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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: People with dementia and severe challenging behavior in the Netherlands can be temporarily admitted to highly specialized units when their behavior is not manageable in regular dementia special care units (DSCUs). With scarce evidence available for the treatment of these patients, treatment in these units is in a pioneering phase. To gain more insight into these units, this study investigated organizational characteristics, i.e. admission and discharge characteristics, staffing, the physical environment, and the management of severe challenging behavior., Methods: Three data collection methods were used: 1) a digital questionnaire to be completed by the unit manager, 2) an interview with the physician responsible for medical care and often another practitioner, and 3) an observation of the physical environment for which the OAZIS-dementia questionnaire was used. Descriptive analysis was used for quantitative data and thematic analysis for qualitative data, after which data was interpreted together. Thirteen units participated, with their sizes ranging from 10 to 28 places., Results: Patients were mainly admitted from regular DSCUs, home or mental health care, and discharged to regular DSCUs. A multidisciplinary team comprising at least an elderly care physician or geriatrician, psychologist, and nursing staff member and other therapists as needed provided the treatment. Nursing staff hours per patient considerably differed among units. Nursing staff played a central role in the treatment. Competences such as reflectiveness on one's own behavior, and being able to cope with stressful situations were described as relevant for nursing staff. Investing in a stable nursing staff team was described as important. The units varied in whether their work-up was more intuitive or methodological. In the diagnostic phase, observation together with an extensive analysis of the patient's biography was essential. The units used a broad variety of interventions, and all paid attention to sensory stimuli. In the observation of the physical environment, the safety scored well and domesticity relatively low., Conclusion: Highly specialized units show strong heterogeneity in organizational characteristics and management, which can be understood in the light of the pioneering phase. Despite this, similarities were found in nursing staff roles, frequent multidisciplinary evaluation, and attention to sensory stimuli., (© 2024. The Author(s).)

Background: Cognitive behavioural therapy (CBT) is the most researched psychological therapy for anxiety disorders in adults, and known to be effective in this population. However, it remains unclear whether these results apply to older adults, as most studies include participants between 18 and 55 years of age. This systematic review aims to provide a comprehensive and up-to-date synthesis of the available evidence on CBT and third wave approaches for older adults with anxiety and related disorders., Objectives: To assess the effects of Cognitive Behavioural Therapy (CT, BT, CBT and third-wave CBT interventions) on severity of anxiety symptoms compared with minimal management (not providing therapy) for anxiety and related disorders in older adults, aged 55 years or over. To assess the effects of CBT and related therapies on severity of anxiety symptoms compared with other psychological therapies for anxiety and related disorders in older adults, aged 55 years or over., Search Methods: We searched the Cochrane Common Mental Disorders Controlled studies Register (CCMDCTR), CENTRAL, Ovid MEDLINE, Ovid Embase and Ovid PsycINFO to 21 July 2022. These searches were updated on 2 February 2024. We also searched the international studies registries, including Clinicalstudies.gov and the WHO International Clinical Trials Registry Platform (ICTRP), to identify additional ongoing and unpublished studies. These sources were manually searched for studies up to 12 February 2024., Selection Criteria: We included randomised controlled trials (RCTs) in older adults (≥ 55 years) with an anxiety disorder, or a related disorder, including obsessive compulsive disorder (OCD), acute stress disorder and post-traumatic stress disorder (PTSD), that compared CBT to either minimal management or an active (non-CBT) psychological therapy. Eligible studies had to have an anxiety-related outcome., Data Collection and Analysis: Several authors independently screened all titles identified by the searches. All full texts were screened for eligibility according to our prespecified selection criteria. Data were extracted and the risk of bias was assessed using the Cochrane tool for RCTs. The certainty of evidence was evaluated using GRADE. Meta-analyses were performed for outcomes with quantitative data from more than one study., Main Results: We included 21 RCTs on 1234 older people allocated to either CBT or control conditions. Ten studies focused on generalised anxiety disorder; others mostly included a mix of clinical diagnoses. Nineteen studies focused on the comparison between CBT and minimal management. Key issues relating to risk of bias were lack of blinding of participants and personnel, and participants dropping out of studies, potentially due to treatment preference and allocation. CBT may result in a small-to-moderate reduction of anxiety post-treatment (SMD -0.51, 95% CI -0.66 to -0.36, low-certainty evidence). However, compared to this benefit with CBT immediately after treatment, at three to six months post-treatment, there was little to no difference between CBT and minimal management (SMD -0.29, 95% CI -0.59 to 0.01, low-certainty evidence). CBT may have little or no effect on clinical recovery/ improvement post-treatment compared to minimal management, but the evidence is very uncertain (RR 1.56, 95% CI 1.20 to 2.03, very low-certainty evidence). Results indicate that five people would need to receive treatment for one additional person to benefit (NNTB = 5). Compared to minimal management, CBT may result in a reduction of comorbid depression symptoms post-treatment (SMD -0.57, 95% CI -0.74 to -0.40, low-certainty evidence). There was no difference in dropout rates post-treatment, although the certainty of the evidence was low (RR 1.19, 95% CI 0.80 to 1.78). Two studies reported adverse events, both of which related to medication in the control groups (very low-certainty evidence, no quantitative estimate). Only two studies compared CBT to other psychological therapies, both of which only included participants with post-traumatic stress disorder. Low-certainty evidence showed no difference in anxiety severity post-treatment and at four to six months post-treatment, symptoms of depression post-treatment, and dropout rates post-treatment. Other outcomes and time points are reported in the results section of the manuscript., Authors' Conclusions: CBT may be more effective than minimal management in reducing anxiety and symptoms of worry and depression post-treatment in older adults with anxiety disorders. The evidence is less certain longer-term and for other outcomes including clinical recovery/improvement. There is not enough evidence to determine whether CBT is more effective than alternative psychological therapies for anxiety in older adults., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

The absence of treatment studies for obsessive compulsive disorder (OCD) in older adults and the fact that OCD typically starts at a young age and often follows a chronic, fluctuating course quickly leads to therapeutic nihilism for older adults with OCD. In this case report, we present a 72-year-old man with OCD symptoms from the age of 35, who has only been treated with medication and psychotherapy for a recurrent depressive disorder. After a short, intensive exposure and response prevention treatment (four days in two weeks), the OCD symptoms and the depressive symptoms were fully in remission and all medications (venlafaxine, olanzapine, depakine) were discontinued. Treatment gains were maintained with persistent remission until 18 months follow up. This case report shows that a comorbid depressive disorder may lead to undertreatment of OCD. It also shows that long standing OCD can be successfully treated in older adults.

