Neurobiological correlates of religious coping among older adults with and without mood disorders: An exploratory study.

In this study, 32 older adults with and without mood disorders completed resting-state functional Magnetic Resonance Imaging and measures of demographics, spirituality/religion, positive and negative religious coping, and depression. Group Independent Component Analysis identified and selected three a priori resting state networks [cingulo-opercular salience (cSN), central executive (CEN) and Default Mode Networks (DMN)] within the Triple Network Mode. We investigated associations of religious coping with within- and between-network connectivity, controlling for age. Insular connectivity within the cSN was associated with negative religious coping. Religious coping was associated with anti-correlation between the DMN and CEN even when controlling for depression.

Bipolar symptoms, somatic burden and functioning in older-age bipolar disorder: A replication study from the global aging & geriatric experiments in bipolar disorder database (GAGE-BD) project.

OBJECTIVES: The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232, mean ± standard deviation age 47.2 ± 13.5, 65% women, 49% aged over 50) dataset. DESIGN/METHODS: Using mixed models with random effects for cohort, we examined associations between BD symptoms, somatic burden and age and the contribution of these to functioning in W2 and the combined W1 + W2 sample (n = 2601). RESULTS: Compared to W1, the W2 sample was younger (p < 0.001), less educated (p < 0.001), more symptomatic (p < 0.001), lower functioning (p < 0.001) and had fewer somatic conditions (p < 0.001). In the full W2, older individuals had reduced manic symptom severity, but age was not associated with depression severity. Age was not associated with functioning in W2. More severe BD symptoms (mania p ≤ 0.001, depression p ≤ 0.001) were associated with worse functioning. Older age was significantly associated with higher somatic burden in the W2 and the W1 + W2 samples, but this burden was not associated with poorer functioning. CONCLUSIONS: In a large, independent sample, older age was associated with less severe mania and more somatic burden (consistent with previous findings), but there was no association of depression with age (different from previous findings). Similar to previous findings, worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning.

Neuropsychological Assessments of Cognitive Impairment in Major Depressive Disorder: A Systematic Review and Meta-Analysis with Meta-Regression.

INTRODUCTION: Cognitive dysfunction or deficits are common in patients with major depressive disorder (MDD). The current study systematically reviews and meta-analyzes multiple domains of cognitive impairment in patients with MDD. METHODS: PubMed/MEDLINE, PsycINFO, Cochrane Library, Embase, Web of Science, and Google Scholar were searched from inception through May 17, 2023, with no language limits. Studies with the following inclusion criteria were included: (1) patients with a diagnosis of MDD using standardized diagnostic criteria; (2) healthy controls (i.e., those without MDD); (3) neuropsychological assessments of cognitive impairment using Cambridge Neuropsychological Test Automated Battery (CANTAB); and (4) reports of sufficient data to quantify standardized effect sizes. Hedges' g standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were used to quantify effect sizes of cognitive impairments in MDD. SMDs were estimated using a fixed- or random-effects models. RESULTS: Overall, 33 studies consisting of 2,596 subjects (n = 1,337 for patients with MDD and n = 1,259 for healthy controls) were included. Patients with MDD, when compared to healthy controls, had moderate cognitive deficits (SMD, -0.39 [95% CI, -0.47 to -0.31]). In our subgroup analyses, patients with treatment-resistant depression (SMD, -0.56 [95% CI, -0.78 to -0.34]) and older adults with MDD (SMD, -0.51 [95% CI, -0.66 to -0.36]) had greater cognitive deficits than healthy controls. The effect size was small among unmedicated patients with MDD (SMD, -0.19 [95% CI, -0.37 to -0.00]), and we did not find any statistical difference among children. Cognitive deficits were consistently found in all domains, except the reaction time. No publication bias was reported. CONCLUSION: Because cognitive impairment in MDD can persist in remission or increase the risk of major neurodegenerative disorders, remediation of cognitive impairment in addition to alleviation of depressive symptoms should be an important goal when treating patients with MDD.

