Search

Ivan Aprahamian,1,2 Marcus K Borges,3 Denise J C Hanssen,2 Hans W Jeuring,2 Richard C Oude Voshaar2 1Group of Investigation on Multimorbidity and Mental Health in Aging (GIMMA), Geriatrics Division, Department of Internal Medicine, Jundiaí Medical School, Jundiaí, Brazil; 2University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, the Netherlands; 3Federal University of Paraná, Department of Psychiatry, Curitiba, BrazilCorrespondence: Ivan Aprahamian, Group of Investigation on Multimorbidity and Mental Health in Aging (GIMMA), Division of Geriatrics, Department of Internal Medicine, Jundiaí Medical School, Jundiaí, Brazil, Email ivan.aprahamian@gmail.comAbstract: 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.Keywords: frailty, depression, depressive disorder

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A 47-year-old highly educated man without psychiatric history was referred for psychiatric evaluation because of persistent subjective cognitive decline after repeated and extensive diagnostic evaluation in an outpatient memory clinic. The patient developed increasing preoccupation and anxiety with memory complaints and concerns, despite repetitive negative findings from clinical investigations. This clinical case is coined as ‘neurocognitive hypochondria’, a syndrome interfacing with cogniform and illness anxiety disorders, in which obsessions and concerns about progression of unexplained memory deficits are indicated for specialized treatment. This case study provides more insight into differential diagnosis, classification according to the current DSM-5 criteria and discussion on potential treatment approaches.

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., Competing Interests: Declaration of Competing Interest none., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

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 [β] = 0.03, p < 0.001; older adults: β = 0.04, p < 0.001; and any anxiety disorder: younger adults: β = 0.02, p < 0.001; older adults: β = 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., (© 2022 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

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., (© 2022 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: Child abuse is a major global burden with an enduring negative impact on mental and physical health. A history of child abuse is consistently associated with worse cognitive performance among adults; data in older age groups are inconclusive. Since affective symptoms and cognitive functioning are interrelated among older persons, a synergistic effect can be assumed in patients with affective symptoms who also have suffered from child abuse. This study examines the association between a history of child abuse and cognitive performance in such patients., Methods: Cross-sectional data were collected from the 'Routine Outcome Monitoring for Geriatric Psychiatry & Science' project, including 179 older adults (age 60-88 years) with either a unipolar depressive, any anxiety, or somatic symptom disorder referred to specialized geriatric mental health care. A history of physical, sexual, and psychological abuse, and emotional neglect was assessed with a structured interview. Cognitive functioning was measured with three paper and pencils tests (10-words verbal memory test, Stroop Colour-Word test, Digit Span) and four tests from the computerized Cogstate Test Battery (Detection Test, Identification Test, One Card Learning Test, One Back Test). The association between a history of child abuse and cognitive performance was examined by multiple linear regression analyses adjusted for covariates., Results: Principal component analyses of nine cognitive parameters revealed four cognitive domains, i.e., visual-verbal memory, psychomotor speed, working memory and interference control. A history of child abuse was not associated with any of these cognitive domains. However, when looking at the specific types of child abuse separately, a history of physical abuse and emotional neglect were associated with poorer interference control. A history of physical abuse was additionally associated with better visual-verbal memory., Conclusions: The association between a history of child abuse and cognitive performance differs between the different types of abuse. A history of physical abuse might particularly be a key determinant of cognitive performance in older adults with a depressive, anxiety, or somatic symptom disorder. Future studies on the impact of these disorders on the onset of dementia should take child abuse into account., Trial Registration: ROM-GPS is registered at the Dutch Trial Register ( NL6704 at www.trialregister.nl )., (© 2022. The Author(s).)

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 (HR FI  = 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 (HR FI  = 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., (© 2021 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Objectives: Frailty marks an increased risk for adverse health outcomes. Since childhood trauma is associated with the onset of physical and mental health diseases during the lifespan, we examined the link between childhood trauma and multidimensional frailty., Method: A cross-sectional study embedded in a clinical cohort study (ROM-GPS) of older (≥60 years) patients (n=182) with a unipolar depressive-, anxiety- and/or somatic symptom disorder according to DSM-criteria referred to specialized geriatric mental health care. Frailty was assessed with the Tilburg Frailty Indicator (TFI), comprising a physical, psychological, and social dimension. Physical, sexual and psychological abuse and emotional neglect before the age of 16 years was measured with a structured interview., Results: Of 182 patients, 103 (56.6%) had experienced any childhood trauma and 154 (84.6%) were frail (TFI sum score ≥5). Linear regression analyses, adjusted for lifestyle, psychological and physical-health factors, showed that the presence of any type of childhood trauma was not associated with the TFI sum score, however when considered separately, physical abuse was (ß=0.16, p=.037). Regarding the specific frailty dimensions, any childhood trauma was associated with social frailty (ß=0.18, p=.019), with emotional neglect as main contributor., Conclusion: These findings demonstrate a complex link between different types of childhood trauma and multidimensional frailty among older psychiatric patients. Regarding the three dimensions of frailty, social frailty seems most affected by childhood trauma. This may have been underestimated until now and should receive more attention in clinical care and future research., (Copyright © 2021. Published by Elsevier B.V.)

