Netherlands Study Of Depression In Older Persons Research Articles

Determinants and consequences of polypharmacy in patients with a depressive disorder in later life.

ObjectivesPolypharmacy and late‐life depression often congregate in the geriatric population. The primary objective is to identify determinants of polypharmacy in patients with depression, and second to examine polypharmacy in relation to various clinical phenotypes of depression and its course.MethodsA longitudinal observational study using data of the Netherlands Study of Depression in Older persons (NESDO) including 375 patients with depression ≥ 60 years and 132 non‐depressed comparisons. Linear and logistic regression were used to analyze both polypharmacy (dichotomous: ≥5 medications) and number of prescribed drugs (continuous) in relation to depression, various clinical phenotypes, and depression course.ResultsPolypharmacy was more prevalent among patients with depression (46.9%) versus non‐depressed comparisons (19.7%). A lower level of education, lower cognitive functioning, and more chronic diseases were independently associated with polypharmacy. Adjusted for these determinants, polypharmacy was associated with a higher level of motivational problems, anxiety, pain, and an earlier age of onset. A higher number of drugs was associated with a worse course of late‐life depression (OR = 1.24 [95% CI: 1.03–1.49], p = 0.022).ConclusionOlder patients with depression have a huge risk of polypharmacy, in particular among those with an early onset depression. As an independent risk factor for chronic depression, polypharmacy needs to be identified and managed appropriately. Findings suggest that depression moderates polypharmacy through shared risk factors, including motivational problems, anxiety, and pain. The complex interaction with somatic health burden requires physicians to prescribe medications with care.

Does Late-Life Depression Counteract the Beneficial Effect of Physical Activity on Cognitive Decline? Results From the NESDO Study.

Depression both affects physical activity (PA) and cognition in older persons, yet its impact on the association between PA and cognitive decline is to be determined. We aimed to investigate the association between baseline PA and cognitive functioning over time, stratified for depression. We used data of the Netherlands Study of Depression in Older persons (NESDO), a multi-site cohort study with 6-years follow-up. Patients with complete data on PA and cognitive functioning at baseline were included, yielding 394 participants for the analyses of whom 297 were depressed and 97 non-depressed. PA (continuous) was measured with the International Physical Activity Questionnaire. Linear mixed models were used to determine differential effects of baseline PA on the rate of decline of 5 standardized outcomes of cognitive functioning over 6-year follow-up. For this purpose, we examined the significance of the interaction-term (PA*time) in both basic and adjusted models. We also assessed the association between time and cognitive functioning. All analyses were stratified for depression. In both groups, no robust significant interactions of PA with time were found. Furthermore, only decline in working memory was significantly worse in the depressed compared to the non-depressed. At older age, the impact of a more inactive lifestyle on cognitive decline was shown to be limited, irrespective of depression that appeared to worsen age-related decline of working memory only. As a higher PA-level at older age has a positive effect on a multitude of other health outcomes, PA should still be encouraged in this population.

Anxiety in Late-Life Depression: Determinants of the Course of Anxiety and Complete Remission

ObjectiveStudies on the course of depression often ignore comorbid anxiety disorders or anxiety symptoms. We explored predictors of complete remission (no depression nor anxiety diagnoses at follow-up) and of the course of comorbid anxiety symptoms. We additionally tested the hypothesis that the course of anxiety disorders and symptoms in depressed patients is explained by negative life-events in the presence of high neuroticism or a low sense of mastery. MethodsAn observational study of 270 patients (≥60 years) diagnosed with major depressive disorder and 2-year follow-up data, who participated in the Netherlands Study of Depression in Older persons (NESDO). Sociodemographic, somatic, psychiatric, and treatment variables were first explored as possible predictors. A multiple logistic regression analysis was used to examine their predictive value concerning complete remission. Subsequently, negative life-events, personality and their interaction were tested as potential predictors. Linear Mixed Models were used to assess whether the personality traits modified the effect of early and recent life-events, and time and their interactions on the course of the anxiety symptoms. ResultsA total of 135 of 270 patients achieved complete remission. Depressed patients with a comorbid anxiety disorder at baseline less often achieved complete remission: 38 of 103 (37.0%) versus 97 of 167 (58.1%). The severity of depressive and anxiety symptomatology, the presence of a comorbid anxiety disorder, and a poorer physical health at baseline predicted nonremission. In line with our hypothesis, a less favorable course of self-reported anxiety symptoms was associated with more recent negative life-events, but only among patients with a high level of neuroticism or a low level of mastery. ConclusionComorbid anxiety in depression as a negative impact on complete remission at 2-year follow-up. The course of anxiety severity seems dependent on the interaction of personality traits and life-events.