A Novel Approach to Monitoring Cognitive Adverse Events for Interventional Studies Involving Advanced Dementia Patients: Insights From the Electroconvulsive Therapy for Agitation in Dementia Study.

OBJECTIVE: To develop an individualized method for detecting cognitive adverse events (CAEs) in the context of an ongoing trial of electroconvulsive therapy for refractory agitation and aggression for advanced dementia (ECT-AD study). METHODS: Literature search aimed at identifying (a) cognitive measures appropriate for patients with advanced dementia, (b) functional scales to use as a proxy for cognitive status in patients with floor effects on baseline cognitive testing, and (c) statistical approaches for defining a CAE, to develop CAEs monitoring plan specifically for the ECT-AD study. RESULTS: Using the Severe Impairment Battery-8 (SIB-8), baseline floor effects are defined as a score of ≤5/16. For patients without floor effects, a decline of ≥6 points is considered a CAE. For patients with floor effects, a decline of ≥30 points from baseline on the Barthel Index is considered a CAE. These values were derived using the standard deviation index (SDI) approach to measuring reliable change. CONCLUSIONS: The proposed plan accounts for practical and statistical challenges in detecting CAEs in patients with advanced dementia. While this protocol was developed in the context of the ECT-AD study, the general approach can potentially be applied to other interventional neuropsychiatric studies that carry the risk of CAEs in patients with advanced dementia.

Sex Differences Among Older Adults With Bipolar Disorder: Results From the Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) Project.

OBJECTIVE: Sex-specific research in adult bipolar disorder (BD) is sparse and even more so among those with older age bipolar disorder (OABD). Knowledge about sex differences across the bipolar lifespan is urgently needed to target and improve treatment. To address this gap, the current study examined sex differences in the domains of clinical presentation, general functioning, and mood symptoms among individuals with OABD. METHODS: This Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) study used data from 19 international studies including BD patients aged ≥50 years (N = 1,185: 645 women, 540 men).A comparison of mood symptoms between women and men was conducted initially using two-tailed t tests and then accounting for systematic differences between the contributing cohorts by performing generalized linear mixed models (GLMMs). Associations between sex and other clinical characteristics were examined using GLMM including: age, BD subtype, rapid cycling, psychiatric hospitalization, lifetime psychiatric comorbidity, and physical health comorbidity, with study cohort as a random intercept. RESULTS: Regarding depressive mood symptoms, women had higher scores on anxiety and hypochondriasis items. Female sex was associated with more psychiatric hospitalizations and male sex with lifetime substance abuse disorders. CONCLUSION: Our findings show important clinical sex differences and provide support that older age women experience a more severe course of BD, with higher rates of psychiatric hospitalization. The reasons for this may be biological, psychological, or social. These differences as well as underlying mechanisms should be a focus for healthcare professionals and need to be studied further.

Efficacy and safety of ketamine-assisted electroconvulsive therapy in major depressive episode: a systematic review and network meta-analysis.

OBJECTIVE: To meta-analyze clinical efficacy and safety of ketamine compared with other anesthetic agents in the course of electroconvulsive therapy (ECT) in major depressive episode (MDE). METHODS: PubMed/MEDLINE, Cochrane Library, Embase, GoogleScholar, and US and European trial registries were searched from inception through May 23, 2023, with no language limits. We included RCTs with (1) a diagnosis of MDE; (2) ECT intervention with ketamine and/or other anesthetic agents; and (3) measures included: depressive symptoms, cognitive performance, remission or response rates, and serious adverse events. Network meta-analysis (NMA) was performed to compare ketamine and 7 other anesthetic agents. Hedges' g standardized mean differences (SMDs) were used for continuous measures, and relative risks (RRs) were used for other binary outcomes using random-effects models. RESULTS: Twenty-two studies were included in the systematic review. A total of 2322 patients from 17 RCTs were included in the NMA. The overall pooled SMD of ketamine, as compared with propofol as a reference group, was -2.21 (95% confidence interval [CI], -3.79 to -0.64) in depressive symptoms, indicating that ketamine had better antidepressant efficacy than propofol. In a sensitivity analysis, however, ketamine-treated patients had a worse outcome in cognitive performance than propofol-treated patients (SMD, -0.18; 95% CI, -0.28 to -0.09). No other statistically significant differences were found. CONCLUSIONS: Ketamine-assisted ECT is tolerable and may be efficacious in improving depressive symptoms, but a relative adverse impact on cognition may be an important clinical consideration. Anesthetic agents should be considered based on patient profiles and/or preferences to improve effectiveness and safety of ECT use.