Background: To examine the mortality risk of current and life-time depressive as well as anxiety disorders, whether this risk is moderated by sex or age, and whether this risk can be explained by lifestyle and/or somatic health status., Methods: A cohort study (Lifelines) including 141,377 participants (18-93 years) which were followed-up regarding mortality for 8.6 years (range 3.0-13.7). Baseline depressive and anxiety disorders according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria were assessed with the Mini International Neuropsychiatric Interview and lifetime diagnoses by self-report. All-cause mortality was retrieved from Statistics Netherlands. Cox-regression was applied to calculate proportional hazard ratios, adjusted for lifestyle (physical activity, alcohol use, smoking, and body mass index) and somatic health status (multimorbidity and frailty) in different models., Results: The mortality rate of depressive and anxiety disorders was conditional upon age but not on sex. Only in people below 60 years, current depressive and anxiety disorders were associated with mortality. Only depressive disorder and panic disorder independently predicted mortality when all mental disorders were included simultaneously in one overall model (hazard ratio [HR] = 2.18 [95% confidence intervals (CI): 1.56-3.05], p < 0.001 and HR = 2.39 [95% CI: 1.15-4.98], p = 0.020). Life-time depressive and anxiety disorders, however, were independent of each other associated with mortality. Associations hardly changed when adjusted for lifestyle characteristics but decreased substantially when adjusted for somatic health status (in particular physical frailty)., Conclusions: In particular, depressive disorder is associated with excess mortality in people below 60 years, independent of their lifestyle. This effect seems partly explained by multimorbidity and frailty, which suggest that chronic disease management of depression-associated somatic morbidity needs to be (further) improved.

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: The frailty index (FI) is a well-recognized measurement for risk stratification in older people. Among middle-aged and older people, we examined the prospective association between the FI and mortality as well as its course over time in relation to multimorbidity and specific disease clusters., Methods: A frailty index (FI) was constructed based on either 64 (baseline only) or 35 health deficits (baseline and follow-up) among people aged ≥ 40 years who participated in LifeLines, a prospective population-based cohort living in the Northern Netherlands. Among 92,640 participants, multivariable Cox proportional hazard models were fitted to study the hazard ratio (HR) of the FI at baseline, as well as for 10 chronic disease clusters for all-cause mortality over a 10-year follow-up. Among 55,426 participants, linear regression analyses were applied to study the impact of multimorbidity and of specific chronic disease clusters (independent variables) on the change of frailty over a 5-year follow-up, adjusted for demographic and lifestyle characteristics., Results: The FI predicted mortality independent of multimorbidity and specific disease clusters, with the highest impact in people with either endocrine, lung, or heart diseases. Adjusted for demographic and lifestyle characteristics, all chronic disease clusters remained independently associated with an accelerated increase of frailty over time., Conclusions: Frailty may be seen as a final common pathway for premature death due to chronic diseases. Our results suggest that initiating frailty prevention at middle age, when the first chronic diseases emerge, might be relevant from a public health perspective.

Aims: Studying birth-cohort differences in depression incidence and their explanatory factors may provide insight into the aetiology of depression and could help to optimise prevention strategies to reduce the worldwide burden of depression., Methods: Data were used from the Longitudinal Aging Study Amsterdam, a nationally representative study among community dwelling older adults in the Netherlands. Cohort differences in depression incidence over a 10-year-period (score ⩾16 on the Center for Epidemiologic Studies Depression scale) were tested using a cohort-sequential-longitudinal-design, comparing two identically measured cohorts of non-depressed 55-64-year-olds, born 10-years apart. Baseline measurements took place in 1992/93 (early cohort, n = 794), and 2002/03 (recent cohort, n = 771). As indicated by the dynamic equilibrium model of depression, potential explanatory factors were distinguished in risk and protective factors., Results: The incidence rates for depression in the early and recent cohort were 1.91 (95% confidence interval (CI) 1.59-2.27) and 1.60 (95% CI 1.31-1.94) per 100 person-years, respectively. A 29% risk reduction in depression incidence was observed in the recent cohort (HRcohort: 0.71, 95% CI 0.54-0.92, p = 0.011), as compared with the early cohort, even though average levels of risk factors such as chronic disease and functional limitations had increased. This reduction was primarily explained by increased levels of education, mastery and labour market participation., Conclusions: These findings suggest that favourable developments of protective factors have counterbalanced unfavourable effects of risk factors on the incidence of depression, resulting in a net reduction of depression incidence among young-old adults. However, maintaining a good physical health must be a priority to further decrease depression rates.

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., (Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

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.

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Subthreshold depression (SUBD) in later life is common and important as prodromal state and prominent risk factor in the development of major depressive disorder (MDD). Indicated prevention can reduce the incidence of MDD among people with SUBD substantially, but needs to be targeted to those that are truly at risk of developing MDD., Method: N = 341 eligible participants with SUBD were included from the first (1992/1993), second (1995/1996) and third (1998/1999) cycle from the Longitudinal Aging Study Amsterdam (LASA) by using a two-stage screening design. LASA is an ongoing prospective cohort study in The Netherlands among the older population (55-85 years). At baseline (1992/1993) N = 3107 participants were interviewed and follow-up cycles were conducted every 3 years until 2008/2009, resulting in maximal 17 years of observational period. The proportion of people that developed MDD, remained SUBD, or recovered from SUBD was measured and Cox proportional regression analyses were performed to investigate 29 putative predictors of MDD and recovery from SUBD., Results: N = 153 (44.9%) recovered from SUBD, N = 138 (40.5%) remained chronically SUBD, and N = 50 (14.7%) developed MDD (incidence rate 15.1/1000 person-years). Women, high neuroticism, more chronic diseases, high body mass index, smoking and less social support predicted conversion to MDD. Men, low neuroticism and absence of pain predicted recovery from SUBD., Conclusions: Although older people with SUBD are clearly at risk of developing MDD, the majority did not, even after a long and thorough follow-up. Given the risk factors that were uncovered, targeting and prevention of MDD in those at very high risk is feasible.