Accelerated brain aging as a biomarker for staging in bipolar disorder: an exploratory study.

BACKGROUND: Two established staging models outline the longitudinal progression in bipolar disorder (BD) based on episode recurrence or inter-episodic functioning. However, underlying neurobiological mechanisms and corresponding biomarkers remain unexplored. This study aimed to investigate if global and (sub)cortical brain structures, along with brain-predicted age difference (brain-PAD) reflect illness progression as conceptualized in these staging models, potentially identifying brain-PAD as a biomarker for BD staging. METHODS: In total, 199 subjects with bipolar-I-disorder and 226 control subjects from the Dutch Bipolar Cohort with a high-quality T1-weighted magnetic resonance imaging scan were analyzed. Global and (sub)cortical brain measures and brain-PAD (the difference between biological and chronological age) were estimated. Associations between individual brain measures and the stages of both staging models were explored. RESULTS: A higher brain-PAD (higher biological age than chronological age) correlated with an increased likelihood of being in a higher stage of the inter-episodic functioning model, but not in the model based on number of mood episodes. However, after correcting for the confounding factors lithium-use and comorbid anxiety, the association lost significance. Global and (sub)cortical brain measures showed no significant association with the stages. CONCLUSIONS: These results suggest that brain-PAD may be associated with illness progression as defined by impaired inter-episodic functioning. Nevertheless, the significance of this association changed after considering lithium-use and comorbid anxiety disorders. Further research is required to disentangle the intricate relationship between brain-PAD, illness stages, and lithium intake or anxiety disorders. This study provides a foundation for potentially using brain-PAD as a biomarker for illness progression.

Feasibility and Acceptability of Group Interpersonal and Social Rhythm Therapy for Recurrent Mood Disorders: A Pilot Study.

OBJECTIVE: Interpersonal and social rhythm therapy (IPSRT) was developed to empower patients with mood disorders by stabilizing underlying disturbances in circadian rhythms and by using strategies from interpersonal psychotherapy. Group IPSRT has not been studied with a transdiagnostic sample of patients across the life span with either major depressive disorder or bipolar disorder. METHODS: Thirty-eight outpatients, ages 26-80, with major depressive disorder or bipolar disorder in any mood state were recruited from clinics in the Netherlands and were treated with 20 sessions (two per week) of group IPSRT. Recruitment results, dropout rates, and session adherence were used to assess feasibility. The modified Client Satisfaction Questionnaire (CSQ) and a feedback session were used to measure treatment acceptability. Changes in mood symptoms, quality of life, and mastery were also measured. RESULTS: Participants' mean±SD age was 65.4±10.0 years. Participants were diagnosed as having major depressive disorder (N=14, 37%) or bipolar disorder (N=24, 63%). The dropout rate was relatively low (N=9, 24%). High CSQ scores (32.3±5.2 of 44.0 points) and low dropout rates indicated the acceptability and feasibility of group IPSRT for major depressive disorder and bipolar disorder. Quality of life 3 months after completion of treatment was significantly higher than at baseline (p<0.01, Cohen's d=-0.69). No significant differences were found between pre- and postintervention depressive symptom scores. CONCLUSIONS: Twice-weekly group IPSRT for older outpatients with major depressive disorder or bipolar disorder was feasible and acceptable. Future research should evaluate the short- and long-term efficacy of group IPSRT for major depressive disorder and bipolar disorder among patients of all ages.

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.

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.

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.

The influence of social, psychological, and cognitive factors on the clinical course in older patients with bipolar disorder.

OBJECTIVES: Research on factors that contribute to recurrence in older adults with bipolar disorder (OABD) is sparse. Previous research showed that clinical factors (e.g., age of onset, lifetime psychotic features, and suicide risk) were not associated with the recurrence in OABD. In younger adults, worse social functioning, coping style, and worse cognitive functioning are found to be associated with an unfavorable course of bipolar disorder. Therefore, this study is focusing on social, psychological, and cognitive factors in OABD. More insight in these factors is essential in order to develop and further specify preventive and treatment interventions. METHODS: Data were used from the Dutch Older Bipolars (DOBi) cohort study. We included 64 patients for 3-year follow-up measurements, who were divided in a recurrent group and a nonrecurrent group. Logistic regression analyses were conducted to assess associations between social, psychological, and cognitive factors, and nonrecurrence. RESULTS: 39.1% reported at least one recurrence during the 3-year follow-up period. No significant associations were found between the social, psychological, and cognitive factors and having a recurrence during the follow-up period. DISCUSSION: Participants in the recurrent group were younger, more often female and less likely to have children. Our results suggest that results from the adult bipolar disorder population cannot be extrapolated to OABD patients, underlining the need for longitudinal studies in OABD.

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.

Does cognitive function in older bipolar patients depend on recurrent or current mood symptoms?

