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.

Sociodemographic and clinical characteristics of people with oldest older age bipolar disorder in a global sample: Results from the global aging and geriatric experiments in bipolar disorder project.

OBJECTS: Studies of older age bipolar disorder (OABD) have mostly focused on "younger old" individuals. Little is known about the oldest OABD (OOABD) individuals aged ≥70 years old. The Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) project provides an opportunity to evaluate the OOABD group to understand their characteristics compared to younger groups. METHODS: We conducted cross-sectional analyses of the GAGE-BD database, an integrated, harmonized dataset from 19 international studies. We compared the sociodemographic and clinical characteristics of those aged <50 (YABD, n = 184), 50-69 (OABD, n = 881), and ≥70 (OOABD, n = 304). To standardize the comparisons between age categories and all characteristics, we used multinomial logistic regression models with age category as the dependent variable, with each characteristic as the independent variable, and clustering of standard errors to account for the correlation between observations from each of the studies. RESULTS: OOABD and OABD had lower severity of manic symptoms (Mean YMRS = 3.3, 3.8 respectively) than YABD (YMRS = 7.6), and lower depressive symptoms (% of absent = 65.4%, and 59.5% respectively) than YABD (18.3%). OOABD and OABD had higher physical burden than YABD, especially in the cardiovascular domain (prevalence = 65% in OOABD, 41% in OABD and 17% in YABD); OOABD had the highest prevalence (56%) in the musculoskeletal domain (significantly differed from 39% in OABD and 31% in YABD which didn't differ from each other). Overall, OOABD had significant cumulative physical burden in numbers of domains (mean = 4) compared to both OABD (mean = 2) and YABD (mean = 1). OOABD had the lowest rates of suicidal thoughts (10%), which significantly differed from YABD (26%) though didn't differ from OABD (21%). Functional status was higher in both OOABD (GAF = 63) and OABD (GAF = 64), though only OABD had significantly higher function than YABD (GAF = 59). CONCLUSIONS: OOABD have unique features, suggesting that (1) OOABD individuals may be easier to manage psychiatrically, but require more attention to comorbid physical conditions; (2) OOABD is a survivor cohort associated with resilience despite high medical burden, warranting both qualitative and quantitative methods to better understand how to advance clinical care and ways to age successfully with BD.

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.

Examining the acceptability and feasibility of the Compassionate Mindful Resilience (CMR) programme in adults living with chronic kidney disease: the COSMIC study findings.

BACKGROUND: Individuals with chronic kidney disease experience difficult physical and psychological symptoms, that impact quality of life, and are at increased risk of anxiety and depression. Access to specialist psychological support is limited. This study aimed to support a new service development project, in collaboration with Kidney Care UK, to implement the Compassionate Mindful Resilience (CMR) programme, developed by MindfulnessUK, which provides accessible mindfulness techniques and practices to enhance compassion and resilience, and explore its feasibility for people living with stage 4 or 5 kidney disease and transplant. METHODS: A multi-method feasibility design was utilised. Participants over 18 years, from the UK, with stage 4 or 5 kidney disease or post-transplant, and who were not currently undergoing psychotherapy, were recruited to the four-week CMR programme. Data was collected at baseline, post-intervention and three-months post to measure anxiety, depression, self-compassion, mental wellbeing, resilience, and mindfulness. The acceptability of the intervention for a kidney disease population was explored through qualitative interviews with participants, and the Mindfulness Teacher. RESULTS: In total, 75 participants were recruited to the study, with 65 completing the CMR programme. The majority were female (66.2%) and post-transplant (63.1%). Analysis of completed outcome measures at baseline and post-intervention timepoints (n = 61), and three-months post intervention (n = 45) revealed significant improvements in participant's levels of anxiety (p < .001) and depression (p < .001), self-compassion (p = .005), mental wellbeing (p < .001), resilience (p.001), and mindfulness (p < .001). Thematic analysis of interviews with participants (n = 19) and Mindfulness Teacher (n = 1) generated three themes (and nine-subthemes); experiences of the CMR programme that facilitated subjective benefit, participants lived and shared experiences, and practicalities of programme participation. All participants interviewed reported that they found programme participation to be beneficial. CONCLUSION: The findings suggest that the CMR programme has the potential to improve psychological outcomes among people with chronic kidney disease. Future randomized controlled trials are required to further test its effectiveness.

myHealthHub for older adult inpatients to reduce loneliness, and improve patient engagement and mental health: protocol of a pilot randomized controlled trial.