The term depression is overused as an umbrella term for a variety of conditions, including depressed mood and various psychiatric disorders. According to psychiatric diagnostic criteria, depressive disorders impact nearly all aspects of human life and are a leading cause of disability worldwide. The widespread assumption that different types of depression lie on a continuum of severity has stimulated important research on subthreshold depression in later life. This view assumes that depressed mood is a precursor of a depressive disorder. The present narrative review argues why in later life depressed mood might either (i) lie on a continuum with depressive disorders among people vulnerable for a depressive disorder or (ii) be an ageing-related epiphenomenon of underlying physical illnesses in people who are resilient to depressive disorders ('discontinuity hypothesis'). Three arguments are discussed. First, the course of depressed mood and depressive disorders differs across the life span. Second, screening instruments for depression have low predictive value for depressive disorders in later life. Third, a dose-response relationship has not been consistently found across different types of depression and detrimental health outcomes. Using the umbrella term depression may partly explain why pharmacological treatment is less effective with increasing age, and negative health-related outcomes might be overestimated. The discontinuity hypothesis may prevent pharmacological overtreatment of milder subtypes of depression and may stimulate comprehensive multidisciplinary assessment as well as the development of separate treatment algorithms for depressed mood and depressive disorders., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Background: Recovery in mental health care comprises more than symptomatic improvement, but preliminary evidence suggests that only collaborative care may improve functioning of depressed older adults. This study therefore evaluates the effectiveness of behavioural activation (BA) on functional limitations in depressed older adults in primary care., Methods: This study uses data from a multicentre cluster randomised controlled trial in which 59 primary care centres (PCCs) were randomised to BA and treatment as usual (TAU), and 161 consenting older (≥65 years) adults with clinically relevant symptoms of depression participated. Interventions were an eight-week individual BA programme by a mental health nurse (MHN) and unrestricted TAU. The outcome was self-reported functional limitations (WHODAS 2.0) at post-treatment (9 weeks) and at 12-month follow-up., Results: At the end of treatment, the BA participants reported significantly fewer functional limitations than TAU participants (WHODAS 2.0 difference -3.62, p  = 0.01, between-group effect size = 0.39; 95% CI = 0.09-0.69). This medium effect size decreases during follow-up resulting in a small and non-significant effect at the 12-month follow-up (WHODAS 2.0 difference = -2.22, p  = 0.14, between-group effect size = 0.24; 95% CI = -0.08-0.56). MoCA score moderated these results, indicating that the between-group differences were merely driven by those with no cognitive impairment., Conclusions: Compared to TAU, BA leads to a faster improvement of functional limitations in depressed older adults with no signs of cognitive decline. Replication of these findings in confirmatory research is needed.

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.)

Euthanasia was first legalized in the Netherlands and Belgium in 2001 and 2002, respectively. Currently they are among the few countries that also allow euthanasia on the basis of dementia, which is still considered controversial, both from a scientific and societal perspective. To date, euthanasia in dementia constitutes a small proportion of all Dutch and Belgian euthanasia cases. However, instances are rising due to a growing awareness among the general public about the possibilities of a self-chosen end-of-life and the willingness among medical professionals to perform euthanasia in individuals diagnosed with dementia. In both countries euthanasia is allowed under strict conditions in patients with dementia and decisional capacity regarding euthanasia, while in the Netherlands an advance euthanasia directive can also replace an oral request for euthanasia in those with late-stage dementia. Judging euthanasia requests from patients with dementia is complex and the assessment of the due care criteria (especially those related to decisional capacity and unbearable suffering) requires caution and great care. In this narrative review, we reflect on the legal regulation, clinical guidelines and societal debate regarding euthanasia in dementia in the Netherlands and Belgium. By discussing the 20 years of experience with the ethical dilemmas and controversial aspects surrounding this delicate topic, we hope to inform the preparation or implementation of new legislation on euthanasia in dementia in other countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marijnissen, Chambaere and Oude Voshaar.)

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).)

Background: Comorbidity between depression and cognitive impairment is common in older adults, increases the disease burden disproportionally, and leads to diagnostic uncertainty. Insight into individual daily associations between affect and cognitive performance may help in personalizing diagnosis and treatment decisions. Our objective was to get insight into the daily associations between affect and cognitive performance within individual older adults., Methods: In this single-subject study seven older adults with both depression and cognitive impairment filled in electronic diaries daily for 62-93 consecutive days evaluating positive affect (PA), negative affect (NA), working memory (WM) and visual learning (VL). Time-series analyses using vector autoregressive modelling, Granger causality tests and cumulative orthogonalized impulse response function analyses were performed for each individual separately., Results: In one patient higher NA was associated with better WM the next day. For another patient days with higher NA and lower PA were days with worse WM. For a third patient better VL was associated with lower NA and higher PA the next day. No associations were found for four patients., Conclusions: These results highlight heterogeneity in the daily associations between affect and cognitive performance and stress the relevance of single-subject studies. These studies may be an important step towards personalized diagnosis and treatment in old age psychiatry., (© 2022. The Author(s).)

Background: The prevalence of geriatric syndromes, frailty and multimorbidity increases in older age, with a negative impact on health outcomes. Little is known on these problems in older adults with psychiatric disorders., Aim: To evaluate the prevalence of geriatric syndromes and multimorbidity in older adults with psychiatric disorders and their impact on treatment outcomes., Method: We conducted a pilot study and a case-control study on older adults with medically insufficiently explained symptoms, a prospective cohort study in older adults, acutely admitted to psychiatric wards and a systematic review to evaluate whether geriatric syndromes were considered in RCTs on depression treatment., Results: Unexplained symptoms were often accompanied by frailty, multimorbidity and psychiatric disorders. Older adults who were acutely admitted to psychiatric wards had a high level of multimorbidity, about half of them were frail, and a third undernourished. Frailty and multimorbidity were independent predictors for not being discharged to their own home. Frailty also strongly predicted the 5-year mortality rate. Geriatric syndromes were hardly considered in study design or as secondary outcome in treatment studies on depression in older adults., Conclusion: Overall, geriatric problems are highly prevalent among older adults with psychiatric disorders and have a relevant prognostic impact. The complexity of older psychiatric patients is probably best addressed by interdisciplinary, integrated diagnostic and treatment trajectories.