Demographic and clinical associations to employment status in older-age bipolar disorder: Analysis from the GAGE-BD database project.

OBJECTIVE: The current literature on employment in older adults with bipolar disorder (OABD) is limited. Using the Global Aging and Geriatric Experiments in Bipolar Disorder Database (GAGE-BD), we examined the relationship of occupational status in OABD to other demographic and clinical characteristics. METHODS: Seven hundred and thirty-eight participants from 11 international samples with data on educational level and occupational status were included. Employment status was dichotomized as employed versus unemployed. Generalized linear mixed models with random intercepts for the study cohort were used to examine the relationship between baseline characteristics and employment. Predictors in the models included baseline demographics, education, psychiatric symptom severity, psychiatric comorbidity, somatic comorbidity, and prior psychiatric hospitalizations. RESULTS: In the sample, 23.6% (n = 174) were employed, while 76.4% were unemployed (n = 564). In multivariable logistic regression models, less education, older age, a history of both anxiety and substance/alcohol use disorders, more prior psychiatric hospitalizations, and higher levels of BD depression severity were associated with greater odds of unemployment. In the subsample of individuals less than 65 years of age, findings were similar. No significant association between manic symptoms, gender, age of onset, or employment status was observed. CONCLUSION: Results suggest an association between educational level, age, psychiatric severity and comorbidity in relation to employment in OABD. Implications include the need for management of psychiatric symptoms and comorbidity across the lifespan, as well as improving educational access for people with BD and skills training or other support for those with work-life breaks to re-enter employment and optimize the overall outcome.

Effects of lithium on serum Brain-Derived Neurotrophic Factor in Alzheimer's patients with agitation.

BACKGROUND: There is ample evidence in animal models that lithium increases Brain-Derived Neurotrophic Factor (BDNF) with supporting evidence in human studies. Little is known, however, about the effects of lithium on BDNF in Alzheimer's Dementia (AD). In one study of patients with Mild Cognitive Impairment, serum BDNF increased after treatment with lithium. These patients also showed mild improvement in cognitive function. OBJECTIVES: To evaluate low-dose lithium treatment of agitation in Alzheimer's disease (AD). METHOD: We measured levels of BDNF in patients treated with lithium prior to and after a 12-week randomized placebo-controlled trial. RESULTS: BDNF levels did not change significantly and were not associated with improvement in overall neuropsychiatric symptoms or in cognitive function. CONCLUSIONS: More research is needed to understand the potential effects of lithium on BDNF in AD including whether its use might be dependent on the stage of cognitive decline and dementia.

The needs of family caregivers of persons living with dementia cared for in primary care practices.

RATIONALE: The informal caregivers who provide unpaid support for persons living with dementia (PLWD) are often unprepared to appropriately manage symptoms and navigate health services to support themselves or the PLWD. AIM: To understand informal caregivers' perceived capabilities of handling dementia symptomology and perceived support from providers. METHODS: We identified and surveyed caregivers of primary care patients in the Mass General Brigham health system. We included a self-efficacy questionnaire to assess caregivers' ability and confidence in access to dementia care, symptom management, and provider support. RESULTS: Respondents indicated that although their provider had knowledge of dementia and memory care, they were least likely to agree (39.2%) that their provider helped them with these challenging symptoms. Those who live with the care recipient were least likely to receive advice about common symptoms (43.6%) and to access community services (63.8%), and in general felt moderately knowledgeable about the progression of the disease (47.9%). CONCLUSIONS: The findings imply that caregivers are aware of disease progression, dementia symptoms, and do not feel supported by their providers in managing care or accessing support services. There is opportunity to support informal caregivers in a primary care setting by appropriately uptraining providers in dementia care.