OBJECTIVES: Older Canadian adults make up 85% of hospital stays which are associated with increased loneliness, stress, anxiety, and/or depression. There is a need for novel approaches to reduce loneliness and mental health outcomes in older adult hospital inpatients to prevent further strain on an already overwhelmed healthcare system. METHODS: This is a pilot randomized controlled trial (RCT) exploring the efficacy of a bedside multimodal interaction system, myHealthHub, on loneliness, quality of life (QOL), patient engagement, and other mental health outcomes compared to an active control group in older adult inpatients (n = 60) from baseline to 5-days. Qualitative analyses will be conducted through semi-structured interviews with older adults (n = 8-10) and hospital staff, nurses, and clinicians (n = 4-5) facilitating the service to evaluate patient engagement and experience with myHealthHub. RESULTS: Not applicable. CONCLUSION: This novel pilot clinical trial will obtain preliminary data on the efficacy of myHealthHub in reducing loneliness, QOL, patient engagement, and mental health outcomes in older adult inpatients. If successful, this could provide a potential means to improve patient experience in hospitals and reduce the burden and additional expense on the healthcare system.

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.

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.

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.

Virtually-Delivered Emotion Focused Mindfulness Therapy (EFMT) Group vs. Wait-List Control for Late-Life Anxiety: A Randomized Controlled Trial.

BACKGROUND: The worldwide annual prevalence of anxiety in older adults is estimated to be between 6% and 10%. Emotion Focused Mindfulness Therapy (EFMT) is a mindfulness-based group intervention that has been demonstrated to reduce symptoms of anxiety in community dwelling adults. No study has yet assessed EFMT for older adults with late-life anxiety. The aim of this study was to determine the feasibility of video-delivered group EFMT for older adults living in community settings, a novel and potentially scalable intervention. METHODS: This was a feasibility randomized controlled trial (RCT) of 48 older adults (≥55 years old), recruited through primary care, community organizations and snowball methods. Participants were randomized to group EFMT delivered by Zoom vs. a wait-list control. Data were collected at baseline (T1), 9 weeks following baseline (T2, primary study endpoint) and 17 weeks following baseline (T3). Random allocation was conducted immediately after each group of 12 participants had been enrolled into the trial, with groups beginning on a rolling basis each time a block of 12 participants had been enrolled. The main efficacy outcome examined changes over time to anxiety. RESULTS: Recruitment was successfully completed in 32 weeks. Enrollment was calculated at 62.3% (48 of 77 people screened). Retention (80.0%) and adherence (100.0% for intervention group participants) were excellent. The EFMT group had significant improvements in anxiety at T2 compared to the wait-list control group (-3.47 [4.12] vs.-1.22 [3.25] points, p = 0.05). CONCLUSIONS: Virtually-delivered EFMT appears to be a feasible, acceptable, and efficacious group treatment to improve late-life anxiety.

Do older adults respond to cognitive behavioral therapy as well as younger adults? An analysis of a large, multi-diagnostic, real-world sample.

OBJECTIVES: Older adults (OA; ≥55 years of age) are underrepresented in patients receiving cognitive-behavioral therapy (CBT). This study evaluates mental health outcomes for OA compared to younger adults (YA; <55 years of age) receiving CBT. DESIGN: This is a pre-post study comparing the effectiveness of CBT for OA (n = 99) and YA (n = 601) in a CBT service located in a university-affiliated tertiary care hospital in Canada. Data was collected between 2001 and 2021. Participants received a mean of 18.5 sessions (SD 10) of standard, evidence-based CBT with treatment integrity checks. The main outcome was clinically significant change, as measured by the Reliable Change Index (RCI). Secondary outcomes were change in the Global Severity Index (GSI-SCL) of the Symptoms Checklist-90 (Revised), and Clinical Global Improvement scores (CGI). RESULTS: The RCI allowed a comparison of treatment efficacy across diagnoses. Both groups experienced similar improvement on the RCI (2.92 [±3.64] vs. 3.15 [±4.86], p = 0.65). Furthermore, 39% of OA and 42% of YA no longer met criteria for their diagnoses. Groups did not differ with respect to changes in the GSI-SCL. The CGI severity comparison suggested that OA had milder illness. In all outcomes (RCI, CGI and GSI-SCL), participants improved over time. CONCLUSIONS: This real-world study analyzed a large sample of OA and YA undergoing CBT for various mental health conditions. Both groups were found to benefit equally.

Exploring Differential Perceptions of Artificial Intelligence in Health Care Among Younger Versus Older Canadians: Results From the 2021 Canadian Digital Health Survey.

