Early Childhood Adversity Predicts Risk of Family Caregiver Suicidal Ideation:Roles of Neuroticism and Self-Compassion.

Background: Despite high rates of family caregiver suicidal ideation (SI), little is known about its relationship with childhood adversity. Those with a history of adverse childhood experiences (ACEs) have been shown to have higher neuroticism, lower self-compassion, and higher rates of late life mental health disorders. Caregiving for a family member with dementia may pose a particular challenge for those with ACEs. Methods: In a secondary analysis of 81 family caregivers of people living with dementia enrolled in clinical trials, we undertook a cross-sectional baseline analysis of the association between childhood adversity, measured with the ACE questionnaire, and self-reported suicidal ideation (SI). We further assessed whether the relationship between ACE and SI was mediated by neuroticism and self-compassion. Results: 18 caregivers self-reported SI (22%). 89% of caregivers with SI reported childhood adversity (ACE > 0), versus 63% of those without SI (p=.04). The relative risk of SI was 3.6x higher in those with childhood adversity than in those without (p=.04), and for those with a specific history childhood abuse, the relative risk of SI was 3.4x higher (p=.005). Neuroticism and self-compassion mediated the relationship between ACE and SI (p<.05), with neuroticism strengthening the association and self-compassion weakening it. Conclusions: The association of SI with history of childhood adversity is high in family caregivers. Whereas elevated neuroticism might be one mechanism linking ACEs and SI, training self-compassion is a promising target for reducing SI. The phenotypic relationship between childhood adversity and SI in family caregivers should be further explored in larger samples, and could represent a new treatment target to improve the efficacy of therapies on caregiver emotional symptoms.

Dietary patterns, inflammatory biomarkers and cognition in older adults: An analysis of three population-based cohorts.

BACKGROUND: Targeting effective strategies to prevent cognitive decline is key in the aging population. Some diets have been linked to a slower cognitive decline, potentially through reducing inflammation. We aimed at determining the effect of inflammatory dietary patterns (IDPs) on cognitive function in three population-based cohorts. METHODS: In this longitudinal study, we analyzed data from the Canadian Longitudinal Study of Aging, CoLaus|PsyCoLaus and Rotterdam Study. Our analytical sample included participants over 55 years old with baseline data on cognition, dietary intake, and inflammatory markers. IDPs were derived for each cohort using reduced rank regression to reflect maximal variation in three inflammatory markers. We calculated scores of consumption of the IDPs, higher scores indicating more IDP consumption. We used inverse probability of treatment and censoring weights in the marginal structural models to estimate associations of higher versus lower quarters of consumption of an IDP on general cognition (Mini-Mental State Evaluation) and four cognitive domains (memory, verbal fluency, verbal learning and processing speed and executive function) during at least 3 years of follow-up. RESULTS: We included 10,366 participants (mean age 68) followed-up for a mean of 5 years. Diet explained between 1 and 2% of the variation of the inflammatory markers. There were no differences in general cognition when comparing the highest to the lowest quarter of consumption of IDPs among the three cohorts. Mean differences for the four cognitive domains were of small magnitude across cohorts and not clinically relevant. CONCLUSION: Diet explained low variation in inflammatory markers. Consuming IDPs was not associated with mean differences in general or domain-specific cognitive function.

Pet Attachment and Anxiety and Depression in Middle-Aged and Older Women.