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.

Essential data dimensions for prospective international data collection in older age bipolar disorder (OABD): Recommendations from the GAGE-BD group.

BACKGROUND: By 2030, over 50% of individuals living with bipolar disorder (BD) are expected to be aged ≥50 years. However, older age bipolar disorder (OABD) remains understudied. There are limited large-scale prospectively collected data organized in key dimensions capable of addressing several fundamental questions about BD affecting this subgroup of patients. METHODS: We developed initial recommendations for the essential dimensions for OABD data collection, based on (1) a systematic review of measures used in OABD studies, (2) a Delphi consensus of international OABD experts, (3) experience with harmonizing OABD data in the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD, n ≥ 4500 participants), and (4) critical feedback from 34 global experts in geriatric mental health. RESULTS: We identified 15 key dimensions and variables within each that are relevant for the investigation of OABD: (1) demographics, (2) core symptoms of depression and (3) mania, (4) cognition screening and subjective cognitive function, (5) elements for BD diagnosis, (6) descriptors of course of illness, (7) treatment, (8) suicidality, (9) current medication, (10) psychiatric comorbidity, (11) psychotic symptoms, (12) general medical comorbidities, (13) functioning, (14) family history, and (15) other. We also recommend particular instruments for capturing some of the dimensions and variables. CONCLUSION: The essential data dimensions we present should be of use to guide future international data collection in OABD and clinical practice. In the longer term, we aim to establish a prospective consortium using this core set of dimensions and associated variables to answer research questions relevant to OABD.

Does use of primary care-based behavioral health programs differ by race and ethnicity? Evidence from a multi-site collaborative care model.

BACKGROUND: Collaborative care models (CoCM) that integrate mental health and primary care improve outcomes and could help address racial and ethnic mental health disparities. We examined whether use of these programs differs by race/ethnicity. METHODS: This retrospective study examined two CoCM interventions implemented across primary care clinics in a large health system in Massachusetts: 1) a primary care-based behavioral health program for depression or anxiety (IMPACT model) and 2) referral to community-based specialty care services (Resource-finding). Outcomes included enrollment, non-completion, and symptom screening rates, and discharge status for Black, Hispanic and White patients referred for CoCM, 2017-2019. RESULTS: Black and Hispanic vs. White patients referred to CoCM (n = 17,280) were more likely to live in high poverty ZIP codes (34% and 40% vs. 9%). Rates of program enrollment, non-completion, and symptom screening were similar across groups (e.g., 76%, 77%, and 75% of Black, Hispanic, and White patients enrolled). Hispanic vs. White patients were more likely to be enrolled in IMPACT (56%) vs. Resource-finding (43%). Among those completing IMPACT, Hispanic vs. White patients were more likely to be stepped to psychiatry vs. discharged to their primary care provider (51% vs. 20%, aOR = 1.55, 95% CI: 1.02-2.35). CONCLUSIONS: Black and Hispanic patients referred to CoCM were similarly likely to use the program as White patients. Hispanic patients completing IMPACT were more frequently referred to psychiatry. IMPLICATIONS: These results highlight the promise of CoCMs for engaging minority populations in mental healthcare. Hispanic patients may benefit from additional intervention or earlier linkage to specialty care.

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.

Impact of dementia care training on nurse care managers' interactions with family caregivers.