BACKGROUND: The changing landscape of health care has led to the incorporation of powerful new technologies like artificial intelligence (AI) to assist with various services across a hospital. However, despite the potential outcomes that this tool may provide, little work has examined public opinion regarding their use. OBJECTIVE: In this study, we aim to explore differences between younger versus older Canadians with regard to the level of comfort and perceptions around the adoption and use of AI in health care settings. METHODS: Using data from the 2021 Canadian Digital Health Survey (n=12,052), items related to perceptions about the use of AI as well as previous experience and satisfaction with health care were identified. We conducted Mann-Whitney U tests to compare the level of comfort of younger versus older Canadians regarding the use of AI in health care for a variety of purposes. Multinomial logistic regression was used to predict the comfort ratings based on categorical indicators. RESULTS: Younger Canadians had greater knowledge of AI, but older Canadians were more comfortable with AI applied to monitoring and predicting health conditions, decision support, diagnostic imaging, precision medicine, drug and vaccine development, disease monitoring at home, tracking epidemics, and optimizing workflow to save time. Additionally, for older respondents, higher satisfaction led to higher comfort ratings. Only 1 interaction effect was identified between previous experience, satisfaction, and comfort with AI for drug and vaccine development. CONCLUSIONS: Older Canadians may be more open to various applications of AI within health care than younger Canadians. High satisfaction may be a critical criterion for comfort with AI, especially for older Canadians. Additionally, in the case of drug and vaccine development, previous experience may be an important moderating factor. We conclude that gaining a greater understanding of the perceptions of all health care users is integral to the implementation and sustainability of new and cutting-edge technologies in health care settings.

The effectiveness of mindfulness-based meditation treatments for late life anxiety: a systematic review of randomized controlled trials.

OBJECTIVE: Older adults are interested in mindfulness-based interventions with a meditation component for late life anxiety. This review examined the effectiveness of existing mindfulness-based interventions with a meditation component. METHODS: This systematic review was registered with the Joanna Briggs Institute on 2021-05-17, was guided by Joanna Briggs Institute methodology and followed the PRISMA framework. Peer-reviewed randomized control trials were reviewed. A systematic literature search was conducted, using the following databases: MEDLINE (Ovid), Embase, Cochrane Database of Systematic Reviews, PsycINFO, CINAHL (EBSCO), and AMED. RESULTS: Of 2709 studies screened, seven eligible randomized controlled trials were included representing 355 participants. Sample sizes ranged from 36 to 141. Mindfulness-based meditation interventions used varied. Regardless of the mindfulness-based meditation intervention used, a reduction in symptoms of anxiety in participants was reported post-intervention. Results are reported through narrative summary and tables. CONCLUSIONS: Based on the emerging literature of randomized controlled trials, mindfulness-based interventions with a meditation component appear to be promising in reducing symptoms of anxiety in older adults. These findings demonstrate a need for further randomized controlled trials to guide clinical practice.

Equivalence of plasma p-tau217 with cerebrospinal fluid in the diagnosis of Alzheimer's disease.

INTRODUCTION: Plasma biomarkers are promising tools for Alzheimer's disease (AD) diagnosis, but comparisons with more established biomarkers are needed. METHODS: We assessed the diagnostic performance of p-tau181 , p-tau217 , and p-tau231 in plasma and CSF in 174 individuals evaluated by dementia specialists and assessed with amyloid-PET and tau-PET. Receiver operating characteristic (ROC) analyses assessed the performance of plasma and CSF biomarkers to identify amyloid-PET and tau-PET positivity. RESULTS: Plasma p-tau biomarkers had lower dynamic ranges and effect sizes compared to CSF p-tau. Plasma p-tau181 (AUC = 76%) and p-tau231 (AUC = 82%) assessments performed inferior to CSF p-tau181 (AUC = 87%) and p-tau231 (AUC = 95%) for amyloid-PET positivity. However, plasma p-tau217 (AUC = 91%) had diagnostic performance indistinguishable from CSF (AUC = 94%) for amyloid-PET positivity. DISCUSSION: Plasma and CSF p-tau217 had equivalent diagnostic performance for biomarker-defined AD. Our results suggest that plasma p-tau217 may help reduce the need for invasive lumbar punctures without compromising accuracy in the identification of AD. HIGHLIGHTS: p-tau217 in plasma performed equivalent to p-tau217 in CSF for the diagnosis of AD, suggesting the increased accessibility of plasma p-tau217 is not offset by lower accuracy. p-tau biomarkers in plasma had lower mean fold-changes between amyloid-PET negative and positive groups than p-tau biomarkers in CSF. CSF p-tau biomarkers had greater effect sizes than plasma p-tau biomarkers when differentiating between amyloid-PET positive and negative groups. Plasma p-tau181 and plasma p-tau231 performed worse than p-tau181 and p-tau231 in CSF for AD diagnosis.