Importance: Understanding how attachment to pets can alleviate depression and anxiety offers valuable insights for developing preventive and therapeutic strategies, particularly for those with insecure attachment styles from childhood trauma. Objective: To determine if a close bond with a pet is associated with reduced depression and anxiety, especially among women who experienced childhood abuse. Design, Setting, and Participants: This cross-sectional study involved women who voluntarily enrolled in the Mind Body Study (MBS), a substudy of the Nurses' Health Study II (NHS2) focusing on psychosocial factors. Women reporting childhood abuse were oversampled to capture their psychosocial distress in adulthood. MBS participants were invited to complete comprehensive online questionnaires, which were administered twice (March 2013 and February 2014). Exposure: Pet attachment measured by Lexington Attachment to Pets Scale (LAPS). Main Outcomes and Measures: Levels of depression and anxiety (10-item Centre for Epidemiologic Studies Depression Scale [CESD-10]; Kessler Psychological Distress Scale [K6]; 7-item Generalized Anxiety Disorder scale [GAD-7]; Crown Crisp Experiential Index phobic anxiety subscale [CCI]), considered individually and combined into an overall z-score measure of anxiety and depression symptoms. Results: A total of 214 women (mean [SD] age, 60.8 [3.9] years) were included; 156 women (72.6%) reported a history of childhood abuse. Of 688 invited MBS participants in 2013, 293 (42.6%) expressed interest; there were 228 completed questionnaires (response rate, 77.8%) in 2013 and 208 questionnaires (response rate, 71.0%) in 2014. LAPS scores were provided by 140 participants (65.4%), 78 (55.7%) for dogs and 46 (32.9%) for cats. Overall higher pet attachment on the LAPS score was significantly associated with lower GAD-7 scores (ß = -0.17; 95% CI, -0.29 to -0.06), but there was no association for phobic anxiety or depression. There were no statistically significant associations between cat attachment and depression or anxiety. Higher dog attachment was associated with significantly lower scores in depression (CESD-10: ß, -0.47; 95% CI, -0.68 to -0.26; K6: ß = -0.42; 95% CI, -0.54 to -0.31), generalized anxiety (GAD-7: ß = -0.47; 95% CI, -0.65 to -0.3), and the overall measure of anxiety and depression (z score: ß = -0.12; 95% CI, -0.17 to -0.08), but there was no association between dog attachment and phobic anxiety (CCI: ß = -0.08; 95% CI, -0.24 to 0.09). All effect sizes for associations were higher when analyses were restricted to women with a history of childhood abuse. Conclusions and relevance: In this explorative cross-sectional study, strong attachment to pets, especially dogs, was associated with lower anxiety and depression symptoms. The favorable association was particularly apparent in women with a history of childhood abuse.

Optimizing the Implementation of a Lifestyle Dementia Prevention Intervention for Older Patients in an Academic Healthcare System.

Background: Interventions that promote healthy lifestyles are critical for the prevention of Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). However, knowledge of the best practices for implementing AD/ADRD prevention in healthcare settings remains limited. Objective: We aimed to qualitatively identify barriers and facilitators to implementing a clinical trial of a novel lifestyle intervention (My Healthy Brain) in our medical center for older patients with subjective cognitive decline who are at-risk for AD/ADRD. Methods: We conducted focus groups with 26 healthcare professionals (e.g., physicians, psychology, nursing) from 5 clinics that treat older patients (e.g., memory care, psychiatry). Our qualitative analysis integrated two implementation frameworks to systematically capture barriers and facilitators to AD/ADRD prevention (Consolidated Framework for Implementation Science Research) that impact implementation outcomes of acceptability, appropriateness, and feasibility (Proctor's framework). Results: We found widespread support for an RCT of My Healthy Brain and AD/ADRD prevention. Participants identified barriers related to patients (stigma, technological skills), providers (dismissiveness of "worried well," doubting capacity for behavior change), clinics (limited time and resources), and the larger healthcare system (underemphasis on prevention). Implementation strategies guided by Expert Recommendations for Implementing Change (ERIC) included: developing tailored materials, training staff, obtaining buy-in from leadership, addressing stigmatized language and practices, identifying "champions," and integrating with workflows and resources. Conclusions: The results will inform our recruitment, enrollment, and retention procedures to implement the first randomized clinical trial of My Healthy Brain. Our study provides a blueprint for addressing multi-level barriers to the implementation of AD/ADRD prevention for older patients in medical settings.

Gratitude and Mortality Among Older US Female Nurses.

