Lisa T. Eyler

Background and ObjectivesNeighborhood disadvantage is a recognized risk factor for Alzheimer disease and Alzheimer disease–related dementias (AD/ADRD) and is linked to AD/ADRD pathology at autopsy....

Introductions: Lithium remains the first‐line maintenance treatment for bipolar disorder (BD), yet its safety in older‐age BD (OABD) is uncertain due to limited large‐scale data. OABD patients often experience more severe physical comorbidities compared to younger BD patients, but systematic evidence regarding lithium's association with these conditions is lacking. This study examined the association between lithium use and physical comorbidities across age groups using the international Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE‐BD) dataset. Methods: A cross‐sectional analysis was conducted using combined Wave 1 and 2 data from GAGE‐BD project, encompassing 37 studies from 20 sites worldwide. Participants aged ≥ 18 years with BD were classified according to current lithium use. Physical comorbidities were harmonised into eight organ‐system domains. Sociodemographic and clinical variables were compared between individuals receiving lithium treatment and those not prescribed lithium. Generalised linear mixed models adjusted for age, site and lithium × age interaction were applied to evaluate associations with physical comorbidities. Results: Of the 2873 total participants included in the study, 1069 were currently receiving lithium treatment and 1804 were not prescribed lithium. Participants treated with lithium showed a lower overall prevalence of physical comorbidities compared with those not receiving lithium. Regression analyses revealed significant age‐by‐lithium interactions for cardiovascular (χ ² = 9.27, p = 0.002), respiratory (χ ² = 7.56, p = 0.006), genitourinary (χ ² = 8.66, p = 0.003) and endocrine (χ ² = 16.96, p < 0.001) comorbidities. Model‐estimated curve crossings occurred at approximately 43 years (cardiovascular), 32 years (respiratory), 51 years (genitourinary) and 59 years (endocrine), above which predicted prevalence was lower among participants treated with lithium, whereas no differences were observed for gastrointestinal, hepatic, renal or musculoskeletal systems. Conclusions: Lithium use in OABD was associated with a lower burden of specific physical comorbidities, particularly cardiovascular, respiratory and endocrine conditions. Although prescription bias cannot be excluded, the findings challenge the perception that lithium exacerbates physical health risks in older adults. Instead, they support lithium's continued use—with appropriate monitoring—as a safe and effective treatment option for OABD, and highlight the need for prospective studies to further clarify the relationship between lithium exposure and physical health outcomes.

Background: Older adults with bipolar disorder ( BD ) are at high risk for severe mood symptoms, cognitive difficulties, and early mortality; however, underlying brain alterations have received little study. Gray matter decreases in ventral prefrontal cortex ( VPFC ) seen in younger persons with BD , and additionally in dorsal PFC ( DPFC ), are implicated. Here, cortical thickness was examined in an international sample. Methods: Cortical thickness in 34 regions was measured from structural magnetic resonance imaging data using enhancing neuroImaging genetics through meta‐analysis pipelines for individuals with BD ( n = 308) and non‐psychiatric comparison participants ( n = 287), ages 40–70y, from six Global Aging and Geriatric Experiments in BD ( GAGE ‐ BD ) consortium sites. Group differences were assessed for VPFC , DPFC and remaining cortical regions, covarying for scanner, age and sex. Results were considered significant corrected for false discovery fate ( FDR ) at p _FDR < 0.05. Relationships with demographic and clinical factors were explored. Results: Cortical thickness was significantly lower among BD in VPFC and DPFC , and additional distributed regions ( p _FDR < 0.05) and negatively associated with age ( p < 0.05); group and age did not interact significantly. Relationships with BD subtype and medications were observed; lithium was associated with higher frontal pole and anterior cingulate thickness ( p _FDR < 0.05). Conclusions: In this international middle and older aged adult BD sample, lower VPFC cortical thickness was observed, suggesting these deficits persist from younger age. DPFC and additional regions of reduced cortical thickness could contribute to the older adult BD phenotype. Cortical thinning was more pronounced among older individuals regardless of diagnosis. Lithium may lessen cortical thinning.

