Adverse Childhood Experiences and frailty in later life: a prospective population-based cohort study.

BACKGROUND: The deficit accumulation method considers the ageing process underlying frailty as a random accumulation of health deficits. OBJECTIVE: Although Adverse Childhood Experiences (ACE) have consistently been associated with the onset of mental disorders and somatic diseases during adolescence and midlife, it remains unknown whether ACE still exert detrimental health effects in late life. Therefore, we examined cross-sectionally and prospectively the association between ACE and frailty among community-dwelling older people. DESIGN: Based on the health-deficit accumulation method, a Frailty Index was calculated with values ≥0.25 considered as frail. ACE were measured by a validated questionnaire. The cross-sectional association was examined by logistic regression among 2,176 community dwelling participants aged 58-89 years. The prospective association was examined by Cox-regression among 1,427 non-frail participants during a 17-year follow-up. Interactions with age and sex were tested and analyses were adjusted for potential confounders. SETTING: The present study was embedded in the Longitudinal Aging Study Amsterdam. RESULTS: ACE and frailty were positively associated at baseline (OR = 1.88; 95% CI = 1.46-2.42; P = 0.05). Among non-frail participants at baseline (n = 1,427), ACE interacted with age on the prediction of frailty. Stratified analyses showed that a history of ACE only resulted in a higher hazard rate for the incidence of frailty among those aged ≥70 years (HR = 1.28; P = 0.044). CONCLUSION: Even in the oldest-old, ACE still lead to an accelerated rate of the accumulation of health deficits and therefore contribute to the onset of frailty.

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

OBJECTIVES: Polypharmacy 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. METHODS: A 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. RESULTS: Polypharmacy 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). CONCLUSION: Older 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.

Trends in Frailty and Its Association With Mortality: Results From the Longitudinal Aging Study Amsterdam, 1995-2016.

The aim of this study was to investigate trends in frailty and its relationship with mortality among older adults aged 64-84 years across a period of 21 years. We used data from 1995 to 2016 from the Longitudinal Aging Study Amsterdam. A total of 7,742 observations of 2,874 respondents in the same age range (64-84 years) across 6 measurement waves were included. Frailty was measured with a 32-item frailty index, with a cutpoint of ≥0.25 to indicate frailty. The outcome measure was 4-year mortality. Generalized estimating equation analyses showed that among older adults aged 64-84 years the 4-year mortality rate declined between 1995 and 2016, while the prevalence of frailty increased. Across all measurement waves, frailty was associated with 4-year mortality (odds ratio = 2.79, 95% confidence interval: 2.39, 3.26). There was no statistically significant interaction effect between frailty and time on 4-year mortality, indicating a stable association between frailty and mortality. In more recent generations of older adults, frailty prevalence rates were higher, while excess mortality rates of frailty remained the same. This is important information for health policy-makers and clinical practitioners, showing that continued efforts are needed to reduce frailty and its negative health consequences.

A 6-year prospective clinical cohort study on the bidirectional association between frailty and depressive disorder.

INTRODUCTION: Depressive disorder has been conceptualised as a condition of accelerated biological ageing. We operationalised a frailty index (FI) as marker for biological ageing aimed to explore the bidirectional, longitudinal association between frailty and either depressive symptoms or depressive disorder. METHODS: A cohort study with 6-year follow-up including 377 older (≥60 years) outpatients with a DSM-IV-defined depressive disorder and 132 never-depressed controls. Site visits at baseline, 2 and 6-year follow-up were conducted and included the CIDI 2.0 to assess depressive disorder and relevant covariates. Depressive symptom severity and mortality were assessed every 6 months by mail and telephone. A 41-item FI was operationalised and validated against the 6-year morality rate by Cox regression (HRFI  = 1.04 [95% CI: 1.02-1.06]). RESULTS: Cox regression showed that a higher FI was associated with a lower chance of remission among depressed patients (HRFI  = 0.98 [95% CI: 0.97-0.99]). Nonetheless, this latter effect disappeared after adjustment for baseline depressive symptom severity. Linear mixed models showed that the FI increased over time in the whole sample (B[SE] = 0.94 (0.12), p < .001) with a differential impact of depressive symptom severity and depressive disorder. Higher baseline depressive symptom severity was associated with an attenuated and depressive disorder with an accelerated increase of the FI over time. CONCLUSIONS: The sum score of depression rating scales is likely confounded by frailty. Depressive disorder, according to DSM-IV criteria, is associated with accelerated biological ageing. This argues for the development of multidisciplinary geriatric care models incorporating frailty to improve the overall outcome of late-life depression.