328 - Depression as a disorder of accelerated ageing

Presenting author:Prof.dr. Richard C. Oude Voshaar, University of Groningen, The Netherlands (r.c.oude.voshaar@umcg.nl)Co-author:Prof.dr. Ivan Aprahamian, Faculty of Medicine of Jundiaí, Brazil (ivan.aprahamian@gmail.com)Depressive disorder has been conceptualised as a disorder of accelerated ageing. Furthermore, meta - analyses have shown that depression associated with excess mortality, although most studies can be criticised for insufficient confounder control. These characteristics of depression resemble the characteristics of biomedical frailty. Biomedical frailty can be assessed with the frailty index (FI) based on the deficit accumulation model. This model postulates that the proportion of at least 30 ageing-related health deficits reflects biological age on top of chronological age. The characteristics of the FI are independent of the specific health deficits included, as long as health deficits from different physiological systems are included. The FI is the most accurate frailty model for predicting mortality, the ultimate outcome of increasing frailty states. Because of its continuous nature, the FI is sensitive to change which enables us to study trajectories of frailty.The objective of the present lecture is 1) to show that depressive disorder associated with accelerated biological ageing as indexed by the frailty index, 2) that depressive disorder is a risk factor for excess mortality, and 3) to show that this latter explanation is largely explain by biomedical frailty.The Netherlands Study of Depression in Older persons (NESDO) is a clinical cohort of 378 depressed patients according to DSM-IV criteria and 132 non-depressed controls who have been followed up for six-year. The data of this cohort study enabled us to construct a frailty index based on 41 non-depression related health deficits. Linear mixed models showed that the frailty index had a significantly steeper increase over six years among depressed patients compared to their non-depressed counterparts.Subsequently, we constructed a frailty index based on 64 health deficits in the LifeLines cohort study, a three-generation population-based study including 167,000 persons. In this population-based cohort, we replicated our finding that the presence of a depressive disorder according to DSM-IV criteria, but also anxiety disorders, were associated with an accelerated increase of the frailty index over a 5-year follow-up. Furthermore, Cox-regression showed that the presence of a depressive disorder or any anxiety disorder was also associated with excess mortality over a 10-year follow-up. These effects remained significant when adjusted for socio-demographic characteristics, lifestyle variables and multimorbidity, but disappeared when adjusted for the frailty index.We conclude that depressive disorder can indeed be conceptualised as a disorder of accelerated biological ageing, as indexed by the frailty index. Moreover, biomedical frailty may be an explanatory factor for excess mortality found to be associated with affective disorders. Therefore, biomedical frailty seems a promising marker for risk stratification in geriatric psychiatry.

334 - Diagnostic complexities of the differential diagnosis between biomedical frailty and depression

Presenting author:Prof.dr. Richard C. Oude Voshaar, University of Groningen, The Netherlands (r.c.oude.voshaar@umcg.nl)Co-authors:Miss Astrid Lugtenburg, GGZ Drenthe Mental Health Institute, Assen, The Netherlands (astridlugtenburg@gmail.com)Miss Marij Zuidersma, University of Groningen, The Netherlands (m.a.zuidersma@umcg.nl)The Netherlands Study of Depression in Older persons (NESDO) is a clinical cohort study including 378 older persons suffering from a depressive disorder and a comparison group of 132 never depressed older persons. Within NESDO cohort, we examined the impact of the Fried Frailty Phenotype and its criteria on the two-year course of late-life depression.With respect to the prognosis of depression, frail-depressed older patients had a significantly higher level of depressive symptoms over the course of two-years and were less often in remission at the two-year follow-up. Paradoxically, the improvement of the severity of depressive symptoms were larger in frail-depressed compared to non-frail-depressed patients. This raises the question whether the remaining symptoms should be considered as residual depressive symptoms (in need of psychiatric treatment) or physical frailty (in need of geriatric rehabilitation).To address this latter issue, we have searched for data-driven depressive subgroups by conducting a latent profile analysis on the subscales of the Inventory of Depressive Symptomatology Self Report (IDS-SR), cognitive performance (processing speed, interference, working and verbal memory) and physical frailty (gait speed, handgrip strength). Half of the depressed patients were suffering from a pure depressive disorder (consisting of two subgroups being either mildly or severely depressed), whereas the other half of the sample consisted of three different subgroups of frail-depressed patients, namely a subgroup suffering from amnestic depression, a subgroup of physically dominated frail-depressed patients and finally a subgroup of cognitively dominated frail-depressed subgroup. The three frail -depressed subgroups had differential outcomes with respect to depressive symptom severity, course of frailty parameters and mortality.