Neuroimaging studies show that the functional connectivity of the brain changes with age. Resting state functional connectivity (rsFC) in the brain appears to decrease with aging in key networks associated with higher order thinking and effective emotional regulation. Interventions that potentially preserversFC in the brain include 1) physical activity and 2) contemplative practice commonly referred to as mindfulness. The present narrative review aims to summarize the literature concerning the effect of interventions involving exercise, mindful movement, and purely mindfulness-based training on rsFC. Search terms focused on identifying multi-day exercise, mindfulness, or mindful-movement interventions in non-clinical adult populations that included a control group and both pre- and post-assessment of brain rsFC. Thirty studies were reviewed. Assessed methodological factors that potentially impact findings included subject sample size, scan time length, brain regions targeted for analyses, intervention length and intensity, population characteristics, and differences in sleep quantity/quality. Most studies reported changes in rsFC related to interventions with most observed changes found within the default mode, executive control and salience networks of the brain. However, the largest and most methodologically rigorous study found minimal associations between rsFC and either exercise or mindfulness. Given the inconsistent results found in this review, caution is warranted in the interpretation of changes in rsFC attributable to exercise and mindfulness. This review highlights key factors likely to contribute to differences in reported outcomes. Methodological consistency in fMRI acquisition, data preparation, and analytical approaches are crucial to improve reproducibility and allow for comparison and aggregation.

Background: Empathy, compassion, self-compassion, and resilience are essential to medical practice and education. While some evidence shows that these traits may decline during medical school, few studies have examined all these capacities in the same cohorts or trends within an academic year. This study examines first-year longitudinal findings on cohort and within-year changes in these constructs among medical students. Methods: 98 students (58.2% female; M_age = 26.34 (2.86); 37.8% White; MS1 25.5%, MS2 25.5%, MS3 20.4%, MS4 26.5%) from a large US school participated in at least one wave of an online survey distributed 4 times during the 2023–2024 academic year. Validated measures assessed empathy (IRI), compassion (SCBCS), self-compassion (Neff SCS), and resilience (CD-RISC-10). Linear mixed models analyzed between-cohort differences over time with gender and race/ethnicity as covariates. Results: Compared to MS4 students, MS2 and MS3 students had significantly lower cognitive empathy and self-compassion, with marginally lower compassion and higher resilience (p = 0.06). Women reported higher compassion toward others but lower self-compassion and resilience than men. Conclusions: Lower empathy and compassion were observed as early as the second year of medical school, suggesting erosion factors, such as academic pressure and standardized testing, may impact trainees earlier than previously reported.

Background: Empathy, compassion, self-compassion, and resilience are essential to medical practice and education. While some evidence shows that these traits may decline during medical school, few studies have examined all these capacities in the same cohorts or trends within an academic year. This study examines first-year longitudinal findings on cohort and within-year changes in these constructs among medical students. Methods: 98 students (58.2% female; MS1 25.5%, MS2 25.5%, MS3 20.4%, MS4 26.5%) from a large West Coast school participated in at least one wave of an online survey distributed 4 times during the 2023-2024 academic year. Validated measures assessed empathy (IRI), compassion (SCBCS), self-compassion (Neff SCS), and resilience (CD-RISC-10). Linear Mixed Models analyzed between-cohort differences over time with gender and race/ethnicity as covariates. Results: Compared to MS4 students, MS2 and MS3 students had significantly lower cognitive empathy and self-compassion, with marginally lower compassion and higher resilience (p = 0.06). Women reported higher compassion toward others but lower self-compassion and resilience than men. Conclusions: Lower empathy and compassion were observed as early as the second year of medical school, suggesting erosion factors, such as academic pressure and standardized testing, may impact trainees earlier than previously reported.