Secular trends in the prevalence of major and subthreshold depression among 55-64-year olds over 20 years.

BACKGROUND: Studying secular trends in the exposure to risk and protective factors of depression and whether these trends are associated with secular trends in the prevalence of depression is important to estimate future healthcare demands and to identify targets for prevention. METHODS: Three birth cohorts of 55-64-year olds from the population-based Longitudinal Aging Study Amsterdam were examined using identical methods in 1992 (n = 944), 2002 (n = 964) and 2012 (n = 957). A two-stage screening design was used to identify subthreshold depression (SUBD) and major depressive disorder (MDD). Multinomial logistic regression analyses were used to identify secular trends in depression prevalence and to identify factors from the biopsychosocial domains of functioning that were associated with these trends. RESULTS: Compared with 1992, MDD became more prevalent in 2002 (OR 1.90, 95% CI 1.10-3.28, p = 0.022) and 2012 (OR 1.80, 95% CI 1.03-3.14, p = 0.039). This was largely attributable to an increase in the prevalence of chronic diseases and functional limitations. Socioeconomic and psychosocial improvements, including an increase in labor market participation, social support and mastery, hampered MDD rates to rise more and were also associated with a 32% decline of SUBD-rates in 2012 as compared with 2002 (OR 0.68, 95% CI 0.48-0.96, p = 0.03). CONCLUSIONS: Among late middle-aged adults, there is a substantial net increase of MDD, which is associated with deteriorating physical health. If morbidity and disability continue to increase, a further expansion of MDD rates may be expected. Improving socioeconomic and psychosocial conditions may benefit public health, as these factors were protective against a higher prevalence of both MDD and SUBD.

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

OBJECTIVES: To examine the six-year prognosis of patients with late-life depression and to identify prognostic factors of an unfavorable course. DESIGN AND SETTING: The Netherlands Study of Depression in Older Persons (NESDO) is a multisite naturalistic prospective cohort study with six-year follow-up. PARTICIPANTS: 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. MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: 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.

The effectiveness of off-label dopamine stimulating agents in depressive disorder: A systematic review and meta-analysis.

The chronicity of depressive disorders is a major problem. Dopamine stimulating agents (DSA) are suggested to hold a promising potential in depression management, particularly in older adults, in whom dopamine deficiency due to aging may be an underlying cause. More evidence is needed to support these drugs in the management of depression. Therefore, we conducted a systematic literature review and meta-analysis. Data was extracted from eighteen randomized-controlled-trials and eight open-label-studies. Additional meta-regression-analyses were performed to examine superiority of monotherapy versus augmentation, and to rule out a putative age effect. DSA were found to reduce depressive symptoms (SMD=-0.26, 95%CI[-0.43;-0.10]). Heterogeneity was high and a significant Egger's test indicated publication bias. Adjustment for missing studies, using trim-and-fill-methodology, reduced the effect size (SMD=-0.17, 95%CI[-0.39;0.05]), which lost statistical significance. Removing the outlier study from the analysis, the effect size remained marginally small, but was statistically-significant (SMD=-0.17, 95%CI[-0.31;-0.02]). Neither augmentation nor monotherapy was superior. No age effect was found. It can be concluded that off-label DSA are overall effective in reducing depressive symptoms. However, the evidence is weak, regarding the publication bias, and modest-to-weak treatment effects. Well-designed high-quality trials are highly needed, before dopamine stimulating agents can be adequately positioned in future depression treatment protocols.

The Frail Depressed Patient: A Narrative Review on Treatment Challenges.