APOEε4 potentiates the relationship between amyloid-ß and tau pathologies.

APOEε4 is the most well-established genetic risk factor for sporadic Alzheimer's disease and is associated with cerebral amyloid-ß. However, the association between APOEε4 and tau pathology, the other major proteinopathy of Alzheimer's disease, has been controversial. Here, we sought to determine whether the relationship between APOEε4 and tau pathology is determined by local interactions with amyloid-ß. We examined three independent samples of cognitively unimpaired, mild cognitive impairment and Alzheimer's disease subjects: (1) 211 participants who underwent tau-PET with [18F]MK6240 and amyloid-PET with [18F]AZD4694, (2) 264 individuals who underwent tau-PET with [18F]Flortaucipir and amyloid-PET with [18F]Florbetapir and (3) 487 individuals who underwent lumbar puncture and amyloid-PET with [18F]Florbetapir. Using a novel analytical framework, we applied voxel-wise regression models to assess the interactive effect of APOEε4 and amyloid-ß on tau load, independently of age and clinical diagnosis. We found that the interaction effect between APOEε4 and amyloid-ß, rather than the sum of their independent effects, was related to increased tau load in Alzheimer's disease-vulnerable regions. The interaction between one APOEε4 allele and amyloid-ß was related to increased tau load, while the interaction between amyloid-ß and two APOEε4 alleles was related to a more widespread pattern of tau aggregation. Our results contribute to an emerging framework in which the elevated risk of developing dementia conferred by APOEε4 genotype involves mechanisms associated with both amyloid-ß and tau aggregation. These results may have implications for future disease-modifying therapeutic trials targeting amyloid or tau pathologies.

Bipolar symptoms, somatic burden, and functioning in older-age bipolar disorder: Analyses from the Global Aging & Geriatric Experiments in Bipolar Disorder Database project.

OBJECTIVE: Literature on older-age bipolar disorder (OABD) is limited. This first-ever analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated associations among age, BD symptoms, comorbidity, and functioning. METHODS: This analysis used harmonized, baseline, cross-sectional data from 19 international studies (N = 1377). Standardized measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Global Assessment of Functioning (GAF). RESULTS: Mean sample age was 60.8 years (standard deviation [SD] 12.2 years), 55% female, 72% BD I. Mood symptom severity was low: mean total YMRS score of 4.3 (SD 5.4) and moderate-to-severe depression in only 22%. Controlled for sample effects, both manic and depressive symptom severity appeared lower among older individuals (p's < 0.0001). The negative relationship between older age and symptom severity was similar across sexes, but was stronger among those with lower education levels. GAF was mildly impaired (mean =62.0, SD = 13.3) and somatic burden was high (mean =2.42, SD = 1.97). Comorbidity burden was not associated with GAF. However, higher depressive (p < 0.0001) and manic (p < 0.0001) symptoms were associated with lower GAF, most strongly among older individuals. CONCLUSIONS: Findings suggest an attenuation of BD symptoms in OABD, despite extensive somatic burden. Depressive symptom severity was strongly associated with worse functioning in older individuals, underscoring the need for effective treatments of BD depression in older people. This international collaboration lays a path for the development of a better understanding of aging in BD.

Symptom Severity Mixity in Older-Age Bipolar Disorder: Analyses From the Global Aging and Geriatric Experiments in Bipolar Disorder Database (GAGE-BD).

OBJECTIVE: Some individuals with bipolar disorder (BD) experience manic and depressive symptoms concurrently, but data are limited on symptom mixity in older age bipolar disorder (OABD). Using the Global Aging & Geriatric Experiments in Bipolar Disorder Database, we characterized mixity in OABD and associations with everyday function. METHODS: The sample (n = 805), from 12 international studies, included cases with both mania and depression severity ratings at a single timepoint. Four mixity groups were created: asymptomatic (A), mixed (Mix), depressed only (Dep), and manic only (Man). Generalized linear mixed models used mixity group as the predictor variable; cohort was included as a random intercept. Everyday function was assessed with the Global Assessment of Functioning score. RESULTS: Group proportions were Mix (69.6%; n = 560), followed by Dep (18.4%; n = 148), then A (7.8%; n = 63), then Man (4.2%; n= 34); levels of depression and mania were similar in Mix compared to Dep and Man, respectively. Everyday function was lowest in Mix, highest in A, and intermediate in Man and Dep. Within Mix, severity of depression was the main driver of worse functioning. Groups differed in years of education, with A higher than all others, but did not differ by age, gender, employment status, BD subtype, or age of onset. CONCLUSIONS: Mixed features predominate in a cross-sectional, global OABD sample and are associated with worse everyday function. Among those with mixed symptoms, functional status relates strongly to current depression severity. Future studies should include cognitive and other biological variables as well as longitudinal designs to allow for evaluation of causal effects.

