic minority backgrounds; and 24.9% were APOE-ε4 allele carriers. Over 2 years, compared with APOE-ε4 non-carriers, APOE-ε4 carriers had faster declines in global cognition and episodic memory but not in executive function/attention; e.g., the mean difference in change (95% confidence interval) for episodic memory comparing APOE-ε4 carriers vs. non-carriers was -0.18 (-0.33 to -0.03). There were no significant interactions between APOE-ε4 carrier status and randomization status (omega-3s vs. placebo) on change in global, episodic memory, or executive function/attention scores. APOE-ε4 significantly predicted cognitive decline but did not modify the effect of omega-3s on global and domain-specific cognitive change over 2 years.

Patient-reported outcomes (PROs) are essential for assessing potential late effects experienced by young adult cancer survivors (YACS), but stigma and social desirability bias may limit their effectiveness for assessing sensitive topics (e.g., suicidal ideation, sexual health). This study compared two methods of item administration to determine the optimal method for obtaining sensitive information in YACS. Two hundred forty-four YACS (ages 18–40) were randomized to complete measures of suicidal ideation and sexual health (i.e., sensitive items) by paper survey or by telephone automated computer assisted structured interview (TACASI). Participants also provided information on acceptability of administration mode and sensitive items. The proportion of participants reporting symptoms did not significantly vary between paper and TACASI administration: respectively, 10

Background: Limited research exists on the association between substance use disorders (SUDs) and dimensions of pregnancy intention. This study sought to examine the independent relationships between prepregnancy substance use and SUDs with pregnancy timing and intentions. Materials and Methods: Secondary analysis of data from three prenatal care sites in Connecticut, Massachusetts, and Michigan, 2016-2017. Associations were estimated using modified Poisson regression with robust error variance to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs), controlling for relevant covariates. Results: The total sample size was 1115 women. Respectively, 61.1% and 15.5% of women used any substance in the 30 days prepregnancy or had any SUD in the past 12 months. After adjustment, any prepregnancy substance use was associated with a reduced likelihood of a well-timed (aPR 0.85; 95% CI: 0.77-0.93) and intended (aPR 0.80; 95% CI: 0.72-0.89) pregnancy; similarly, any SUD was associated with a reduced likelihood of a well-timed (aPR 0.66; 95% CI: 0.55-0.80) and intended (aPR 0.79; 95% CI: 0.67-0.93) pregnancy. Conclusions: Women with prepregnancy substance use or SUD have decreased prevalence of well-timed and intended pregnancies. Greater efforts are needed to address substance use and family planning in routine, well-woman, prenatal, and postpartum care.