Although the public importance of frailty is widely acknowledged by the World Health Organization, physical frailty is still largely neglected in geriatric mental health care. Firstly in this narrative review, we summarize the knowledge on the epidemiology of the association between depression and frailty, whereafter implications for treatment will be discussed. Even though frailty and depression have overlapping diagnostic criteria, epidemiological studies provide evidence for distinct constructs which are bidirectionally associated. Among depressed patients, frailty has predictive validity being associated with increased mortality rates and an exponentially higher fall risk due to antidepressants. Nonetheless, guidelines on the treatment of depression neither consider frailty for risk stratification nor for treatment selection. We argue that frailty assessment enables clinicians to better target the pharmacological and psychological treatment of depression as well as the need for interventions targeting primarily frailty, for instance, lifestyle interventions and reduction of polypharmacy. Applying a frailty informed framework of depression treatment studies included in a meta-analysis reveals that the benefit-harm ratio of antidepressants given to frail depressed patients can be questioned. Nonetheless, frail-depressed patients should not withhold antidepressants as formal studies are not available yet, but potential adverse effects should be closely monitored. Dopaminergic antidepressants might be preferable when slowness is a prominent clinical feature. Psychotherapy is an important alternative for pharmacological treatment, especially psychotherapeutic approaches within the movement of positive psychology, but this approach needs further study. Finally, geriatric rehabilitation, including physical exercise and nutritional advice, should also be considered. In this regard, targeting ageing-related abnormalities underlying frailty that may also be involved in late-life depression such as low-grade inflammation might be a promising target for future studies. The lack of treatment studies precludes firm recommendations, but more awareness for frailty in mental health care will open a plethora of alternative treatment options to be considered.

Frailty and affective disorders throughout adult life: A 5-year follow-up of the Lifelines Cohort Study.

BACKGROUND: Frailty is an important concept for risk stratification in clinical practice, but it is hardly acknowledged at all in mental healthcare settings. This paper aims to assess the impact of frailty on the course of depression and anxiety, and the impact of these affective disorders on the course of frailty. METHODS: Lifelines, a prospective population-based cohort study, evaluated 167,729 people living in the northern Netherlands. Frailty was based on the deficit accumulation model, which resulted in a 60-item frailty index (FI) at baseline and a 35-item FI at baseline and 5-year follow-up. Current depressive and anxiety disorders were assessed with the Mini International Neuropsychiatric Interview according to DSM-IV criteria. Bidirectional associations between frailty and affective disorders were investigated using separate multivariable regression analyses in younger (<60 years) and older adults (≥60 years). RESULTS: The FI was associated with the onset of a depressive disorder (younger adults: odds ratio [OR] = 1.12; 95% confidence interval [CI] 1.11-1.13; older adults: OR = 1.13; 95% CI 1.09-1.16) as well as any anxiety disorder (younger adults: OR = 1.10; 95% CI 1.09-1.10; older adults: OR = 1.07; 95% CI 1.04-1.09). The other way around, depressive disorder and anxiety disorders were associated with an accelerated increase of frailty over time (depressive disorder: younger adults: beta [ß] = 0.03, p < 0.001; older adults: ß = 0.04, p < 0.001; and any anxiety disorder: younger adults: ß = 0.02, p < 0.001; older adults: ß = 0.01, p < 0.142), although the effect of anxiety disorders was less equivocal among older adults. CONCLUSIONS: Affective disorders are reciprocally related to frailty. Results with respect to the impact of anxiety disorders on frailty suggest most impact at lower levels of frailty. Our results might imply that interventions to slow biological aging should be broadened towards younger and middle-aged people as well as non-frail older patients. To develop targeted treatment, future clinical and epidemiologic studies on the underlying pathways of this bidirectional association are needed.

Secular trends in excess mortality of late-life depression.

BACKGROUND: Late-life depression is associated with premature mortality, however, little is known whether excess mortality rates of depression have changed over time. This study aims to identify and explain secular trends in excess mortality of major depressive disorder (MDD) and subthreshold depression (SUBD). METHODS: Cohort-sequential-longitudinal study of 4084 community-dwelling older adults in the Netherlands based on data from the Longitudinal Aging Study Amsterdam (LASA). Six measurement cycles were included from 1992/93 until 2008/09, each linked to the overall 5-year mortality, covering a 16-year time span. MDD and SUBD were identified using a two-stage screening procedure with the Center for Epidemiological Studies Depression Scale and the Diagnostic Interview Schedule. Age and sex were covariates. Education, health and lifestyle factors, and use of antidepressants were included as putative explanatory factors. Generalized Estimating Equations was used to investigate the association between the interaction 'Depression × Time' and 5-year mortality, and to find explanatory factors for the trend. RESULTS: A downward trend in excess mortality of MDD was found (OR = .92, 95%-CI:.85-.99, P = .04), adjusted for age and sex, which could not be explained by education, health and lifestyle factors, nor antidepressants use. Sex differences in the trend were not found (P = .77). No trend in excess mortality of SUBD was found (OR = 1.01, 95%-CI: .97-1.04, P = .65). LIMITATIONS: The findings do not imply a similar trend for other countries. CONCLUSIONS: The results indicate a favorable development in excess mortality of community-dwelling older adults with MDD, while those with SUBD do not show a clear trend in excess mortality.