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.

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.

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.

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.

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.

Are Apathy and Depressive Symptoms Related to Vascular White Matter Hyperintensities in Severe Late Life Depression?

OBJECTIVE: Apathy symptoms are defined as a lack of interest and motivation. Patients with late-life depression (LLD) also suffer from lack of interest and motivation and previous studies have linked apathy to vascular white matter hyperintensities (WMH) of the brain in depressed and nondepressed patients. The aim of this study was to investigate the relationship between apathy symptoms, depressive symptoms, and WMH in LLD. We hypothesize that late-onset depression (LOD; first episode of depression after 55 years of age) is associated with WMH and apathy symptoms. METHODS: Apathy scores were collected for 87 inpatients diagnosed with LLD. Eighty patients underwent brain magnetic resonance imaging. Associations between depressive and apathy symptoms and WMH were analyzed using linear regression. RESULTS: All 3 subdomains of the 10-item Montgomery-Åsberg Depression Rating Scale correlated significantly with the apathy scale score (all P < .05). In the total sample, apathy nor depressive symptoms were related to specific WMH. In LOD only, periventricular WMH were associated with depression severity (ß = 5.21, P = .04), while WMH in the left infratentorial region were associated with apathy symptoms (ß coefficient = 5.89, P = .03). CONCLUSION: Apathy and depressive symptoms are highly overlapping in the current cohort of older patients with severe LLD, leading to the hypothesis that apathy symptoms are part of depressive symptoms in the symptom profile of older patients with severe LLD. Neither apathy nor depressive symptoms were related to WMH, suggesting that radiological markers of cerebrovascular disease, such as WMH, may not be useful in predicting these symptoms in severe LLD.

Hypothalamus-Pituitary-Adrenal-axis activity and cognitive functioning in older adults.

Inconsistent results are found in the involvement of the Hypothalamus-Pituitary-Adrenal (HPA)-axis in cognitive functioning. This study examined the association between various saliva cortisol measures (the 1-h awakening cortisol, evening cortisol, diurnal change, and cortisol suppression) and cognitive functioning (episodic memory, processing speed, interference control, and working memory). Participants were older adults, between 60 and 93 years with (N = 328) and without (N = 119) a depressive disorder from the Netherlands Study of Depression in Older adults. No significant associations between cortisol and cognitive functioning were observed in the total sample. Only in non-depressed older adults, higher total cortisol secretion over the first hour after awakening and worse episodic memory, higher cortisol levels at awakening and better working memory, and higher diurnal change and better processing speed were significantly associated. Cortisol was not associated with cognitive functioning in depressed older adults. In older adults, the association between depression and cognitive functioning is likely the consequence of other biological or psychological mechanisms.

Perceived stress and cognitive function in older adults: which aspect of perceived stress is important?

OBJECTIVE: Few studies examined the association between perceived stress and cognitive function in older adults. This study will examine which aspects of perceived stress especially impact cognitive function. METHODS: Cross-sectional data of 1099 older adults between 64 and 100 years from the Longitudinal Aging Study Amsterdam were used. Perceived stress and its subscales perceived helplessness and perceived self-efficacy were measured with the Perceived Stress Scale. Cognitive function was assessed regarding memory, processing speed and executive function. Univariate and multivariate linear regression analyses were performed between the stress measures and the domains of cognitive function. RESULTS: Perceived stress was associated with worse processing speed, direct and delayed recall, semantic fluency and digit span backwards (range ß = -0.10; -0.11; p < 0.01). The subscale perceived helplessness showed negative associations only with processing speed (ß = -0.06, p < 0.05) and delayed recall (ß = -0.06, p < 0.05), which became nonsignificant after the adjustment for depressive symptoms or sense of mastery. The subscale perceived self-efficacy was significantly associated with better cognitive function, also after adjustment for depressive symptoms or sense of mastery (range ß = 0.10; 0.18; p < 0.01). CONCLUSIONS: In older adults, especially perceived self-efficacy showed independent associations with a broad range of cognitive functions. Perceived self-efficacy might be an important factor in reducing stress and the prevention of cognitive decline. Copyright © 2016 John Wiley & Sons, Ltd.

Adverse Childhood and Recent Negative Life Events: Contrasting Associations With Cognitive Decline in Older Persons.