Stability and transition of depression subtypes in late life

BackgroundThe heterogeneity of late-life depression hampers diagnosis and treatment. Data-driven methods have identified several subtypes of depression in older persons, but the longitudinal stability of these subtypes remains unknown. MethodsIn total 111 older persons with a major depressive disorder both at baseline and 2-year follow-up from the Netherlands Study of Depression in Older persons (NESDO) were included. Latent class analysis was performed to identify subtypes of depression at baseline and at 2-year follow-up, and latent transition analysis was used to examine the stability of these subtypes over time. Transition rates between subtypes and characteristics of groups were examined. ResultsTwo subtypes were identified in both baseline (T0) and follow-up data (T1), including a ‘melancholic’ subtype (prevalence 80.2% (T0) and 62.2% (T1)), and an ‘atypical’ subtype (prevalence 19.8% (T0) and 37.8% (T1)). The melancholic subtype was characterized by decreased appetite and weight and had a stability of 0.86. The atypical subtype was characterized by increased appetite and weight and had a stability of 0.93, although the discriminating power of different symptoms had decreased at T1. Mean age and education differed significantly between stable and transitioning subgroups, other characteristics did not differ between subgroups. LimitationsLimited sample size might have hampered the analyses. ConclusionsSubtypes of late-life depression are relatively stable, but symptoms of depression (like weight loss) seem to blur with symptoms of (patho)physiological aging. This underlines the clinical relevance of depression subtyping, but also the importance of further research into subtypes and the influence of aging.

'Big Five' personality characteristics are associated with loneliness but not with social network size in older adults, irrespective of depression.

Loneliness and social isolation have negative health consequences and are associated with depression. Personality characteristics are important when studying persons at risk for loneliness and social isolation. The objective of this study was to clarify the association between personality factors, loneliness and social network, taking into account diagnosis of depression, partner status and gender. Cross-sectional data of an ongoing prospective cohort study, the Netherlands Study of Depression in Older Persons (NESDO), were used. 474 participants were recruited from mental health care institutions and general practitioners in five different regions in the Netherlands. NEO-Five Factor Inventory (NEO-FFI) personality factors and loneliness and social network were measured as well as possible confounders. Multinominal logistic regression analyses were performed to analyse the associations between NEO-FFI factors and loneliness and social network. Interaction terms were investigated for depression, partner status and gender. Higher neuroticism and lower extraversion in women and lower agreeableness in both men and women were associated with loneliness but not with social network size irrespective of the presence of depression. In the non-depressed group only, lower openness was associated with loneliness. Interaction terms with partner status were not significant. Personality factors are associated with loneliness especially in women. In men lower agreeableness contributes to higher loneliness. In non-depressed men and women, lower openness is associated with loneliness. Personality factors are not associated with social network size.

Prognostic effect of serum BDNF levels in late-life depression: Moderated by childhood trauma and SSRI usage?