BACKGROUND: Nurse care managers (NCM) operate through care management programs to provide care for persons living with dementia (PLWD) and interact regularly with their family caregivers; however, most do not receive formal instruction in dementia care or caregiver support. CRESCENT (CaReEcoSystem primary Care Embedded demeNtia Treatment) is a telephone-based dementia care intervention adapted from the Care EcoSystem model designed to equip NCMs with these tools. For this study, we aimed to measure intervention fidelity and understand how dementia care training impacted NCMs' provision of dementia care management services during interactions with caregivers of PLWD. METHODS: We recruited 30 active NCMs; 15 were randomly assigned to receive training. For each nurse, we randomly selected 1-3 patients with a diagnosis of dementia in each nurse's care during January-June 2021 for a total of 54 medical charts. To assess training uptake and fidelity, we identified documentation by NCMs of CRESCENT protocol implementation in the medical records. To understand how the training impacted the amount and types of dementia care management services provided in interactions with family caregivers, we compared attention to key dementia topic areas between trained NCMs (intervention) and untrained NCMs (control). RESULTS: Within the trained group only, community resources for PLWD, followed by safety, medication reconciliation, and advanced care planning topic areas were addressed most frequently (> 30%), while behavior management was addressed least frequently (12%). Trained NCMs were more likely to document addressing aspects of caregiver wellbeing (p = 0.03), community resources (p = 0.002), and identification of behavior (p = 0.03) and safety issues (p = 0.02) compared to those without training. There was no difference between groups in the amount of care coordination provided (p = 0.64). CONCLUSION: Results from this study demonstrate that focused dementia care training enriches care conversations in important topic areas for PLWD and family caregivers. Future research will clarify how best to sustain and optimize high quality dementia care in care management programs with special attention to the NCM-family caregiver relationship. TRIAL NUMBER: NCT04556097.

Effects of Electroconvulsive Therapy on Functional Outcomes Among Medicare Patients With Comorbid Depression and Dementia: A Nationwide 1-Year Follow-Up Study.

Objective: Current treatments for behavioral and psychological symptoms of dementia (BPSD) are of limited efficacy. Electroconvulsive therapy (ECT) is an effective and safe treatment for a range of psychiatric disorders, with some limited data suggesting a role in treating BPSD. We sought to expand this growing literature by examining-in a rigorous way with a larger sample size than in previous reports-the potential of ECT as a treatment for comorbid depression and dementia.Methods: Drawing on nationally representative 2014-2015 Medicare claims data, propensity score methods were used to create two comparable cohorts consisting of ECT-treated patients (n = 147) and controls (n = 415) who were hospitalized with a principal psychiatric diagnosis. Functional outcomes were compared before and after hospitalization (when ECT was initiated for the ECT cohort).Results: Both cohorts generally declined in all functional outcomes over the time period observed. The ECT cohort had a slower rate of functional decline in bathing (Cohen d = -0.05 vs 0.38; P < .001) and transferring (d = 0.18 vs 0.45; P = .031) compared to matched controls. In multivariate analysis, ECT patients also fared better in the overall activities of daily living summary score at 180 days (coefficient = -0.10; 95% CI, -0.19 to 0.01), though these effects were small. No difference was seen in cognition or ambulation.Discussion: Receiving ECT does not worsen the trajectory of functional outcomes compared to not receiving ECT in older adults with comorbid depression. Randomized clinical trials are needed to more definitively examine the causal effect of ECT on functional outcomes of individuals with dementia.

Bipolar I and bipolar II subtypes in older age: Results from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) project.

OBJECTIVES: The distinction between bipolar I disorder (BD-I) and bipolar II disorder (BD-II) has been a topic of long-lasting debate. This study examined differences between BD-I and BD-II in a large, global sample of OABD, focusing on general functioning, cognition and somatic burden as these domains are often affected in OABD. METHODS: Cross-sectional analyses were conducted with data from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) database. The sample included 963 participants aged ≥50 years (714 BD-I, 249 BD-II). Sociodemographic and clinical factors were compared between BD subtypes including adjustment for study cohort. Multivariable analyses were conducted with generalized linear mixed models (GLMMs) and estimated associations between BD subtype and (1) general functioning (GAF), (2) cognitive performance (g-score) and (3) somatic burden, with study cohort as random intercept. RESULTS: After adjustment for study cohort, BD-II patients more often had a late onset ≥50 years (p = 0.008) and more current severe depression (p = 0.041). BD-I patients were more likely to have a history of psychiatric hospitalization (p < 0.001) and current use of anti-psychotics (p = 0.003). Multivariable analyses showed that BD subtype was not related to GAF, cognitive g-score or somatic burden. CONCLUSION: BD-I and BD-II patients did not differ in terms of general functioning, cognitive impairment or somatic burden. Some clinical differences were observed between the groups, which could be the consequence of diagnostic definitions. The distinction between BD-I and BD-II is not the best way to subtype OABD patients. Future research should investigate other disease specifiers in this population.

