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.

Social cognition differentiates phenocopy syndrome of behavioural variant frontotemporal dementia from behavioural variant frontotemporal dementia.

BACKGROUND: Patients displaying clinical features of behavioural variant of frontotemporal dementia (bvFTD) but lacking both neuroimaging abnormalities and clinical progression are considered to represent the phenocopy syndrome of bvFTD (phFTD). Extensive clinical overlap between early phase bvFTD and phFTD hampers diagnostic distinction. We aimed to assess the diagnostic value of clinician-rated, self-reported and caregiver-reported symptoms for clinical distinction between phFTD and bvFTD. METHODS: There were 33 phFTD and 95 probable bvFTD patients included in the study (total N = 128). Clinician-rated, self-reported tests and caregiver-reported symptoms were compared between phFTD and bvFTD on social cognition, behaviour, mood and activities of daily living (ADL). Scores were compared between groups, followed by multiple logistic regression analysis, adjusted for age and sex. Receiver operating characteristic curves were plotted to assess diagnostic value. RESULTS: Using clinician-rated and self-reported tests, phFTD patients performed better on facial emotion recognition and reported more depressive symptoms. Caregiver-reported behavioural symptoms indicated higher behavioural and ADL impairment in phFTD compared to bvFTD. Facial emotion recognition provided highest diagnostic accuracy for distinction of phFTD from bvFTD (area under the curve (AUC) 0.813 95% CI 0.735-0.892, P < 0.001, sensitivity 81%, specificity 74%) followed by depressive symptoms (AUC 0.769 95% 0.674-0.864, P < 0.001 sensitivity 81%, specificity of 63%). CONCLUSION: Social cognition tests are most suitable for distinction of phFTD from bvFTD. Caregiver-reported questionnaires and phFTD diagnosis seemed inversely correlated, showing more symptoms in phFTD. Further research is needed on phFTD aetiology and in caregivers taking into account disease burden to assess what explains this discrepancy between clinician-rated and caregiver-based tools.

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.

Diagnostic Instability Over Time in the Late-Onset Frontal Lobe Syndrome: When Can We Say it's FTD?

OBJECTIVES: Distinguishing sporadic behavioral variant of frontotemporal dementia (bvFTD) from late-onset primary psychiatric disorders (PPD) remains challenging with the lack of robust biomarkers. An early bvFTD misdiagnosis in PPD cases and vice-versa is common. Little is known about diagnostic (in)stability over longer period of time. We investigated diagnostic instability in a neuropsychiatric cohort up to 8 years after baseline visit and identified which clinical hallmarks contribute to diagnostic instability. DESIGN: Diagnoses of participants of the late-onset frontal lobe (LOF) study were collected from the baseline visit (T0) and the 2-year follow-up visit (T2). Clinical outcomes were retrieved 5-8 years after baseline visit (Tfinal). Endpoint diagnoses were categorized into bvFTD, PPD and other neurological disorders (OND). We calculated the total amount of participants that switched diagnosis between T0-T2 and T2-Tfinal. Clinical records of participants that switched diagnosis were assessed. RESULTS: Of the 137 patients that were included in the study, the final diagnoses at Tfinal were bvFTD 24.1% (n = 33), PPD 39.4% (n = 54), OND 33.6% (n = 46) and unknown 2.9% (n = 4). Between T0 and T2, a total of 29 (21.2%) patients switched diagnosis. Between T2 and Tfinal, 8 (5.8%) patients switched diagnosis. Prolonged follow-up identified few cases with diagnostic instability. Major contributors to diagnostic instability where a nonconverting diagnosis of possible bvFTD and a probable bvFTD diagnosis based on informant-based history and an abnormal FDG-PET scan whilst having a normal MRI. CONCLUSION: Considering these lessons, a FTD diagnosis remains stable enough to conclude that 2 years is sufficient to say if a patient with late-life behavioral disorder has FTD.

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.

Cognition in older adults with bipolar disorder: An ISBD task force systematic review and meta-analysis based on a comprehensive neuropsychological assessment.

OBJECTIVES: We aim to characterize the cognitive performance in euthymic older adults with bipolar disorder (OABD) through a comprehensive neuropsychological assessment to obtain a detailed neuropsychological profile. METHODS: We conducted a systematic search in MEDLINE/Pubmed, Cochrane, and PsycInfo databases. Original studies assessing cognitive function in OABD (age ≥50 years ) containing, at a minimum, the domains of attention/processing speed, memory, and executive functions were included. A random-effects meta-analysis was conducted to summarize differences between patients and matched controls in each cognitive domain. We also conducted meta-regressions to estimate the impact of clinical and socio-demographic variables on these differences. RESULTS: Eight articles, providing data for 328 euthymic OABD patients and 302 healthy controls, were included in the meta-analysis. OABD showed worse performance in comparison with healthy controls, with large significant effect sizes (Hedge's g from -0.77 to -0.89; p < 0.001) in verbal learning and verbal and visual delayed memory. They also displayed statistically significant deficits, with moderate effect size, in processing speed, working memory, immediate memory, cognitive flexibility, verbal fluency, psychomotor function, executive functions, attention, inhibition, and recognition (Hedge's g from -0.52 to -0.76; p < 0.001), but not in language and visuoconstruction domains. None of the examined variables were associated with these deficits. CONCLUSIONS: Cognitive dysfunction is present in OABD, with important deficits in almost all cognitive domains, especially in the memory domain. Our results highlight the importance of including a routine complete neuropsychological assessment in OABD and also considering therapeutic strategies in OABD.