Importance: Supporting healthy aging is a US public health priority, and gratitude is a potentially modifiable psychological factor that may enhance health and well-being in older adults. However, the association between gratitude and mortality has not been studied. Objective: To examine the association of gratitude with all-cause and cause-specific mortality in later life. Design, Setting, and Participants: This population-based prospective cohort study used data from self-reported questionnaires and medical records of 49 275 US older female registered nurses who participated in the Nurses' Health Study (2016 questionnaire wave to December 2019). Cox proportional hazards regression models estimated the hazard ratio (HR) of deaths by self-reported levels of gratitude at baseline. These models adjusted for baseline sociodemographic characteristics, social participation, physical health, lifestyle factors, cognitive function, and mental health. Data analysis was conducted from December 2022 to April 2024. Exposure: Gratitude was assessed with the 6-item Gratitude Questionnaire, a validated and widely used measure of one's tendency to experience grateful affect. Main Outcomes and Measures: Deaths were identified from the National Death Index, state statistics records, reports by next of kin, and the postal system. Causes of death were ascertained by physicians through reviewing death certificates and medical records. Results: Among the 49 275 participants (all female; mean [SD] age at baseline, 79 [6.16] years), 4608 incident deaths were identified over 151 496 person-years of follow-up. Greater gratitude at baseline was associated with a lower hazard of mortality in a monotonic fashion. For instance, the highest tertile of gratitude, compared with the lowest tertile, was associated with a lower hazard of all-cause deaths (HR, 0.91; 95% CI, 0.84-0.99) after adjusting for baseline sociodemographic characteristics, social participation, religious involvement, physical health, lifestyle factors, cognitive function, and mental health. When considering cause-specific deaths, death from cardiovascular disease was inversely associated with gratitude (HR, 0.85; 95% CI, 0.73-0.995). Conclusions and Relevance: This study provides the first empirical evidence suggesting that experiencing grateful affect is associated with increased longevity among older adults. The findings will need to be replicated in future studies with more representative samples.

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.

From Diversity, Equity, and Inclusion to an Antiracism Strategic Plan: An Academic Department of Psychiatry's Journey.

The efforts of an academic psychiatry department to embark on an antiracism strategic planning process are outlined, including the establishment of an antiracism task force charged with the development of an antiracism strategic plan. The initial process of the task force is described, recommendations are summarized, and future directions are outlined.

Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS.

BACKGROUND: Longer effects of multivitamin-mineral (MVM) supplementation on late-life cognitive function remain untested using in-person, detailed neuropsychological assessments. Furthermore, insufficient evidence exists for healthcare providers to recommend daily MVM supplements to prevent cognitive decline. OBJECTIVES: This study aimed to test MVM effects on cognitive change using in-person, detailed neuropsychological assessments and conduct a meta-analysis within COSMOS (COcoa Supplement and Multivitamin Outcomes Study) cognitive substudies for a robust evaluation of MVM effects on cognition. METHODS: COSMOS is a 2 × 2 factorial trial of cocoa extract (500 mg flavanols/d) and/or a daily MVM supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests administered at baseline. For the meta-analysis, we included nonoverlapping participants across 3 COSMOS cognitive substudies: COSMOS-Clinic (n = 573); COSMOS-Mind (n = 2158); COSMOS-Web (n = 2472). RESULTS: In COSMOS-Clinic, we observed a modest benefit of MVM compared with placebo on global cognition over 2 y {mean difference [95% confidence interval (CI)] = 0.06 SD units (SU) (-0.003, 0.13)}, with a significantly more favorable change in episodic memory [mean difference (95% CI) = 0.12 SU (0.002, 0.23)] but not in executive function or attention [mean difference (95% CI) = 0.04 SU (-0.04, 0.11)]. The meta-analysis of COSMOS substudies showed clear evidence of MVM benefits on global cognition [mean difference (95% CI) = 0.07 SU (0.03, 0.11); P = 0.0009] and episodic memory [mean difference (95% CI) = 0.06 SU (0.03, 0.10); P = 0.0007]; the magnitude of effect on global cognition was equivalent to reducing cognitive aging by 2 y. CONCLUSIONS: In COSMOS-Clinic, daily MVM supplementation leads to a significantly more favorable 2-y change in episodic memory. The meta-analysis within COSMOS cognitive substudies indicates that daily MVM significantly benefits both global cognition and episodic memory. These findings within the COSMOS trial support the benefits of a daily MVM in preventing cognitive decline among older adults. This trial was registered at COSMOS-clinicaltrials.gov as NCT02422745, at COSMOS-Mind-clinicaltrials.gov as NCT03035201, and at COSMOS-Web-clinicaltrials.gov as NCT04582617.

Timing and duration of dog walking and dog owner's chronotype in relation to incident depression risk among middle to older-aged female nurses.