BackgroundBrain-derived neurotrophic factor (BDNF) levels decline during depression and normalise after remission, although studies in older patient samples are inconsistent. Whether BDNF serum levels predict depression remission is unclear. We hypothesize that the predictive value of serum BDNF levels in late-life depression is moderated by selective serotonin reuptake inhibitors (SSRI) usage and early traumatization. MethodsOur study sample was a subset of the Netherlands Study of Depression in Older persons (NESDO), a prospective cohort study. It consisted of 267 older persons with a diagnosis of depression, for which follow-up data were available. Depression diagnosis was assessed at baseline and follow up using a structured diagnostic interview (Composite International Diagnostic Interview (CIDI), volume2.1). Logistic regression was performed (adjusted for covariates) with remission of depression after two years as the dependent variable and baseline BDNF serum levels, childhood traumatization and SSRI use as independent variables. Results - The mean age of the subjects was 70.7 years, 65.6% of them were female, their mean BDNF level was 7.7 ng/ml, 80 (30.0%) of them were traumatised in their childhood,71 (26.6%) used SSRIs and 136 (50.9%) no longer had a depressive disorder at the two year follow up. The predictive value of BDNF serum levels was conditional on traumatization and SSRI usage (threeway interaction p = .010). Higher BDNF serum levels predicted remission in traumatized depressed patients without SSRI usage (OR = 1.17, 95% C.I.: 1.00–1.36; p = .048) and in non-traumatized depressed patients who used SSRIs (OR = 1.17, 95% C.I.: 1.00–1.36; p = .052), but not in the other two subgroups. ConclusionThe association between BDNF serum levels and the course of late-life depression seems to depend on SSRI use and childhood trauma. Based on these results, we hypothesize that childhood trauma may permanently reduce (‘blunt’) the responsiveness of the neurotrophic system to SSRI usage, and that this responsiveness might be more important for depression course than the actual BDNF serum levels.

Vitamin D deficiency and course of frailty in a depressed older population

Objective: To study the association between vitamin D levels and frailty, its components and course in a depressed sample.Methods: Baseline and two-year follow-up data from the depressed sample of the Netherlands Study of Depression in Older persons (NESDO), a prospective observational cohort study, were analyzed. The 378 participants (aged 60–93) had a diagnosis of depression according to DSM-IV criteria. Frailty was defined according to Fried’s physical phenotype. 25-OH vitamin D measurement was performed by liquid chromatography – tandem mass spectrometry. Linear and logistic regression analyses were performed, adjusted for covariates.Results: Higher vitamin D levels were cross-sectionally associated with lower prevalence of frailty (OR 0.64 [95%-CI 0.45 – 0.90], p = .010), predicted a lower incidence of frailty among non-frail depressed patients (OR 0.51 [95%-CI 0.26 – 1.00], p=.050), and, surprisingly, the persistence of frailty among frail depressed patients (OR 2.82 [95%-CI 1.23 – 6.49], p=.015).Conclusions: In a depressed population, higher vitamin D levels were associated with lower prevalence and incidence of frailty. Future studies should examine whether the favorable effect of low vitamin D levels on the course of frailty can be explained by confounding or whether unknown pathophysiological mechanisms may exert protective effects.

Inflammation in older subjects with early- and late-onset depression in the NESDO study: a cross-sectional and longitudinal case-only design

ObjectiveDifferent biological mechanisms may underlie depression beginning in early life (early-onset) and depression beginning later in life (late-onset). Although the relation between inflammation and depression has been studied extensively, the distinct role of inflammation in early and late-onset depression in older patients has not been addressed before. In the cross-sectional part of this study, we explored differences in levels of circulating inflammatory markers and cytokine levels in lipopolysaccharide (LPS) stimulated whole blood between older subjects with a late-life onset depression (≥60 years) and older subjects with an early-onset depression (<60 years). Secondly, in a 2-year follow-up study, we examined if circulating and stimulated inflammatory markers influenced the change in Inventory of Depressive Symptomatology (IDS) scores, and if this relation was different for early- and late-onset depression. MethodsThe study was part of the Netherlands Study of Depression in Older Persons (NESDO). We included 350 patients, all aged 60 and older, with a depressive episode in the previous 6 months: 119 with a late-onset depression and 231 with an early-onset depression. Blood samples were collected and CRP, IL-6, NGAL, GDF15, and, LPS plasma levels were determined and whole blood was LPS stimulated and cytokine levels IL-1β, IL-6, TNFα, IFNγ, IL-10, and IL-1 receptor antagonist (IL-1ra) were determined. ResultsAfter adjustment for demographics, health indicators, and medication use, increased plasma CRP levels were more strongly associated with late-onset depression than early-onset depression (OR [95% CI]: 1.43 [1.05–1.94]). In the longitudinal analyses, higher circulating IL-6 levels were associated with a significantly slower decline in IDS scores in the crude and the adjusted models (p ≤ 0.027). This relation was not different between late- and early-onset depression. Other circulating and stimulated inflammatory markers were not associated with late- and/or early-onset depression. ConclusionsThis study provides preliminary evidence that low-grade inflammation is more strongly associated with late-onset than early-onset depression in older adults, suggesting a distinct inflammatory etiology for late-onset depression. Cytokine production capacity did not distinguish between early- and late-onset depression.