BACKGROUND: Cognitive impairment in patients with bipolar disorder (BD) is viewed as an integral part of the disorder that seems to be rather stable and even present in euthymic state. Current mood symptoms influence cognition negatively and multiple mood episodes could lead to more severe psychopathology and cognitive impairment, resulting in a hypothesized neuroprogressive course of BD. The influence of current mood symptoms and recurrent mood episodes on cognitive functioning warrants further exploration. METHODS: Cohort 1 included 20 hypomanic and 21 depressed older adults with bipolar disorder (OABD) of which 20 were reassessed in the euthymic state and 50 healthy subjects. Cohort 2 included 27 OABD who had no recurrent mood episodes during 5 years and 29 who had recurrent mood episodes during 5 years. Neuropsychological examination including tests for memory, executive function, attention and verbal fluency was performed repeatedly in all subjects. RESULTS: In cohort 1 cross-sectional analyses showed that hypomanic, depressed and euthymic patients groups did not differ from each other with respect to their cognitive functioning, except for attention, which was poorer only in depressed patients. Regardless of mood state patients experienced significantly worse cognitive functioning compared to the healthy subjects. Within subject comparisons revealed that performance on memory tasks was worse in patients with current mood symptoms; depressed patients were more impaired in the learning condition and hypomanic patients were more impaired in delayed recall. In cohort 2 cognitive functioning was not different in patients with or without recurrence in 5 year follow-up. CONCLUSIONS: Although OABD had worse cognitive functioning than healthy subjects, there was a quite stable pattern of cognitive impairment, regardless of current or recurrent mood episodes. These results do not provide consistent support for the hypothesis of neuroprogression in BD.

An intervention programme for caregivers of dementia patients with frontal behavioural changes: an explorative study with controlled effect on sense of competence.

AIM: Caregivers of dementia patients experience high levels of burden; this is especially true of caregivers of dementia patients with behavioural problems. As intervention studies for these caregivers are still lacking, we conducted an explorative pilot study into the efficacy of a support programme. METHODS: Participants were caregivers of dementia patients affected by apathy, disinhibition, and/or stereotypical behaviour. All patients had a Frontal Behavioural Inventory score of 11 or higher. Caregivers were randomized to the intervention group or control group (both n = 15). The intervention was a 6-month programme that consisted of psychoeducation, social support, and behavioural cognitive therapy. Quantitative and qualitative data were collected at baseline and after the intervention. RESULTS: An increased sense of competence was found in the intervention group. Burden, perceived stress, and depressive symptoms decreased, although the difference between the intervention and control groups was not significant. CONCLUSIONS: Caregivers' sense of competence improved as a result of the support programme, and caregivers revealed its comprehensive supportive effects. Further research into the efficacy of the programme on a larger scale is recommended.

The clinical course of late-life bipolar disorder, looking back and forward.

OBJECTIVES: Little is known about the course of late-life bipolar disorder (LLBD). First, we studied patients with LLBD retrospectively with regard to age at first mood episode, onset polarity, predominant polarity and episode density and its associations with other clinical variables. Next, we examined prospectively the clinical course and its associated factors. METHODS: Data were used from a dynamic cohort (Dutch Older Bipolars [DOBi]) including 101 patients with LLBD (mean age of 68.9 years) at baseline in 2012, with 3-year follow-up measurements available for 64 of these patients. Retrospective course was assessed by diagnostic interviews, and at follow-up polarity and duration for each consecutive episode were noted. Linear and logistic analyses were performed to assess associations between relevant factors and outcome. RESULTS: The mean age at the first episode was 33.0 years. Onset polarity was depression in 44.6% of patients, with a predominant polarity of depression in 47.5%. At 3-year follow-up, 37.5% of patients reported at least one mood episode, mainly depression. Life events, somatic illness, use of lithium and other factors were not associated with recurrence during the 3-year follow-up. DISCUSSION: A relapse rate of 37.5% in 3 years is high, considering that LLBD patients generally have a longer history of disease and were receiving care and medication. The course of LLBD can provide important information on which clinical factors are associated with recurrence. Further phenotyping may reveal unique predictors for outcome, and both course specifiers and clinical variables should be included.

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.

Leptin, ghrelin and high-molecular-weight adiponectin in relation to anxiety in older adults.

BACKGROUND: Leptin and ghrelin have been linked to depressive symptoms in older adults. There is a large overlap between depression and anxiety in this group. It is unclear whether the same associations exist with anxiety. Adiponectin has an inverse association with anxiety in older adults. However, the association between the most biologically active isoform - high-molecular-weight (HMW) adiponectin - and anxiety has not been previously reported. METHODS: We analyzed the association between leptin, ghrelin and HMW adiponectin and general symptoms of anxiety (HADS-A score ≥ 7) at baseline and after three years of follow-up in a population based cohort of older adults in the Netherlands (n = 898) using multivariable logistic regression analyses. RESULTS: For leptin there was significant effect modification by sex. We found a positive association between leptin and general symptoms of anxiety in men at baseline and after three years of follow-up after adjusting for depressive symptoms, when comparing the third to the first leptin tertile (T3 vs T1 OR 3.40, 95 % CI 1.08 - 10.78). We found no significant associations for ghrelin. HMW adiponectin was associated with general symptoms of anxiety at follow up. We found a positive association both before and after adjustment for depressive symptoms (T3 vs T1 OR 3.26, 95 % CI 1.36 - 7.83). CONCLUSIONS: Our results showed significant associations in men only between leptin and HMW adiponectin and general symptoms of anxiety after three years of follow up. Our findings contribute to further insight into the pathophysiology of anxiety in older adults. However, further research is necessary as we show associations.