Effects of religion on the course of suicidality among geriatric patients with mood disorders.

BACKGROUND: A growing volume of research suggests that religion protects against late-life suicide, but it remains unclear whether effects are relevant to clinical samples, which facets of religion are most relevant, and variations over the course of mood disorders (e.g. during periods of euthymia, depression, and/or heightened suicidality). METHOD: Eighty adults aged 55-85 years with mood disorders completed assessments of religion (affiliation, service attendance, importance of religion, belief and faith in God), depression, and suicidality over time (M = 7.31 measurements over M = 727 days). We computed metrics to identify mean and maximum levels of depression and suicidality, and the number of episodes of significant depression and suicidality experienced by each participant. RESULTS: Religious affiliation and importance of religion, but not service attendance, belief, or faith in God, were associated with lower mean and maximum depression. Conversely, all facets of religion predicted significantly lower mean and maximum levels of suicidality (rs ranging from -0.24 to -0.39), and substantially less likelihood of experiencing significant suicidality during the study (ORs ranging from 0.19 to 0.33). Service attendance, belief, and faith in God predicted less suicidality even among individuals who did not affiliate with a religious group. CONCLUSIONS: Religious factors, particularly faith in God, are associated with substantially less suicidality over time among older adults with mood disorders, irrespective of religious affiliation.

Predictors of Functional Impairment in Bipolar Disorder: Results From 13 Cohorts From Seven Countries by the Global Bipolar Cohort Collaborative.

Objectives: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD. Methods: Thirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived "higher versus lower function" as the dependent variable and selected clinical and demographic variables as predictors. Results: We found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning. Conclusions: The bipolar clinical research community is poised to work together to characterize the multi-dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large-scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness.Reprinted from Bipolar Disord 2022; 24:709-719, with permission from John Wiley and Sons. Copyright © 2022.

Clinical correlates of late-onset versus early-onset bipolar disorder in a global sample of older adults.

OBJECTIVES: Late-onset bipolar disorder (LOBD) represents a significant subgroup of bipolar disorder (BD). However, knowledge for this group is mostly extrapolated from small studies in subjects with early/mixed age of illness onset. In this global sample of older adults with BD (OABD: ≥50 years old) we aim to characterize the sociodemographic and clinical presentation of LOBD (≥40 years at BD onset) compared to early-onset BD (EOBD: <40 years at BD onset). METHODS: The Global Aging and Geriatric Experiments in Bipolar Disorder consortium provided international data on 437 older age bipolar disorder participants. We compared LOBD versus EOBD on depression, mania, functionality, and physical comorbidities. Exploratory analyses were performed on participants with BD onset ≥50 years old. RESULTS: LOBD (n = 105) did not differ from EOBD (n = 332) on depression, mania, global functioning, nor employment status (p > 0.05). Late-onset bipolar disorder was associated with higher endocrine comorbidities (odds ratio = 1.48, [95%CI = 1.0,12.1], p = 0.03). This difference did not remain significant when subjects with BD onset ≥50 years old were analyzed. LIMITATIONS: This study is limited by the retrospective nature of the variable age of onset and the differences in evaluation methods across studies (partially overcame by harmonization processes). CONCLUSION: The present analysis is in favor of the hypothesis that LOBD might represent a similar clinical phenotype as classic EOBD with respect to core BD symptomatology, functionality, and comorbid physical conditions. Large-scale global collaboration to improve our understanding of BD across the lifespan is needed.