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.

Long-term Outcome Following Electroconvulsive Therapy for Late-Life Depression: Five-Year Follow-up Data From the MODECT Study.

OBJECTIVE: Electroconvulsive therapy (ECT) is the most effective treatment for late-life depression (LLD). Research addressing long-term outcome following an acute course of ECT for LLD is limited. We aimed to describe relapse, cognitive impairment and survival 5 years after a treatment with ECT for severe LLD, and assess the association of clinical characteristics with all three outcome measures. METHODS: This cohort study was part of the Mood Disorders in Elderly treated with ECT (MODECT) study, which included patients aged 55 years and older with major depressive disorder. Data regarding clinical course, cognitive impairment and mortality were collected 5 years after the index ECT course. We used multivariable Cox proportional hazards models and logistic regression models to assess the association of clinical characteristics with relapse and survival, and cognitive impairment, respectively. RESULTS: We studied 110 patients with a mean age of 72.9 years. 67.1% of patients who showed response at the end of the index ECT course relapsed, and the included clinical characteristics were not significantly associated with the risk of relapse. 38.8% of patients with available data showed cognitive impairment at five-year follow-up. 27.5% were deceased; higher age and a higher number of previous psychiatric admissions were significantly associated with increased risk of mortality. CONCLUSIONS: Five-year outcome after a course of ECT for severe LLD seems to be in line with long-term outcome following other acute treatments for severe LLD in terms of relapse, cognitive impairment and survival. Additional studies aimed at improving long-term outcome in severe LLD are warranted.

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.

Is social functioning in older age patients with bipolar disorder associated with affective and/or non-affective cognition?

OBJECTIVES: Previous research showed impairments in non-affective cognition, affective cognition, and social functioning in adult patients with bipolar disorder (BD). Only 37% of adult BD patients recovers in social functioning, and both aspects of cognition are important constructs of influence. The role of affective cognition in older age bipolar disorder (OABD) patients is still unclear. Therefore, the aim of our study was to examine the separate and combined effects of affective cognition and non-affective cognition on social functioning. METHODS: The current study included 60 euthymic patients (aged >60) of the Dutch Older Bipolar Study. Affective cognition was measured by Theory of Mind and Emotion Recognition. Non-affective cognition was assessed through the measurements of attention, learning and memory, and executive functioning. Social functioning was examined through global social functioning, social participation, and meaningful contacts. The research questions were tested with linear and ordinal regression analyses. RESULTS: Results showed a positive association of all non-affective cognitive domains with global social functioning. Associations between affective cognition and social functioning were non-significant. Results did show an interaction between non-affective and affective cognition. CONCLUSIONS: Associations between non-affective cognition and social functioning were confirmed, associations between affective cognition and social function were not found. For generalizability, studies with a greater sample size are needed. Conducting additional research about OABD patients and affective cognition is important. It may lead to more insight in impairment and guide tailored treatment that focusses more on all aspects of recovery and the needs of OABD patients.

Illness progression in older-age bipolar disorder: Exploring the applicability, dispersion, concordance, and associated clinical markers of two staging models for bipolar disorder in an older population.

OBJECTIVES: The validity and applicability of two existing staging models reflecting illness progression have been studied in bipolar disorder (BD) in adults, but not in older adult populations. Staging model A is primarily defined by the number and recurrence of mood episodes, model B is defined by the level of inter-episodic functioning. This study aimed to explore the applicability, dispersion, and concordance of, and associations with clinical markers in these two staging models in older-age bipolar disorder (OABD). METHODS: Using cross-sectional data from the Dutch Older Bipolars study, OABD outpatients (N = 126, ≥50 years) were staged using models A and B. Dispersion over the stages and concordance between the models were assessed. Associations were explored between model stages and clinical markers (familial loading, childhood abuse, illness duration, episode density, treatment resistance, Mini-Mental State Examination, and composite cognitive score). RESULTS: Ninety subjects could be assigned to model A, 111 to model B, 80 cases to both. The majority (61%) had multiple relapses (model A, stage 3C) but were living independently (model B, stage I-III). Concordance between models was low. For model A, the markers childhood abuse, illness duration, and episode density significantly increased over subsequent stages. Model B was not associated with a significant change in any marker. CONCLUSIONS: Assigning stages to OABD subjects was possible for both models, with age-related adjustments for model B. Model B as currently operationalized may be less suitable for OABD or may measure different aspects of illness progression, reflected by its low correspondence with model A and lack of associated clinical markers.