Reliability of retrospective reports on childhood abuse and its determinants in older adults during a 6-year follow-up

Controversy exists concerning the reliability of retrospective self-reports on childhood abuse since this method might be subject to under- or overreporting. Until now, no studies have been done in older adults, although reasons for under- or overreporting could be even more prominent in this age group. In this first study in older adults, test-retest reliability of retrospective measurements on childhood abuse and the influence of age, cognitive functioning and depression on this test-retest reliability was investigated. A longitudinal cohort study, the Netherlands Study of Depression in Older persons (NESDO), obtained information on childhood abuse at baseline and at a 6-year follow-up interview. Our sample consisted of 277 adults (mean age 68.5 years at baseline) of which 118 (42.6%) reported childhood abuse at baseline. The largest proportion of the answers was consistent (yes-yes or no-no) for every type of childhood abuse, varying from 85.2 to 93.5%. Looking more closely, ‘yes’ answers were more fluctuating than ‘no’ answers. Sexual abuse was most reliably reported in two separate interviews. There was no significant effect of age nor cognition on the test-retest reliability. Only test-retest reliability of emotional neglect was significantly associated with depression diagnosis and depression severity at baseline. In conclusion, test-retest reliability of retrospective self-reports on childhood abuse seems moderate to good, but slightly dependent on the type of abuse. The test-retest reliability was influenced neither by age nor cognition, only reporting of emotional neglect was associated with depression state.

Associations between age and the course of major depressive disorder: a 2-year longitudinal cohort study

Although there is some evidence that older people might have a poorer course of major depressive disorder (MDD) than younger or middle-aged people, and that age-related course differences might affect the optimisation of MDD treatment, large-scale studies with a broad age range, including consistent course assessments, are needed to properly address this issue. Therefore, we aimed to longitudinally examine whether older age was associated with a poorer naturalistic course trajectory of MDD than that of younger ages and to establish which prognostic-clinical, social, and health-factors could explain this potentially poorer course. For this longitudinal cohort study, we used baseline and 2-year follow-up data from the Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands Study of Depression in Older Persons (NESDO) cohorts. People aged between 18 and 88 years, with an MDD diagnosis at baseline, and a valid clinical assessment at 2-year follow-up were included. The primary outcome was the 2-year course of MDD, which was assessed by use of four indicators: having a depression diagnosis (MDD or dysthymia) after 2 years, having a chronic symptom course (depressive symptoms present during 80% or more of the 2-year follow-up period), time to remission, and depression severity change. We used multivariate analyses to examine associations between continuous age and these MDD course indicators. We also examined whether prognostic clinical (eg, comorbid anxiety), social (loneliness and social support), and health (body-mass index, pain, and chronic diseases) factors contributed to the differences in the course of MDD between age groups. Between 2004-2012, baseline and 2-year follow-up data were obtained for 1042 participants from the NESDA and NESDO cohorts, of whom 690 (66%) were women. Older age was significantly associated with a worse 2-year MDD course for all four indicators (MDD diagnosis: odds ratio [OR] 1·08, 95% CI 1·00-1·17; chronic symptom course: OR 1·24, 1·13-1·35; time to remission: hazard ratio [HR] 0·91, 0·87-0·96; and depression severity change: regression coefficient 1·06, p<0·0001; all per 10-year increase). The course of MDD worsened linearly with age, and people aged 70 years or older had the worst outcomes compared with those of the reference group of people aged 18-29 years (MDD diagnosis: OR 2·02, 95% CI 1·18-3·45; chronic symptom course: OR 3·19, 1·74-5·84; time to remission: HR 0·60, 0·44-0·83; and depression severity change: -12·64 [SD 10·85] in those aged 18-29 years and -5·57 [11·14] in those aged 70 years or older). These results were slightly reduced, but remained mostly significant when adjusting for prognostic clinical, social, and health factors. Older age was found to be a consistent and important risk factor for a poorer MDD course, which could not be explained by a range of well established risk factors. Further investigation of potential underlying mechanisms-including the effect of cognitive impairment, for example-is needed to prevent the negative consequences of a long-term MDD burden in older people. Netherlands Organisation for Health Research and Development, Fonds NutsOhra, Stichting tot Steun VCVGZ, NARSAD The Brain and Behaviour Research Fund, and European Union's 7th Framework Programme.