BACKGROUND Rigorous clinical research on conditions such as older-age bipolar disorder (OABD) patients is imperative to guide prevention and treatment efforts. Large-scale prospective studies are challenging and resource-intensive; combining existing, smaller datasets allows for powerful analyses that are globally representative. The Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) consortium, which integrates and harmonizes archival data from sites across the world, is one such effort. This requires development of approaches to aid in classifying the domains covered by variables contained in contributed datasets and to set the stage for optimal and efficient harmonization of variables across instruments and data structures. OBJECTIVE To develop a domain-specific ontology for systematically classifying variables in older-age bipolar disorder (OABD) research. To design and implement an computational tool (VariCat) to standardize variable categorization and capture metadata crucial for integration and harmonization across heterogeneous datasets. To demonstrate the capability of this framework via a case study in enabling scalable data integration and harmonization of archival clinical datasets across multiple study cohorts and sites. METHODS Based upon our systematic review of measures used in 53 studies of OABD, and upon data dictionaries and numeric data from 19 cohorts comprising over 1400 individuals with and without bipolar disorder (BD), we developed an ontology of data comprising 20 domains, 102 subdomains, and 129 sub-subdomains for classifying OABD-relevant variables. Subsequently, we created a computer-based interactive program, VariCat, implemented in both Python and REDCap, for data analysts to classify each contributed variable according to its domains/subdomains and to input harmonization-relevant characteristics. RESULTS VariCat provides a way to systematically classify and harmonize heterogeneous variables across datasets by generating a structured metadata repository. Across 37 studies, this approach identified domain coverage (e.g., cognitive variables present in 19 studies) and enabled harmonization of 212 variables into an integrated dataset spanning 20 sites. In a single-site application (UCSD Inflammaging dataset), VariCat categorized all variables and revealed domain distributions (e.g., physical health, illness severity, and cognition as the most represented domains). Across datasets, the framework identified commonly used instruments (e.g., Trail Making Test Part B) and enabled systematic identification of data gaps and harmonization opportunities. CONCLUSIONS We developed and employed a bipolar disorder-specific ontology based on existing datasets and literature and incorporated this into a variable categorization program available in two different formats. This work will help better characterize OABD and also benefit the growing number of international consortia that study psychiatric disorders using archival and/or prospective data. CLINICALTRIAL NA

Background and Objectives: There are known associations between bipolar disorder and obesity, but it has not been well characterized in older adults with bipolar disorder (OABD). This study aims to examine body mass index (BMI) and its clinical correlations in OABD. Materials and Methods: A secondary analysis was conducted using data from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) project, an international harmonized dataset of OABD cohorts. To examine the relationship between BMI and clinical characteristics (e.g., sex, psychiatric history, symptom severity, medication use, comorbidities), multivariable linear regression and multinomial logistic regression models with random effect for study cohort were used, with BMI as a continuous and as an ordinal (underweight vs. healthy weight vs. overweight vs. obese) dependent variable, respectively. Results: Of 1,226 OABD participants with BMI data, 405 (33.0%) were classified as overweight (BMI 25–29.99) and 462 (37.7%) as obese (BMI > 30). In linear regression models, higher BMI was associated with younger age, higher number of somatic comorbidities, and anticonvulsant use, while lower BMI was associated with lithium use. In logistic regression models, obesity was associated with cardiovascular comorbidity, musculoskeletal comorbidity and endocrine comorbidity. Conclusions: A high proportion of individuals with OABD are overweight or obese. Several demographic and clinical correlations of higher BMI were found, including younger age, higher number of medical comorbidities and anticonvulsant use. Clinicians should monitor and manage weight changes and associated comorbidities, and promote lifestyle and health interventions to minimize the risk of negative health outcomes associated with high BMI.

The absolute number and relative proportion of individuals with older-age bipolar disorder (OABD) is expected to rise due to the global aging of the population, necessitating a greater understanding of the unique characteristics of OABD and the trajectory of aging with BD in order to improve the health span of people with BD. This review summarizes current knowledge on OABD, examining its clinical presentation, neurobiology, and treatment, as well as identifying key gaps and future directions for research. OABD is characterized by relatively greater cognitive impairment and somatic burden, despite potentially reduced mood symptom severity compared to younger-age bipolar disorder (YABD). This significantly impacts functional outcomes in older age, highlighting the need for age-adjusted clinical strategies. Individual differences in illness course, treatment history, and psychotic features influence the clinical presentation and prognosis in OABD. One powerful strategy to better understand OABD is to bring together existing data from across the globe through large-scale collaborations. In the realm of BD, this is exemplified by several ongoing efforts including the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) initiative and the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder (ENIGMA-BD) working group. Evidence on the trajectory of bipolar disorder (BD) across the lifespan is mixed, with some individuals showing accelerated cognitive and biological aging. Biomarker studies reveal overlaps between YABD and OABD, but also suggest age-specific alterations in inflammation and oxidative stress pathways. Lithium remains a first-line pharmacological treatment in OABD, with emerging evidence supporting other pharmacologic and behavioral interventions, although large-scale, age-specific trials remain limited. Neuromodulation treatment approaches appear promising but remain relatively unexplored in OABD. The review highlights current knowledge gaps, particularly the need for longitudinal research to identify early predictors of impairment, and to guide potential preventative strategies. This summary emphasizes the potential of global consortia and multi-center studies to deepen insights into BD aging trajectories with high generalizability. Ultimately, a lifespan approach that incorporates lived experience, early intervention, and global collaboration is essential to promoting health and well-being in individuals with OABD.