BACKGROUND: We examined associations between dog ownership, morning dog walking and its timing and duration, and depression risk in female nurses, exploring effect modification by chronotype. We hypothesized that dog ownership and morning walking with the dog are associated with lower odds of depression, and that the latter is particularly beneficial for evening chronotypes by helping them to synchronize their biological clock with the solar system. METHODS: 26,169 depression-free US women aged 53-72 from the Nurses' Health Study 2 (NHS2) were prospectively followed from 2017-2019. We used age- and multivariable-adjusted logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for depression according to dog ownership, and morning dog walking, duration, and timing. RESULTS: Overall, there was no association between owning a dog (ORvs_no_pets = 1.12, 95%CI = 0.91-1.37), morning dog walking (ORvs_not = 0.87, 95%CI = 0.64-1.18), or the duration (OR>30min vs. ≤15mins = 0.68, 95%CI = 0.35-1.29) or timing of morning dog walks (ORafter9am vs. before7am = 1.06, 95%CI = 0.54-2.05) and depression. Chronotype of dog owners appeared to modify these associations. Compared to women of the same chronotype but without pets, dog owners with evening chronotypes had a significantly increased odds of depression (OR = 1.60, 95%CI = 1.12-2.29), whereas morning chronotypes did not (OR = 0.94, 95%CI = 0.71-1.23). Further, our data suggested that evening chronotypes benefited more from walking their dog themselves in the morning (OR = 0.75, 95%CI = 0.46-1.23, Pintx = 0.064;) than morning chronotypes. CONCLUSIONS: Overall, dog ownership was not associated with depression risk though it was increased among evening chronotypes. Walking their dog in the morning might help evening chronotypes to lower their odds of depression, though more data are needed to confirm this finding.

Apolipoprotein E and Its Association With Cognitive Change and Modification of Treatment Effects of Vitamin D3 and Omega-3s on Cognitive Change: Results From the In-Clinic Subset of a Randomized Clinical Trial.

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; and (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 2 × 2 factorial trial testing vitamin D3 (2 000 IU per day), omega-3s (1 g per day), 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 noncarriers, 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. CONCLUSIONS: 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.

Effect of cocoa extract supplementation on cognitive function: results from the clinic subcohort of the COSMOS trial.

BACKGROUND: Some prior randomized clinical trials (RCTs) that tested the effects of cocoa extract (CE), a source of flavanols, on late-life cognition have yielded promising findings. A long-term RCT using in-person neuropsychological tests covering multiple cognitive domains may clarify the cognitive effects of CE. OBJECTIVES: To test whether daily supplementation with CE, compared with placebo, produces better cognitive change over 2 y. METHODS: The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a 2 × 2 factorial RCT of CE [500 mg flavanols/d, including 80 mg (-)-epicatechin] and/or a daily multivitamin-mineral supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests at baseline; of these, 492 completed 2-y follow-up assessments. The primary outcome was global cognition (averaging z-scores across 11 tests). Secondary outcomes were episodic memory and executive function/attention. Repeated measures models were used to compare randomized groups. RESULTS: Participants' mean age (standard deviation) was 69.6 (5.3); 49.2% were females. Daily supplementation with CE, compared with placebo, had no significant effect on 2-y change in global cognition {mean difference [95% confidence interval (CI)]: -0.01 (-0.08, 0.05) standard deviation units (SU)}. CE, compared with placebo, had no significant effects on 2-y change in episodic memory [mean difference (95% CI): -0.01 (-0.13, 0.10) SU] or executive function/attention [mean difference (95% CI): 0.003 (-0.07, 0.08) SU]. Subgroup analyses uncorrected for multiple-testing suggested cognitive benefits of CE supplementation, compared with placebo among those with poorer baseline diet quality. CONCLUSIONS: Among 573 older adults who underwent repeat in-person, detailed neuropsychological assessments over 2 y, daily CE supplementation, compared with placebo, showed no overall benefits for global or domain-specific cognitive function. Possible cognitive benefits of CE among those with poorer diet quality warrant further study. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov with identifier - NCT02422745.

Consumption of Ultraprocessed Food and Risk of Depression.

This cohort study examines the consumption of ultraprocessed food and risk of depression among 31 172 US females aged 42 to 62 years.

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.

Advanced Research Institute (ARI): Supporting the Geriatric Mental Health Research Pipeline.

The Advanced Research Institute (ARI) in Mental Health and Aging is a NIMH-funded mentoring network to help transition early-career faculty to independent investigators and scientific leaders. Since 2004, ARI has enrolled 184 Scholars from 61 institutions across 34 states. We describe the ARI components and assess the impact and outcomes of ARI on research careers of participants. Outcomes of ARI graduates (n = 165) came from NIH Reporter, brief surveys, and CVs: 87.3% remained active researchers, 83.6% performed scientific service, and 80.6% obtained federal grants. A population-based analysis examined NIMH mentored K awardees initially funded from 2002-2018 (n = 1160): in this group, 77.1% (47/61) of ARI participants versus 49.5% (544/1099) of nonparticipants obtained an R01. Controlling for time, ARI participants were 3.2 times more likely to achieve R01 funding than nonparticipants. Given the struggle to reduce attrition from the research career pipeline, the effectiveness of ARI model could be relevant to other fields.