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: Increasing age as well as borderline personality pathology are associated with a lower level of health-related quality of life (HR-QoL). Our objective was to investigate whether the presence of borderline personality traits modifies the association between age and HR-QoL in the general population., Methods: Cross-sectional data from 5,303 respondents (aged 21-72 years) of the Netherlands Mental Health Survey and Incidence Study-2 were analyzed. Borderline personality traits were assessed with the International Personality Disorder Examination questionnaire. Mental and physical HR-QoL were measured with the Medical Outcomes Study Short Form Health Survey. Multiple linear regression analysis was used to examine the association of borderline personality traits, age and their interaction on mental as well as physical HR-QoL, adjusted for demographic variables as well as somatic and mental disorders., Results: A total of 1,520 (28.7%) respondents reported one or more borderline personality traits of which 58 (1.1%) reported five or more indicative of a borderline personality disorder. A higher age was associated with lower physical HR-QoL. This negative association became significantly stronger in the presence of borderline personality traits. The association between increasing age and mental HR-QoL was positive in the absence of borderline personality traits and negative in the presence of borderline personality traits., Conclusion: Borderline personality traits negatively interfere with the association between age and HR-QoL irrespective of somatic and mental disorders. Attention of clinicians and researchers for subthreshold borderline personality pathology is needed in middle-aged and older persons.

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.

Background: To investigate whether an exercise intervention using the VIVIFRAIL© protocol has benefits for inflammatory and functional parameters in different frailty status., Methods/design: This is a randomized clinical trial in an outpatient geriatrics clinic including older adults ≥60 years. For each frailty state (frail, pre-frail and robust), forty-four volunteers will be randomly allocated to the control group (n = 22) and the intervention group (n = 22) for 12 weeks. In the control group, participants will have meetings of health education while those in the intervention group will be part of a multicomponent exercise program (VIVIFRAIL©) performed five times a week (two times supervised and 3 times of home-based exercises). The primary outcome is a change in the inflammatory profile (a reduction in inflammatory interleukins [IL-6, TNF- α, IL1beta, IL-17, IL-22, CXCL-8, and IL-27] or an increase in anti-inflammatory mediators [IL-10, IL1RA, IL-4]). Secondary outcomes are change in physical performance using the Short Physical Performance Battery, handgrip strength, fatigue, gait speed, dual-task gait speed, depressive symptoms, FRAIL-BR and SARC-F scores, and quality of life at the 12-week period of intervention and after 3 months of follow-up., Discussion: We expect a reduction in inflammatory interleukins or an increase in anti-inflammatory mediators in those who performed the VIVIFRAIL© protocol. The results of the study will imply in a better knowledge about the effect of a low-cost intervention that could be easily replicated in outpatient care for the prevention and treatment of frailty, especially regarding the inflammatory and anti-inflammatory pathways involved in its pathophysiology., Trial Registration: Brazilian Registry of Clinical Trials (RBR-9n5jbw; 01/24/2020). Registred January 2020. http://www.ensaiosclinicos.gov.br/rg/RBR-9n5jbw/ .

Objectives: Significant weight loss and/or loss of appetite is a criterion of a depressive episode. While malnutrition is associated with many adverse health outcomes, the impact of malnutrition in late-life depression has hardly been examined. The present study aims to (1) evaluate the prevalence of malnutrition in depressed older inpatients, and (2) whether and which indices of malnutrition predict adverse health outcomes in late-life depression., Design: A prospective study at 6 months follow-up., Setting: A University-based psychiatric hospital., Participants: 105 older adults (psychiatric inpatients suffering from unipolar MDD)., Measurements: Participants were evaluated according the Mini Nutritional Assessment (MNA) and anthropometric measures to assess their nutritional status. Multiple regression analyses were used to evaluate the association between the MNA score as well as anthropometric measures with either falls or rehospitalization for any reason., Results: Based on the MNA score, 78 (74.3%) patients were at risk of malnutrition and 13 (12.4%) actually presented malnutrition. Malnutrition was associated with a higher age, frailty, lower body mass index, and smaller calf circumference. During follow-up, 21 (20%) patients fell, 27 (25.7%) were rehospitalized, and 3 died (2.9%). The MNA score was associated with adverse health outcomes, but a low calf circumference predicted falling (OR 4.93 [95% CI: 1.42-17.2], p=.012) and a higher calf circumference rehospitalization (OR 1.17 [95% CI: 1.01-1.35], p=.032)., Conclusion: Malnutrition is prevalent in older depressed inpatients. In contrast to subjective proxies for malnutrition, which are common in depression, only objective measures of malnutrition predict adverse health outcomes such as falls and rehospitalization., Competing Interests: No potential conflict of interest was reported by the authors.

Objectives: The aim of the present study was to investigate whether late-life depression (LLD) is associated with incident frailty over time., Design: Prospective cohort study, one-year follow-up., Setting: Geriatric outpatient clinic, Southwestern of Brazil., Participants: 181 follow-up participants aged 60 years or over., Measurements: Depressive disorders were classified as Major Depressive disorder (MDD) or Subthreshold Depression (STD) according to DSM-5 criteria. Depressive symptoms were assessed with validated versions of 15-item Geriatric Depression Scale (GDS-15) and 9-item Patient Health Questionnaire (PHQ-9). We performed binary logistic regressions to estimate the odds ratio (OR) for frailty in LLD adjusting for multiple confounders. Participants who were frail at baseline were excluded from the analyses according to measures of frailty (FRAIL questionnaire and 36-item Frailty Index, FI-36). We also estimated the risk ratio or relative risk (RR) and the risk difference (RD) for incident frailty., Results: We observed a 2 to 4-fold increased risk for incident frailty among participants with LLD. The presence of a depressive disorder was significantly associated with the onset of frailty (adjusted OR for FRAIL and FI-36: 3.07 [95% CI = 1.03 - 9.17] and 3.76 [95% CI = 1.09 - 12.97], respectively. Notably, the risk for frailty due to LLD was significantly higher with the FI-36 compared to the FRAIL (RR: 3.03 versus 2.23). RD was of 17.3% and 12.7% with the FRAIL and the FI-36, respectively., Conclusion: Our data support the association between LLD and incident frailty over one year among geriatric outpatients, reinforcing longitudinal evidence from population-based studies., Competing Interests: No potential conflict of interest was reported by the authors.