OBJECTIVE: To examine whether persons who experienced adverse childhood events or recent negative life events have a worse cognitive performance and faster cognitive decline and the role of depression and apolipoprotein E-∊4 in this relationship. METHODS: The community-based sample consisted of 10-year follow-up data of 1312 persons participating in the Longitudinal Aging Study Amsterdam (age range 65-85 years). RESULTS: Persons who experienced adverse childhood events showed a faster 10-year decline in processing speed but only when depressive symptoms were experienced. Persons with more recent negative life events showed slower processing speed at baseline but no faster decline. CONCLUSIONS: Childhood adversity may cause biological or psychological vulnerability, which is associated with both depressive symptoms and cognitive decline in later life. The accumulation of recent negative life events did not affect cognitive functioning over a longer time period.

Heterogeneity of late-life depression: relationship with cognitive functioning.

BACKGROUND: Late-life depression is a heterogeneous disorder, whereby cognitive impairments are often observed. This study examines which clinical characteristics and symptom dimensions of late-life depression are especially impacting on specific cognitive domains. METHODS: Cross-sectional data of 378 depressed and 132 non-depressed older adults between 60-93 years, from the Netherlands Study of Depression in Older adults (NESDO) were used. Depressed older adults were recruited from both inpatient and outpatient mental healthcare institutes and general practices, and diagnosed according to DSM-IV-TR criteria. Multivariable associations were examined with depression characteristics (severity, onset, comorbidity, psychotropic medication) and symptom dimensions as independent variables and cognitive domains (episodic memory, processing speed, interference control, working memory) as dependent variables. RESULTS: Late-life depression was associated with poorer cognitive functioning. Within depressed participants, higher severity of psychopathology and having a first depressive episode was associated with poorer cognitive functioning. The use of tricyclic antidepressants, serotonergic and noradrenergic working antidepressants, and benzodiazepines was associated with worse cognitive functioning. Higher scores on the mood dimension were associated with poorer working memory and processing speed, whereas higher scores on a motivational and apathy dimension were associated with poorer episodic memory and processing speed. CONCLUSIONS: Heterogeneity in late-life depression may lead to differences in cognitive functioning. Higher severity and having a first depressive episode was associated with worse cognitive performance. Additionally, different domains of cognitive functioning were associated with specific symptom dimensions. Our findings on the use of psychotropic medication suggest that close monitoring on cognitive side effects is needed.

Mediators of the relationship between life events and memory functioning in a community sample of adults.

The present study examines the association of frequency and severity of life events with memory functioning in a community sample of adults. We tested the hypothesis that stress-related cognitive interference mediated the effects of recent life events on cognition, in addition to examining the potential roles of fatigue, sleep disturbances, and depression. The sample consisted of 310 adults (age range 19-83) who received a battery of cognitive tests assessing their primary memory, episodic memory, and working memory. Individuals rated how stressful previous life events were when they occurred, as well as how stressful the events were for them currently. Ratings of current, but not past severity were negatively associated with working memory performance. Both stress-related cognitive interference and depressive symptoms independently mediated this association. These findings highlight the importance of intrusive and avoidant thinking as a potential focus of psychosocial treatment for remediating stress-related memory dysfunction.

Early and late onset depression in young and middle aged adults: differential symptomatology, characteristics and risk factors?

BACKGROUND: Early onset depression (EOD) and late onset depression (LOD) may be different phenomena. In this study, differences between EOD and LOD in symptomatology, psychiatric characteristics and psychosocial/somatic factors were examined. METHODS: Baseline data were from 1104 participants with a current major depressive disorder participating in the Netherlands Study of Depression and Anxiety (age range 18-65 years). DSM-IV diagnoses, depressive symptoms and age of onset were assessed with the Composite International Diagnostic Interview. Analyses were performed by using a continuous as well as a dichotomous (cut-off 40 years) age of onset indicator. RESULTS: Differences between EOD and LOD were observed: longer duration of symptoms (p<.001), a personal history of depressive episodes (p<.001), a serious suicide attempt (p<.001), childhood events (p<.001), a family history of depression (p=.03), and high neuroticism (p<.001) were more often present in EOD than in LOD. Also differences in symptomatology were observed: feelings of sadness (p<.001), diminished concentration (p=.02) and suicidal thoughts (p=.001) were significantly less prevalent at a higher age of onset, whereas decreased appetite/weight loss (p=.01) was more prominent at a higher age of onset. LIMITATIONS: The age of first depression onset was asked retrospectively and might be biased by selective recall. However, participants can likely recall whether symptoms started earlier or later in life. CONCLUSIONS: Despite similarities, our observed differential findings in symptoms, psychiatric characteristics, and psychosocial factors between EOD and LOD further support that EOD is associated with more frequent occurrence of some clinical features of depression. These differential findings are important factors to keep in mind for diagnostics, treatment, and prevention.