Individuals with depression exhibiting a pro-inflammatory phenotype receiving omega-3 polyunsaturated fatty acids experience improved motivation-related cognitive function: Preliminary results from a randomized controlled trial.

Cognitive impairment related to major depressive disorder (MDD) is highly prevalent, debilitating and is lacking in effective treatments; dysregulated inflammatory physiology is a putative mechanism and may represent a therapeutic target. In depressed individuals exhibiting a pro-inflammatory phenotype who were enrolled in a 12-week randomized placebo-controlled trial of 3 doses of omega-3 polyunsaturated fatty acids (ω-3-FA), we examined: (i) the relationship between dysregulated inflammatory physiology and baseline cognitive impairment; (ii) improvement in cognitive impairment following treatment; and (iii) the association between baseline inflammatory biomarkers and change in cognitive impairment for those receiving treatment. We randomized 61 unmedicated adults aged 45.50 years (75% female) with DSM-5 MDD, body mass index >25 kg/m2, and C-reactive protein (CRP) ≥3.0 mg/L to three doses of ω-3-FA (1, 2, or 4 g daily) or matching placebo. Analyses focused on 45 study completers who had inflammatory biomarkers assessed [circulating CRP, interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) as well as lipopolysaccharide (LPS)-stimulated concentrations of IL-6 and TNFα in peripheral blood mononuclear cells (PBMC)] and on the highest dose ω-3-FA (4 g daily; n = 11) compared to placebo (n = 10). Impairment in motivational symptoms (e.g., alertness, energy, enthusiasm) and higher-order cognitive functions (e.g., word-finding, memory) were assessed by a validated self-report measure. Among all 45 participants at baseline, lower concentrations of IL-6 in LPS-stimulated PBMC were associated with greater impairment in higher-order cognitive functions (r = -0.35, p = .02). Based on hierarchical linear modeling, individuals receiving 4 g/day of ω-3-FA reported significant improvement in motivational symptoms compared to placebo (B = -0.07, p = .03); in the 4 g/day group, lower baseline concentrations of TNFα in LPS-stimulated PBMC were associated with significant improvement in motivational symptoms (Ρ = .71, p = .02) following treatment. In this exploratory clinical trial, daily supplementation with 4 g of ω-3-FA improves motivational symptoms in depressed individuals exhibiting an inflammatory phenotype.

Metabolomics and Self-Reported Depression, Anxiety, and Phobic Symptoms in the VA Normative Aging Study.

Traditional approaches to understanding metabolomics in mental illness have focused on investigating a single disorder or comparisons between diagnoses, but a growing body of evidence suggests substantial mechanistic overlap in mental disorders that could be reflected by the metabolome. In this study, we investigated associations between global plasma metabolites and abnormal scores on the depression, anxiety, and phobic anxiety subscales of the Brief Symptom Inventory (BSI) among 405 older males who participated in the Normative Aging Study (NAS). Our analysis revealed overlapping and distinct metabolites associated with each mental health dimension subscale and four metabolites belonging to xenobiotic, carbohydrate, and amino acid classes that were consistently associated across all three symptom dimension subscales. Furthermore, three of these four metabolites demonstrated a higher degree of alteration in men who reported poor scores in all three dimensions compared to men with poor scores in only one, suggesting the potential for shared underlying biology but a differing degree of perturbation when depression and anxiety symptoms co-occur. Our findings implicate pathways of interest relevant to the overlap of mental health conditions in aging veterans and could represent clinically translatable targets underlying poor mental health in this high-risk population.

Effects of Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation on Indicated and Selective Prevention of Depression in Older Adults: Results From the Clinical Center Sub-Cohort of the VITamin D and OmegA-3 TriaL (VITAL).

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.

Relation of serum BDNF to major depression and exploration of mechanistic roles of serum BDNF in a study of vitamin D3 and omega-3 supplements for late-life depression prevention.

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.

Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults.

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.

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.