Background: To explore the mutual relationship between multimorbidity, mental illness and frailty, we have set-up the Multimorbidity and Mental health Cohort Study in FRAILty and Aging (MiMiCS-FRAIL) cohort. At the population level, multimorbidity, frailty and late-life depression are associated with similar adverse outcomes (i.e. falls, disability, hospitalization, death), share the same risk factors, and partly overlap in their clinical presentation. Moreover, these three variables may share a common underlying pathophysiological mechanism like immune-metabolic dysregulation. The overall objectives of MiMiCS-FRAIL are 1) to explore (determinants of) the cross-sectional and longitudinal relationship between multimorbidity, depression, and frailty among non-demented geriatric outpatients; 2) to evaluate molecular levels of senoinflammation as a broad pathophysiological process underlying these conditions; and 3) to examine adverse outcomes of multimorbidity, frailty and depression and their interconnectedness., Methods: MiMiCS-FRAIL is an ongoing observational cohort study of geriatric outpatients in Brazil, with an extensive baseline assessment and yearly follow-up assessments. Each assessment includes a comprehensive geriatric assessment to identify multimorbidity and geriatric syndromes, a structured psychiatric diagnostic interview and administration of the PHQ-9 to measure depression, and several frailty measures (FRAIL, Physical Phenotype criteria, 36-item Frailty Index). Fasten blood samples are collected at baseline to assess circulating inflammatory and anti-inflammatory cytokines, leukocytes' subpopulations, and to perform immune-metabolic-paired miRome analyses. The primary outcome is death and secondary outcomes are the number of falls, hospital admissions, functional ability, well-being, and dementia. Assuming a 5-year mortality rate between 25 and 40% and a hazard rate varying between 1.6 and 2.3 for the primary determinants require a sample size between 136 and 711 patients to detect a statistically significant effect with a power of 80% (beta = 0.2), an alpha of 5% (0.05), and an R 2 between the predictor (death) and all covariates of 0.20. Local ethical board approved this study., Discussion: Frailty might be hypothesized as a final common pathway by which many clinical conditions like depression and chronic diseases (multimorbidity) culminate in many adverse effects. The MiMiCS-FRAIL cohort will help us to understand the interrelationship between these variables, from a clinical perspective as well as their underlying molecular signature.

Introduction: Descendants of patients with dementia have a higher risk to develop dementia. This study aims to investigate the uptake and effectiveness of an online tailor-made lifestyle programme for dementia risk reduction (DRR) among middle-aged descendants of people with recently diagnosed late-onset dementia., Methods and Analysis: Demin is a cluster randomised controlled trial, aiming to include 21 memory clinics of which 13 will be randomly allocated to the passive (poster and flyer in a waiting room) and 8 to the active recruitment strategy (additional personal invitation by members of the team of the memory clinic). We aim to recruit 378 participants (40-60 years) with a parent who is recently diagnosed with Alzheimer's disease or vascular dementia at one of the participating memory clinics. All participants receive a dementia risk assessment (online questionnaire, physical examination and blood sample) and subsequently an online tailor-made lifestyle advice regarding protective (Mediterranean diet, low/moderate alcohol consumption and high cognitive activity) and risk factors (physical inactivity, smoking, loneliness, cardiovascular diseases (CVD), hypertension, high cholesterol, diabetes, obesity, renal dysfunction and depression) for dementia. The primary outcome is the difference in uptake between the two recruitment strategies. Secondary outcomes are change(s) in (1) the Lifestyle for Brain Health score, (2) individual health behaviours, (3) health beliefs and attitudes towards DRR and (4) compliance to the tailor-made lifestyle advice. Outcomes will be measured at 3, 6, 9 and 12 months after baseline. The effectiveness of this online tailor-made lifestyle programme will be evaluated by comparing Demin participants to a matched control group (lifelines cohort)., Ethics and Dissemination: This study has been approved by the Dutch Ministry of Health, Welfare and Sport according to the Population Screening Act. All participants have to give online informed consent using SMS-tan (transaction authentication number delivered via text message). Findings will be disseminated through peer-reviewed journals and (inter)national conferences., Trial Registration Number: NTR7434., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: Empirical studies on the clinical characteristics of older persons with medically unexplained symptoms are limited to uncontrolled pilot studies. Therefore, we aim to examine the psychiatric characteristics of older patients with medically unexplained symptoms (MUS) compared to older patients with medically explained symptoms (MES), also across healthcare settings., Methods: A case-control study including 118 older patients with MUS and 154 older patients with MES. To include patients with various developmental and severity stages, patients with MUS were recruited in the community (n = 12), primary care (n = 77), and specialized healthcare (n = 29). Psychopathology was assessed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria (Mini-International Neuropsychiatric Interview) and by dimensional measures (e.g., psychological distress, hypochondriasis, and depressive symptoms)., Results: A total of 69/118 (58.5%) patients with MUS met the criteria for a somatoform disorder according to DSM-IV-TR criteria, with the highest proportion among patients recruited in specialized healthcare settings (p = 0.008). Patients with MUS had a higher level of psychological distress and hypochondriasis compared to patients with MES. Although psychiatric disorders (beyond somatoform disorders) were more frequently found among patients with MUS compared to patients with MES (42.4 vs. 24.8%, p = 0.008), this difference disappeared when adjusted for age, sex, and level of education (odds ratio = 1.7 [95% confidence interval: 1.0-3.0], p = 0.070)., Conclusions: Although psychological distress is significantly higher among older patients with MUS compared to those with MES, psychiatric comorbidity rates hardly differ between both patient groups. Therefore, treatment of MUS in later life should primarily focus on reducing psychological distress, irrespective of the healthcare setting patients are treated in.

Objectives: Frailty is characterized by a functioning decline in multiple systems accompanied by an increase in individual's vulnerability to stressors. It appears to be higher in low and middle-income countries compared with high-income ones. This study aimed to evaluate the prevalence of frailty in non-institutionalized Brazilian older adults., Design: a systematic review and meta-analysis study., Setting: Cross-sectional and prospective data from Brazil., Participants: non-institutionalized adults aged 60 and older., Methods: Electronic searches were performed in PubMed/MEDLINE, LILACS, SCOPUS and Web of Science, considering the studies published between March 2001 and July 2018, using a combination of the following terms and correlates: "elder" AND "frail" AND "prevalence" AND "Brazil". Two independent reviewers selected studies according to the inclusion criteria. Disagreements were resolved by a third reviewer (title/abstract) and by consensus. Studies with samples ≥221 subjects were considered for meta-analysis., Results: 28 studies were included, while 18 had the data meta-analyzed. The majority of studies (61%) included older adults only from the Southeastern region. The number of subjects ranged from 53 to 5,532 individuals (N = 17,604) and the average age ranged from 65.6 to 85.5 years. The overall prevalence of frailty was 24%. When considering the different assessment methods, the prevalence was lower for frailty phenotype (16%) compared with other criteria (40%). Regarding sex, the prevalence of frailty was similar for women (28%) and men (25%). The prevalence of frailty was higher in older adults recruited from health care services (30%) compared to community ones (22%)., Conclusion: In Brazil, the overall prevalence of frailty in non-institutionalized older adults is higher than observed from more developed countries. However, it may vary according to the assessment methods and settings., Competing Interests: The authors declare no conflict of interest.