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.

Transient Cognitive Impairment and White Matter Hyperintensities in Severely Depressed Older Patients Treated With Electroconvulsive Therapy.

BACKGROUND: Although electroconvulsive therapy (ECT) is a safe and effective treatment for patients with severe late life depression (LLD), transient cognitive impairment can be a reason to discontinue the treatment. The aim of the current study was to evaluate the association between structural brain characteristics and general cognitive function during and after ECT. METHODS: A total of 80 patients with LLD from the prospective naturalistic follow-up Mood Disorders in Elderly treated with Electroconvulsive Therapy study were examined. Magnetic resonance imaging scans were acquired before ECT. Overall brain morphology (white and grey matter) was evaluated using visual rating scales. Cognitive functioning before, during, and after ECT was measured using the Mini Mental State Examination (MMSE). A linear mixed-model analysis was performed to analyze the association between structural brain alterations and cognitive functioning over time. RESULTS: Patients with moderate to severe white matter hyperintensities (WMH) showed significantly lower MMSE scores than patients without severe WMH (F(1,75.54) = 5.42, p = 0.02) before, during, and post-ECT, however their trajectory of cognitive functioning was similar as no time × WMH interaction effect was observed (F(4,65.85) = 1.9, p = 0.25). Transient cognitive impairment was not associated with medial temporal or global cortical atrophy (MTA, GCA). CONCLUSION: All patients showed a significant drop in cognitive functioning during ECT, which however recovered above baseline levels post-ECT and remained stable until at least 6 months post-ECT, independently of severity of WMH, GCA, or MTA. Therefore, clinicians should not be reluctant to start or continue ECT in patients with severe structural brain alterations.

Cognitive performance in older-age bipolar disorder: Investigating psychiatric characteristics, cardiovascular burden and psychotropic medication.

OBJECTIVE: This study aimed to explore a large range of candidate determinants of cognitive performance in older-age bipolar disorder (OABD). METHODS: A cross-sectional study was performed in 172 BD patients aged ≥50 years. Demographics, psychiatric characteristics and psychotropic medication use were collected using self-report questionnaires and structured interviews. The presence of cardiovascular risk factors was determined by combining information from structured interviews, physical examination and laboratory assessments. Cognitive performance was investigated by an extensive neuropsychological assessment of 13 tests, covering the domains of attention, learning/ memory, verbal fluency and executive functioning. The average of 13 neuropsychological test Z-scores resulted in a composite cognitive score. A linear multiple regression model was created using forward selection with the composite cognitive score as outcome variable. Domain cognitive scores were used as secondary outcome variables. RESULTS: The final multivariable model (N = 125), which controlled for age and education level, included number of depressive episodes, number of (hypo)manic episodes, late onset, five or more psychiatric admissions, lifetime smoking, metabolic syndrome and current use of benzodiazepines. Together, these determinants explained 43.0% of the variance in composite cognitive score. Late onset and number of depressive episodes were significantly related to better cognitive performance whereas five or more psychiatric admissions and benzodiazepine use were significantly related to worse cognitive performance. CONCLUSION: Psychiatric characteristics, cardiovascular risk and benzodiazepine use are related to cognitive performance in OABD. Cognitive variability in OABD thus seems multifactorial. Strategies aimed at improving cognition in BD should include cardiovascular risk management and minimizing benzodiazepine use.

Psychiatric symptoms during the COVID-19 outbreak in older adults with bipolar disorder.

OBJECTIVES: Older adults with bipolar disorder (OABD) are vulnerable for a COVID-19 infection via multiple pathways. It is essential for OABD to adhere to the COVID-19 measures, with potential consequences for the psychiatric symptoms. This situation offers the unique opportunity to investigate factors of vulnerability and resilience that are associated with psychiatric symptoms in OABD. METHODS: This study included 81 OABD patients aged over 50 years. Factors measured at baseline in patients that participated in 2017/2018 were compared with factors measured during the COVID-19 outbreak. RESULTS: Participants experienced less psychiatric symptoms during COVID-19 than (67.9% euthymic) than at baseline (40.7% euthymic). There was no difference in loneliness between COVID-19 and baseline. Not having children, more feelings of loneliness, lower mastery, passive coping style and neuroticism were associated with more psychiatric symptoms during COVID-19 measures. CONCLUSIONS: Participants experienced less psychiatric symptoms during COVID-19 measures when compared to baseline. Our results indicate promising targets for psychological interventions aimed at curing and preventing recurrence in OABD and improving quality of life in this growing vulnerable group.