Physical Health Burden Among Older Men and Women With Bipolar Disorder: Results From the Gage-Bd Collaboration.

OBJECTIVES: To compare the prevalence of physical morbidities among men and women with older adult bipolar disorder (OABD), and men with and without OABD. METHODS: Cross-sectional analysis of the collaborative Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) database and non-OABD data from the Health in Men Study. OABD defined as bipolar disorder among adults aged greater than or equal to 50 years. Outcomes of interest were diseases affecting the cardiovascular, respiratory, gastrointestinal, renal, musculoskeletal and endocrinological systems. RESULTS: We examined 1407 participants with OABD aged 50-95 years, of whom 787 were women. More women than men showed evidence of morbidities affecting the respiratory, gastrointestinal, musculoskeletal and endocrinological systems. More men with than without OABD showed evidence of cardiovascular, renal and endocrinological diseases. CONCLUSION: GAGE-BD data showed that physical morbidities affect more women than men with OABD, and more men with than without OABD. The underlying reasons for these differences require clarification.

Demographic and clinical characteristics of lithium-treated older adults with bipolar disorder.

OBJECTIVES: There is limited information on the characteristics of older adults with bipolar disorder (OABD) treated with lithium, along with safety concerns about its use by older adults. The aim of the present study is to describe the demographic and clinical characteristics of OABD receiving lithium therapy, using data from the Global Ageing & Geriatric Experiments in Bipolar Disorder (GAGE-BD). EXPERIMENTAL PROCEDURES: Cross-sectional analysis of the GAGE-BD dataset to determine differences and similarities between lithium users and non-users. We analysed data from 986 participants aged 50 years or older (mean age 63.5 years; 57.5% females) from 12 study sites. Two subgroups ('Lithium'; 'Non-lithium') were defined according to the current prescription of lithium. We compared several outcomes between these groups, controlling for age, gender, and study site. RESULTS: OABD treated with lithium had lower scores on depression rating scales and were less likely to be categorised as with moderate or severe depression. There was a lower proportion of lithium users than non-users among those with evidence of rapid cycling and non-bipolar psychiatric diagnoses. Assessment of global cognitive state and functionality indicated better performance among lithium users. The current use of antipsychotics was less frequent among lithium users, who also reported fewer cardiovascular comorbidities than non-users. CONCLUSION: We found several potentially relevant differences in the clinical profile of OABD treated with lithium compared with those treated with other mood stabilisers. However, the interpretation of the present results must take into account the methodological limitations inherent to the cross-sectional approach and data harmonisation.

Atorvastatin lowers serum calcium levels in lithium-users: results from a randomized controlled trial.

BACKGROUND: Although lithium is considered the gold-standard treatment for bipolar disorder (BD), it is associated with a variety of major endocrine and metabolic side effects, including parathyroid hormone (PTH) dependent hypercalcemia. Aside from surgery and medication discontinuation, there are limited treatments for hypercalcemia. This paper will assess data from a randomized controlled trial (RCT). METHODS: This is a secondary analysis of an RCT that explored the effects of atorvastatin (n = 27) versus placebo (n = 33) on lithium-induced nephrogenic diabetes insipidus (NDI) in patients with BD and major depressive disorder (MDD) using lithium (n = 60), over a 12-week period. This secondary analysis will explore serum calcium levels and thyroid stimulating hormone (TSH) measured at baseline, week 4, and week 12. RESULTS: At 12-weeks follow-up while adjusting results for baseline, linear regression analyses found that corrected serum calcium levels were significantly lower in the treatment group (mean (M) = 2.30 mmol/L, standard deviation (SD) = 0.07) compared to the placebo group (M = 2.33 mmol/L, SD = 0.07) (ß = - 0.03 (95% C.I.; - 0.0662, - 0.0035), p = 0.03) for lithium users. There were no significant changes in TSH. CONCLUSION: In lithium users with relatively normal calcium levels, receiving atorvastatin was associated with a decrease in serum calcium levels. Although exciting, this is a preliminary finding that needs further investigation with hypercalcemic patients. Future RCTs could examine whether atorvastatin can treat PTH dependent hypercalcemia due to lithium and other causes.

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.