Background: Affective disorders, encompassing depressive-, anxiety-, and somatic symptom disorders, are the most prevalent mental disorders in later life. Treatment protocols and guidelines largely rely on evidence from RCTs conducted in younger age samples and ignore comorbidity between these disorders. Moreover, studies in geriatric psychiatry are often limited to the "younger old" and rarely include the most frail. Therefore, the effectiveness of treatment in routine clinical care for older patients and impact of ageing characteristics is largely unknown., Objective: The primary aim of the Routine Outcome Monitoring for Geriatric Psychiatry & Science (ROM-GPS) - project is to examine the impact of ageing characteristics on the effectiveness of treatment for affective disorders in specialised geriatric mental health care., Methods: ROM-GPS is a two-stage, multicentre project. In stage one, all patients aged ≥60 years referred to participating outpatient clinics for specialised geriatric mental health care will be routinely screened with a semi-structured psychiatric interview, the Mini International Neuropsychiatric Interview and self-report symptom severity scales assessing depression, generalized anxiety, hypochondria, and alcohol use. Patients with a unipolar depressive, anxiety or somatic symptom disorder will be asked informed consent to participate in a second (research) stage to be extensively phenotyped at baseline and closely monitored during their first year of treatment with remission at one-year follow-up as the primary outcome parameter. In addition to a large test battery of potential confounders, specific attention is paid to cognitive functioning (including computerized tests with the Cogstate test battery as well as paper and pencil tests) and physical functioning (including multimorbidity, polypharmacy, and different frailty indicators). The study is designed as an ongoing project, enabling minor adaptations once a year (change of instruments)., Discussion: Although effectiveness studies using observational data can easily be biased, potential selection bias can be quantified and potentially corrected (e.g. by propensity scoring). Knowledge of age-related determinants of treatment effectiveness, may stimulate the development of new interventions. Moreover, studying late-life depressive, anxiety and somatic symptom disorders jointly enables data-driven studies for more optimal classification of these disorders in later life., Trial Registration: Dutch Trial Register: NL6704 ( www.trialregister.nl ). Retrospectively registered on 2017-12-05.

Anxiety sensitivity is associated with the onset of panic attacks, anxiety, and other common mental disorders. Anxiety sensitivity is usually seen as a relative stable trait. However, previous studies were inconclusive regarding the longitudinal stability of anxiety sensitivity and differed in study designs and outcomes. The current study examines the stability of anxiety sensitivity over time and its longitudinal associations with severity of anxiety symptoms. Participants from the Netherlands Study of Depression and Anxiety with and without an anxiety, depressive, or comorbid anxiety-depressive disorder diagnosis were included (N = 2052). Stability in anxiety sensitivity over two year follow-up and the longitudinal association between the change in anxiety sensitivity and change in severity of anxiety symptoms were tested. Results indicated that two-year stability of anxiety sensitivity was high (r = 0.72), yet this test-retest estimate leaves room for changes in anxiety sensitivity in some individuals as well. Change in anxiety sensitivity was positively associated with change in severity of anxiety symptoms (B = 0.64 in univariable analysis and B = 0.52 in multivariable analysis). The longitudinal association of anxiety sensitivity with severity of anxiety symptoms indicates that targeting anxiety sensitivity may be of additional benefit in clinical practice.

Background: Depression is common among older adults and is typically treated with antidepressants., Objective: To determine the non-adherence rates to antidepressants among older adults in primary care, based on non-initiation, suboptimal implementation or non-persistence., Methods: We selected all patients aged ≥60 years and diagnosed with depression in 2012, from the Netherlands Institute for Health Services Research (NIVEL) Primary Care Database. Non-initiation was defined as no dispensing within 14 days of the first prescription; suboptimal implementation, as fewer than 80% of the days covered by dispensed dosages; and non-persistence, as discontinuation within 294 days after first dispense. First, we determined the antidepressant non-initiation, suboptimal implementation and non-persistence rates. Second, we examined whether comorbidity and chronic drug use were associated with non-adherence by mixed-effects logistic regression (non-initiation or suboptimal implementation as dependent variables) and a clustered Cox regression (time to non-persistence)., Results: Non-initiation, suboptimal implementation and non-persistence rates were 13.5%, 15.2% and 37.1%, respectively. As the number of chronically used drugs increased, the odds of suboptimal implementation (odds ratio, 0.89; 95% confidence interval, 0.83-0.95) and of non-persistence (hazard ratio, 0.87; 95% confidence interval, 0.82-0.92) reduced., Conclusions: Non-adherence to antidepressants is high among older patients with depression in primary care settings. Adherence is better when patients are accustomed to taking larger numbers of prescribed drugs, but this only provides partial explanation of the variance. GPs should be aware of the high rates of non-adherence. Emphasizing the importance of adhering to the optimal length of antidepressant therapy might be prudent first steps to improving adherence.

Background: Several types of psychotherapy have been proven successful in the treatment of personality disorders in younger age groups, however studies among older patients are lacking. We developed a group schema-focused therapy (SFT) enriched with psychomotor therapy (PMT) for older adults with cluster B and/or C personality disorders. This paper describes the design of a randomized controlled trial (RCT). We will evaluate the (cost-)effectiveness of this therapy protocol in specialized mental health care. We hypothesize that our treatment program is cost-effective and superior to treatment as usual (TAU) in reducing psychological distress and improving quality of life in older adults treated to specialized mental healthcare., Methods: A multicenter RCT with a one-year follow-up comparing group schema-focused therapy enriched with psychomotor therapy (group SFT + PMT) and TAU for adults aged 60 years and older who suffer from either a cluster B and/or C personality disorder. The primary outcome is general psychological distress measured with the 53-item Brief Symptom Inventory. Secondary outcomes are the Schema Mode Inventory (118-item version) and the Young Schema Questionnaire. Cost-effectiveness analysis will be performed from a societal perspective with the EuroQol five dimensions questionnaire and structured cost-interviews., Discussion: This study will add to the knowledge of psychotherapy in later life. The study specifically contributes to the evidence on (cost-) effectiveness of group SFT enriched with PMT adapted to the needs of for older adults with cluster b and/or c personality., Trial Registration: Netherlands Trial Register NTR 6621 . Registered on 20 August 2017.