A Six-Year Prospective Study of the Prognosis and Predictors in Patients With Late-Life Depression

To examine the six-year prognosis of patients with late-life depression and to identify prognostic factors of an unfavorable course. The Netherlands Study of Depression in Older Persons (NESDO) is a multisite naturalistic prospective cohort study with six-year follow-up. Three hundred seventy-eight clinically depressed patients (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision criteria) and 132 nondepressed comparisons were included at baseline between 2007 and 2010. Depression was measured by the Inventory of Depressive Symptomatology at 6-month intervals and a diagnostic interview at 2- and 6-year follow-up. Multinomial regression and mixed model analyses were both used to identify depression-related clinical, health, and psychosocial prognostic factors of an unfavorable course. Among depressed patients at baseline, 46.8% were lost to follow-up; 15.9% had an unfavorable course, i.e., chronic or recurrent; 24.6% had partial remission; and 12.7% had full remission at six-year follow-up. The relative risk of mortality in depressed patients was 2.5 (95% confidence interval 1.26-4.81) versus nondepressed comparisons. An unfavorable course of depression was associated with a younger age at depression onset; higher symptom severity of depression, pain, and neuroticism; and loneliness at baseline. Additionally, partial remission was associated with chronic diseases and loneliness at baseline when compared with full remission. The long-term prognosis of late-life depression is poor with regard to mortality and course of depression. Chronic diseases, loneliness, and pain may be used as putative targets for optimizing prevention and treatment strategies for relapse and chronicity.

Development and external validation of a prediction rule for an unfavorable course of late-life depression: A multicenter cohort study

BackgroundGiven the poor prognosis of late-life depression, it is crucial to identify those at risk. Our objective was to construct and validate a prediction rule for an unfavourable course of late-life depression. MethodsFor development and internal validation of the model, we used The Netherlands Study of Depression in Older Persons (NESDO) data. We included participants with a major depressive disorder (MDD) at baseline (n = 270; 60–90 years), assessed with the Composite International Diagnostic Interview (CIDI). For external validation of the model, we used The Netherlands Study of Depression and Anxiety (NESDA) data (n = 197; 50–66 years). The outcome was MDD after 2 years of follow-up, assessed with the CIDI. Candidate predictors concerned sociodemographics, psychopathology, physical symptoms, medication, psychological determinants, and healthcare setting. Model performance was assessed by calculating calibration and discrimination. Results111 subjects (41.1%) had MDD after 2 years of follow-up. Independent predictors of MDD after 2 years were (older) age, (early) onset of depression, severity of depression, anxiety symptoms, comorbid anxiety disorder, fatigue, and loneliness. The final model showed good calibration and reasonable discrimination (AUC of 0.75; 0.70 after external validation). The strongest individual predictor was severity of depression (AUC of 0.69; 0.68 after external validation). LimitationsThe model was developed and validated in The Netherlands, which could affect the cross-country generalizability. ConclusionsBased on rather simple clinical indicators, it is possible to predict the 2-year course of MDD. The prediction rule can be used for monitoring MDD patients and identifying those at risk of an unfavourable outcome.

Apathy in early and late-life depression

BackgroundLate-life depression is thought to differ in clinical presentation from early-life depression. Particularly, late-life depression is considered to be more characterized by apathy than is early-life depression. Lacking convincing evidence, this study examines the presence and associated socio-demographic/clinical characteristics of apathy in older compared to younger depressed persons. MethodsThis cross-sectional study used data from two naturalistic cohort studies, i.e. the Netherlands Study of Depression in Older Persons (NESDO) and the Netherlands Study of Depression and Anxiety (NESDA). These studies included 605 persons (aged 18–93 years) with a major depressive disorder, divided into 217 early-life (< 60 years) and 388 late-life (≥ 60 years) depressed persons. Apathy was considered present if a score of ≥14 on the Apathy Scale. ResultsApathy was strongly associated with age: it was more frequently present in persons with late-life depression (74.5%) than in those with early-life depression (53.5%). Independent of age, the following characteristics were associated with the presence of apathy: male gender, low education, use of benzodiazepines, chronic diseases, and more severe depression. Of all potential risk factors, only former and current smoking was associated with the presence of apathy in older depressed persons but not in younger depressed persons (p-value for age interaction = 0.01). LimitationsNo causal relationships can be drawn due to the cross-sectional design of the study. ConclusionsIn depressed individuals, clinically relevant apathy was more frequently present in older compared to younger persons. Both age groups showed largely the same associated risk factors. Apathy was independently associated with older age, male gender and more severe depression.

Loneliness in older adults is associated with diminished cortisol output

ObjectiveLoneliness in older adults has been associated with increased mortality and health problems. One of the assumed underlying mechanisms is dysregulation of the hypothalamic-pituitary-adrenocortical axis (HPA–axis). The purpose of this study was to investigate whether loneliness in older adults is associated with HPA-axis dysregulation and whether this association differs between depressed and non-depressed persons. MethodsCross-sectional data of 426 lonely and non-lonely older adults in the Netherlands Study of Depression in Older Persons (NESDO) were used. Linear regression analyses and multinominal logistic regression analyses were performed to examine the association between loneliness and morning cortisol, cortisol awakening response, diurnal slope and dexamethasone suppression ratio. In all analyses, confounders were introduced. In order to examine whether the association between loneliness and cortisol measures is different in depressed versus non-depressed persons, an interaction term for loneliness x depression diagnosis was tested. ResultsCortisol output in the first hour after awakening and dexamethasone suppression ratio was lower in lonely participants. There were no significant interactions between loneliness and depression diagnosis in the association with the cortisol measures. ConclusionThis study is the first to investigate the association between the HPA–axis and loneliness in a large group of older adults aged 60–93years. We found lower cortisol output in the first hour after awakening and lower dexamethasone suppression ratio in lonely older depressed and non–depressed adults. Whether diminished cortisol output is the underlying mechanism that leads to health problems in lonely older adults is an interesting object for further study.

The influence of childhood abuse on cortisol levels and the cortisol awakening response in depressed and nondepressed older adults

Objectives: Childhood abuse has been associated with depression in later life. This may be related to hypothalamic-pituitary-adrenal (HPA) axis functioning. Therefore we aimed to examine the impact of childhood abuse and its interaction with depression on cortisol levels in older adults.Methods: Data from 418 participants (mean age 70.8 years) in the Netherlands Study of Depression in Older Persons (NESDO) were used; 187 participants experienced childhood abuse; 309 participants had a diagnosis of depression. Diurnal cortisol levels were determined using six saliva samples from every participant. Multiple regression analyses were performed.Results: Significant negative associations between childhood abuse and morning cortisol levels were found. In nondepressed persons, both psychological and sexual abuse were associated with greater dynamics of the HPA axis in response to awakening.Conclusions: Childhood abuse is associated with lower basal cortisol levels at awakening irrespective of major depressive disorder (MDD). Higher reactivity of the HPA axis during the hour after awakening was found in nondepressed participants only, which might suggest that late-life depression modifies the effect of childhood abuse on the HPA axis. Older adults with a history of childhood abuse may be more negatively affected by stress or stressful events and this is reflected in dysregulation of the HPA axis.