Aims: Poor recovery from depressive disorder has been shown to be related to low perceived social support and loneliness, but not to social network size or frequency of social interactions. Some studies suggest that the significance of social relationships for depression course may be greater in younger than in older patients, and may differ between men and women. None of the studies examined to what extent the different aspects of social relationships have unique or overlapping predictive values for depression course. It is the aim of the present study to examine the differential predictive values of social network characteristics, social support and loneliness for the course of depressive disorder, and to test whether these predictive associations are modified by gender or age., Methods: Two naturalistic cohort studies with the same design and overlapping instruments were combined to obtain a study sample of 1474 patients with a major depressive disorder, of whom 1181 (80.1%) could be studied over a 2-year period. Social relational variables were assessed at baseline. Two aspects of depression course were studied: remission at 2-year follow-up and change in depression severity over the follow-up period. By means of logistic regression and random coefficient analysis, the individual and combined predictive values of the different social relational variables for depression course were studied, controlling for potential confounders and checking for effect modification by age (below 60 v. 60 years or older) and gender., Results: Multiple aspects of the social network, social support and loneliness were related to depression course, independent of potential confounders - including depression severity - but when combined, their predictive values were found to overlap to a large extent. Only the social network characteristic of living in a larger household, the social support characteristic of few negative experiences with the support from a partner or close friend, and limited feelings of loneliness proved to have unique predictive value for a favourable course of depression. Little evidence was found for effect modification by gender or age., Conclusions: If depressed persons experience difficulties in their social relationships, this may impede their recovery. Special attention for interpersonal problems, social isolation and feelings of loneliness seems warranted in depression treatment and relapse prevention. It will be of great interest to test whether social relational interventions can contribute to better recovery and relapse prevention of depressive disorder.

Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons─including 2165 depressed and 1058 non-depressed persons. In both cohorts, separately as well as combined, there was a significant non-linear association between the risk of lifetime depression and HTT CAG repeat size in which both relatively short and relatively large alleles were associated with an increased risk of depression (β = -0.292 and β = 0.006 for the linear and the quadratic term, respectively; both P < 0.01 after adjustment for the effects of sex, age, and education level). The odds of lifetime depression were lowest in persons with a HTT CAG repeat size of 21 (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average odds in the total cohort. In conclusion, lifetime depression risk was higher with both relatively short and relatively large HTT CAG repeat sizes in the normal range. Our study provides important proof-of-principle that repeat polymorphisms can act as hitherto unappreciated but complex genetic modifiers of depression.

Background and Objectives: In the proposed symptom network approach to psychopathology, psychiatric disorders are assumed to result from the (causal) interplay between symptoms. By implementing this approach we explored whether individual feedback on symptom dynamics complements current categorical classification and treatment. The aim of this proof-of-principle case-study was to explore the feasibility, acceptability and usability of this transdiagnostic approach., Methods: A female patient, aged 67, suffering from treatment resistant anxious and depressive symptoms was treated in our tertiary outpatient clinic for old age psychiatry. She participated in ecological momentary assessments (EMA), which involved intensive repeated measurements of mood and context-related items during two weeks. Visualizations of the interplay between the items were provided by network graphs and were discussed with the patient., Results: Network graphs were discussed with the patient. For example, it was hypothesized and discussed with the patient that feeling relaxed increased physical activity, causing physical discomfort in the following hours. Physical discomfort caused stress as its symptoms resembled her feared somatic anxiety symptoms. This increased the patient's insight that stress, expressed as somatic symptoms, played a central role in her panic disorder. This started a dialogue on how to cope with stress caused by somatic (anxiety) symptoms and provided a rationale for the patient to start an interoceptive exposure intervention she had repeatedly refused before., Limitations: The observed symptom dynamics may not be generalizable to any other random two weeks., Conclusions: Personalized diagnosis of psychopathology incorporating complex symptom dynamics is feasible and a promising addition to current categorical diagnostic systems and could guide intervention selection. This merits further exploration., (© Person-Oriented Research.)

Background: Late-life depression is most often treated in primary care, and it usually coincides with chronic somatic diseases. Given that antidepressants contribute to polypharmacy in these patients, and potentially to interactions with other drugs, non-pharmacological treatments are essential. In this systematic review and meta-analysis, we aimed to present an overview of the non-pharmacological treatments available in primary care for late-life depression., Method: The databases of PubMed, PsychINFO, and the Cochrane Central Register of Controlled Trials were systematically searched in January 2017 with combinations of MeSH-terms and free text words for "general practice," "older adults," "depression," and "non-pharmacological treatment". All studies with empirical data concerning adults aged 60 years or older were included, and the results were stratified by primary care, and community setting. We narratively reviewed the results and performed a meta-analysis on cognitive behavioral therapy in the primary care setting., Results: We included 11 studies conducted in primary care, which covered the following five treatment modalities: cognitive behavioral therapy, exercise, problem-solving therapy, behavioral activation, and bright-light therapy. Overall, the meta-analysis showed a small effect for cognitive behavioral therapy, with one study also showing that bright-light therapy was effective. Another 18 studies, which evaluated potential non-pharmacological interventions in the community suitable for implementation, indicated that bibliotherapy, life-review, problem-solving therapy, and cognitive behavioral therapy were effective at short-term follow-up., Discussion: We conclude that the effects of several treatments are promising, but need to be replicated before they can be implemented more widely in primary care. Although more treatment modalities were effective in a community setting, more research is needed to investigate whether these treatments are also applicable in primary care., Trial Registration: PROSPERO CRD42016038442.

Background: depression is associated with worse executive function, but underlying mechanisms might differ by age., Aims: to investigate whether vascular disease burden affects the association between depression and executive dysfunction differentially by age., Method: among 83,613 participants of Lifelines (population-based cohort study), linear regression analyses were applied to examine the association between executive function (Ruff Figural Fluency test, dependent variable) and depression according to DSM-IV criteria (Mini International Neuropsychiatric Interview, independent variable)., Results: adjusted for demographic characteristics, major depressive disorder was associated with a lower level of executive function in both younger and older adults. Minor depressive disorder was only associated with worse executive function in younger adults. Adding vascular disease burden to the final model with major depressive disorder, reduced this strength of this association by 5.9% in younger and 5.0% in older adults., Conclusions: major depression was associated with worse executive function across the lifespan, but minor depression only in younger adults. The impact of vascular burden on the association did not differ between younger and older adults. Therefore, vascular risk reduction is important in both age groups., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com)

Depression is one of the most prevalent and debilitating psychiatric disorders worldwide. Recently, we showed that both relatively short and relatively long cytosine-adenine-guanine (CAG) repeats in the huntingtin gene (HTT) are associated with an increased risk of lifetime depression. However, to what extent the variations in CAG repeat length in the other eight polyglutamine disease-associated genes (PDAGs) are associated with depression is still unknown. We determined the CAG repeat sizes of ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, ATN1 and AR in two well-characterized Dutch cohorts-the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons-including 2165 depressed and 1058 non-depressed individuals-aged 18-93 years. The association between PDAG CAG repeat size and the risk for depression was assessed via binary logistic regression. We found that the odds ratio (OR) for lifetime depression was significantly higher for individuals with >10, compared with subjects with ≤10, CAG repeats in both ATXN7 alleles (OR=1.90, confidence interval (CI) 1.26-2.85). For TBP we found a similar association: A CAG repeat length exceeding the median in both alleles was associated with an increased risk for lifetime depression (OR=1.33, CI 1.00-1.76). In conclusion, we observed that carriers of either ATXN7 or TBP alleles with relatively large CAG repeat sizes in both alleles had a substantially increased risk of lifetime depression. Our findings provide critical evidence for the notion that repeat polymorphisms can act as complex genetic modifiers of depression.