Childhood Abuse and the Two-Year Course of Late-Life Depression

Late-life depression often has a chronic course, with debilitating effects on functioning and quality of life; there is still no consensus on important risk factors explaining this chronicity. Cross-sectional studies have shown that childhood abuse is associated with late-life depression, and in longitudinal studies with chronicity of depression in younger adults. We aim to investigate the impact of childhood abuse on the course of late-life depression. Two-year longitudinal cohort study. Data were derived from the Netherlands Study of Depression in Older Persons (NESDO). 282 participants with a depression diagnosis in the previous 6 months (mean age: 70.6 years), of whom 152 (53.9%) experienced childhood abuse. Presence of childhood abuse (yes/no) and a frequency-based childhood abuse index (CAI) were calculated. Dependent variable was depression diagnosis after 2 years. Multivariable mediation analysis showed an association between childhood abuse and depression diagnosis at follow-up. Depression severity, age at onset, neuroticism, and number of chronic diseases were important mediating variables of this association, which then lost statistical significance. For childhood abuse (yes/no), loneliness was an additional, significant mediator. Depression severity was the main mediating variable, reducing the direct effect by 26.5% to 33.3% depending on the definition of abuse (respectively, 'yes/no" abuse and CAI). More depressive symptoms at baseline, lower age at depression onset, higher levels of neuroticism and loneliness, and more chronic diseases explain a poor course of depression in older adults who reported childhood abuse. When treating late-life depression it is important to detect childhood abuse and consider these mediating variables.

Correlates of sleep disturbances in depressed older persons: the Netherlands study of depression in older persons (NESDO)

ABSTRACTObjectives: Sleep disturbances are common among depressed older persons. To gain insight into sleep disturbances in late-life depression, their occurrence and correlates were assessed. Methods: Baseline data of 294 depressed older persons of the Netherlands Study of Depression in Older persons study were used. A diagnosis of current depression according to the diagnostic and statistical manual of mental disorders-IV (DSM-IV) was assessed with the Composite International Diagnostic Interview. Sleep disturbances were measured with the five-item Women's Health Initiative Insomnia Rating Scale, and considered present with a score of ≥10 points. Results: Sleep disturbances were present in 59.9% of the depressed older persons. Bivariate linear regression analyses showed that presence of sleep disturbances was associated with fewer years of education, use of alcohol, the number of chronic diseases, higher pain intensity scores, use of more benzodiazepines, more anxiety and severity of depressive symptoms. In multivariate analyses, severity of depression appeared to be the only independent correlate.Conclusions: Sleep disturbances are highly prevalent in patients with late-life depression and independently correlated with the severity of depression. Treatment of depression may result in improvement of sleep disturbances, although cognitive behavioral interventions that focus on both depression and sleep disturbances may also be effective.

Age-related variability in the presentation of symptoms of major depressive disorder.

The heterogeneous aetiology of major depressive disorder (MDD) might affect the presentation of depressive symptoms across the lifespan. We examined to what extent a range of mood, cognitive, and somatic/vegetative depressive symptoms were differentially present depending on patient's age. Data came from 1404 participants with current MDD (aged 18-88 years) from two cohort studies: the Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands Study of Depression in Older Persons (NESDO). Associations between age (per 10 years) and 30 depressive symptoms as well as three symptom clusters (mood, cognitive, somatic/vegetative) were assessed using logistic and linear regression analyses. Depression severity was found to be stable with increasing age. Nevertheless, 20 (67%) out of 30 symptoms were associated with age. Most clearly, with ageing there was more often early morning awakening [odds ratio (OR) 1.47, 95% confidence interval (CI) 1.36-1.60], reduced interest in sex (OR 1.42, 95% CI 1.31-1.53), and problems sleeping during the night (OR 1.33, 95% CI 1.24-1.43), whereas symptoms most strongly associated with younger age were interpersonal sensitivity (OR 0.72, 95% CI 0.66-0.79), feeling irritable (OR 0.73, 95% CI 0.67-0.79), and sleeping too much (OR 0.75, 95% CI 0.68-0.83). The sum score of somatic/vegetative symptoms was associated with older age (B = 0.23, p < 0.001), whereas the mood and cognitive sum scores were associated with younger age (B = -0.20, p < 0.001; B = -0.04, p = 0.004). Depression severity was found to be stable across the lifespan, yet depressive symptoms tend to shift with age from being predominantly mood-related to being more somatic/vegetative. Due to the increasing somatic presentation of depression with age, diagnoses may be missed.