Background: The Ruff Figural Fluency Test (RFFT; a pencil and paper test) and the CogState (a computerized cognitive test battery) are well-validated and suitable tests to evaluate cognitive functioning in large observational studies at the population level. The LifeLines Cohort Study includes the RFFT as baseline measurement and incorporated the CogState as replacement for the RFFT at follow-up. It is unknown how these two tests relate to each other. Therefore, the aim of this study is to examine the correlation between the RFFT and the CogState and the impact of demographic characteristics on this association., Methods: A subcohort of the LifeLines Cohort Study, a large population based cohort study, participated in this study. Correlations between the RFFT and six subtasks of the CogState were examined. Subgroup analyses were performed to investigate the influence of age, education, and gender on the results. With sensitivity analyses we investigated the influence of computer experience and (physical) impairments., Results: A total of 509 participants (mean age (SD): 53 years (14.6); range 18-87 years) participated in this study. All correlations between the RFFT and the CogState were statistically significant (except for the correlation between the RFFT error ratio and the CogState One Back Task), ranging from -0.39 to 0.28. Stratifying the analyses for age, education, and gender did not substantially affect our conclusions. Sensitivity analyses showed no substantial influence of level of computer experience or (physical) impairments., Conclusions: Correlations found in the present study were only weak to moderate, indicating that cognitive functioning measured by the RFFT does not measure the same components of cognitive functioning as six subtasks of the CogState. Computerized testing such as the CogState may be very well suited for large cohort studies to assess cognitive functioning in the general population and to identify cognitive changes as early as possible, as it is a less time- and labor intensive tool.

Background: Research in younger patients with medically unexplained symptoms (MUS) has shown impairments in social functioning, such as loneliness and a reduced quality of the patient-doctor relationship. As far as we know, no studies have been performed on social functioning in older MUS patients; self-reported care needs of older MUS patients remain unknown., Objective: To explore social characteristics and care needs of older persons with chronic MUS, when compared to older persons with chronic medically explained symptoms (MES)., Methods: Patient characteristics of 107 older persons (>60 years) with chronic MUS were compared to 150 older persons with chronic MES in a case-control design. Participants were recruited via advertisements, general practices and a specialized clinic. All participants completed questionnaires on social functioning; the Camberwell Assessment of Need for the Elderly was used to draw up care needs. Linear regression analyses were performed to explore the association between social characteristics and group (MUS/MES), adjusted for demographic and physical determinants. Multiple chi-square tests were performed to detect between-group differences regarding care needs., Results: After adjustments, older MUS patients were slightly but significantly lonelier, reported a somewhat lower quality of their patient-doctor relationship, but reported equal social support levels when compared to MES patients. MUS patients more often reported unmet care needs regarding health and information provision about their health status., Conclusion: Only small differences in social functioning were found between older MUS and MES patients. Possibly, training future doctors in giving acceptable explanations for the patient's complaints could improve the unmet care need of information provision in older MUS patients., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although poor social relationships are assumed to contribute to cognitive decline, meta-analytic approaches have not been applied. Individual study results are mixed and difficult to interpret due to heterogeneity in measures of social relationships. We conducted a systematic review and meta-analysis to investigate the relation between poor social relationships and cognitive decline., Methods: MEDLINE, Embase and PsycINFO were searched for longitudinal cohort studies examining various aspects of social relationships and cognitive decline in the general population. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random effects meta-analysis. Sources of heterogeneity were explored and likelihood of publication bias was assessed. We stratified analyses according to three aspects of social relationships: structural, functional and a combination of these., Results: We identified 43 articles. Poor social relationships predicted cognitive decline; for structural (19 studies): pooled OR: 1.08 (95% CI: 1.05-1.11); functional (8 studies): pooled OR: 1.15 (95% CI: 1.00-1.32); and combined measures (7 studies): pooled OR: 1.12 (95% CI: 1.01-1.24). Meta-regression and subgroup analyses showed that the heterogeneity could be explained by the type of social relationship measurement and methodological quality of included studies., Conclusions: Despite heterogeneity in study design and measures, our meta-analyses show that multiple aspects of social relationships are associated with cognitive decline. As evidence for publication bias was found, the association might be overestimated and should therefore be interpreted with caution. Future studies are needed to better define the mechanisms underlying these associations. Potential causality of this prognostic association should be examined in future randomized controlled studies., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Major depressive disorder is a heterogeneous disorder, mostly diagnosed on the basis of symptomatic criteria alone. It would be of great help when specific biomarkers for various subtypes and symptom clusters of depression become available to assist in diagnosis and subtyping of depression, and to enable monitoring and prognosis of treatment response. However, currently known biomarkers do not reach sufficient sensitivity and specificity, and often the relation to underlying pathophysiology is unclear. In this review, we evaluate various biomarker approaches in terms of scientific merit and clinical applicability. Finally, we discuss how combined biomarker approaches in both preclinical and clinical studies can help to make the connection between the clinical manifestations of depression and the underlying pathophysiology.

A low plasma 25-OH vitamin D3 level is a universal risk factor for a wide range of diseases and has also been implicated in late-life depression. It is currently unknown whether the biologically active form of vitamin D, that is, 1,25-(OH)2 vitamin D3, is also decreased in late-life depression, or whether vitamin D levels correlate with specific depression characteristics. We determined plasma 25-OH vitamin D3, 1,25-(OH)2 vitamin D3 and parathormone levels in 355 depressed older persons and 124 non-depressed comparison subjects (age 60 years). Psychopathology was established with the Composite International Diagnostic Interview 2.1, together with potential confounders and depression characteristics (severity, symptom profile, age of onset, recurrence, chronicity and antidepressant drug use). Adjusted for confounders, depressed patients had significantly lower levels of 25-OH vitamin D33 (Cohen's d =0.28 (95% confidence interval: 0.07-0.49), P=0.033) as well as 1,25-(OH)2 vitamin D3 (Cohen's d =0.48 (95% confidence interval: 0.27-0.70), P<0.001) than comparison subjects. Of all depression characteristics tested, only the use of tricyclic antidepressants (TCAs) was significantly correlated with lower 1,25-(OH)2 vitamin D3 levels (Cohen's d =0.86 (95% confidence interval: 0.53-1.19), P<0.001), but not its often measured precursor 25-OH vitamin D3. As vitamin D levels were significantly lower after adjustment for confounders, vitamin D might have an aetiological role in late-life depression. Differences between depressed and non-depressed subjects were largest for the biologically active form of vitamin D. The differential impact of TCAs on 25-OH vitamin D3 and 1,25-(OH)2 vitamin D3 levels suggests modulation of 1-α-hydroxylase and/or 24-hydroxylase, which may in turn have clinical implications for biological ageing mechanisms in late-life depression.

Background: Although it is generally agreed that personality disorders are an important topic in old-age psychiatry, DSM-5 has paid relatively little attention to older persons affected with this severe mental disorder., Aim: To look closely and carefully at several aspects of the way in which DSM-5 defines personality disorders relating to older persons., Method: We make a critical evaluation of the description of personality disorders given in DSM-5., Results: First of all, we question whether the phrase 'personality change due to another medical condition' should really be included in the dsm-5 chapter of personality disorders because a personality change actually has the features of a persistent conduct disorder. Secondly, we argue that in a future revised version of dsm-5 personality disorders affecting older persons should be referred to specifically as 'late-onset' personality disorders. Thirdly, we stress that the research programme relating to the dimensional dsm-5 model of personality disorders should involve a larger number of older persons. In addition, more research is needed with regard to the use, wording and validity of the phrase 'personality change due to a medical condition'. Those responsible for the revision of the DSM-5 should ensure that the concept 'late-onset personality disorders' is incorporated in the text., Conclusion: The description of personality disorders in DSM-5 is confusing. This is probably due to the transitional period between the old categorical (dsm-iv) system and the newly proposed dimensional approach to personality disorders in DSM-5, an approach that needs further investigation. However, this intervening period could be a good opportunity for doing further research into personality disorders in older adults.

Background: Tolerance towards the effects of benzodiazepines is observed in various animal and human studies. Therefore, it is assumed that patients who use benzodiazepines for a longer period of time need to increase their dose over time to experience the same effect., Objective: To observe whether long-term benzodiazepine users increase their dose over time., Methods: From the Dutch National Information Network of Family Practices, a group of long-term benzodiazepine users was identified. This group was divided into an incident long-term benzodiazepine users group (N = 113) and a prevalent long-term benzodiazepine users group (N = 992). Long-term use of benzodiazepines was defined as usage for at least 6 months. The main outcome was a change in prescribed dose from baseline until 24 months after baseline. Linear regression analysis was performed to evaluate dose change., Results: Neither incident long-term benzodiazepine users nor prevalent long-term benzodiazepine users were prescribed increasing dosages during follow-up., Conclusion: There is no increase in prescribed dose among long-term users, as might be expected due to the development of tolerance to the effects of benzodiazepines.

Due to the increased use of cerebral imaging with higher sensitivity, the old-age psychiatrist is more likely to find unexpected lesions. We report on a 73-year-old man with schizoaffective disorder and increasing cognitive deterioration. When given a diagnostic MRI cerebrum a pituitary incidentaloma was found. An overview of the literature shows a high prevalence of pituitary incidentalomas. Complications are generally rare, but one should be alert. The old-age psychiatrist should take the lead in the assessment and interpretation of such imaging results. The relevant skills for this task should be developed in the field of old-age psychiatry during the residency training in psychiatry.

Benzodiazepines are frequently prescribed for a longer period of time for anxiety disorders and insomnia in spite of the many guidelines to prescribe these drugs only short-term. These guidelines are based on the risk-benefit balance between long-term effectiveness and side effects like addiction, anterograde amnesia, and increased risk on falling (resulting in hip fractures), traffic accidents and even mortality. Also low-dose benzodiazepine use can lead to benzodiazepine dependence. Although initially most attention has been paid to the physical withdrawal syndrome, psychological aspects of benzodiazepine dependence have received more and more attention in the past decades. Recently, a relationship between the brain-reward system, involved in addiction, and benzodiazepine use, was demonstrated. When long-term benzodiazepine use is recognised as problematic by both physician and patient, different treatment modalities are available to support patients in achieving abstinence. One of every four patients is able to stop by themselves with the aid of a minimal intervention providing psychoeducation and encouragement. Two out of three long-term uses are able to stop their usage with the aid of systematic tapering protocols guided by a physician or psychologist. In case of an underlying insomnia or anxiety disorder, cognitive-behavioural therapy should be added to the tapering protocol. In contrast to the general opinion, advanced old age has no negative impact on the treatment response.

Background: In the March edition of this journal a group of professors criticised the methods adopted by the SBG (Benchmark foundation of the Dutch Mental Health Services). The critical comments relate to the alleged objectives ('pay-for-performance' in the Dutch Mental Health Services) and the methods involving confounding, bias and the use of insufficiently sensitive instruments., Aim: To provide more detailed information about the SBG and the role of the scientific council (WR) and about the social context within which rom and benchmarking are developing, and to give our views on the methodological criticisms., Method: We elucidate the methods of the SBG and the role of the WR and we clarify the ways in which ROM and benchmarking are currently being used., Results: We recognise that there are methodological problems. The wr too warns against jumping to conclusions on the basis of data whose validity is still under discussion. The Dutch Mental Health Services have practically no experience of rom and benchmarking. The Dutch Mental Health Services need to gain more experience in this field. On the other hand, it is true that rom data and comparisons between institutions can lead to improvements in the standard of care, provided these procedures are carried out carefully. In the SGB methods the aforementioned problems have been removed, at least partially. The SBG is concerned not only with symptom reduction but also with the functioning of the individual and with his or her quality of life., Conclusion: The WR believes that the Dutch Mental Health Services should operate a scientifically validated benchmark system. Sofar, there has been hardly any research into whether benchmark data really say anything about quality and/or whether comparisons between institutions are valid. A national ROM-system is needed. Current initiatives are creating ways in which these matters can be investigated, preferably in conjunction with scientists and professionals.

Background: Frailty can be regarded as a condition in which the reserve capacity of various physical systems has sunk to a critical low, at which point minor disturbances can develop into serious health problems., Aim: To review the various operationalisations of the concept of frailty and describe the relationship between frailty and psychopathology., Method: We searched the literature up to October 2010 using PubMed, PsycINFO and CINAHL., Results: We found 35 operationalisations of the concept of frailty; 4 single measurements as a proxy for frailty (e.g. muscle strength), 18 syndrome diagnoses which can be subdivided into single (n = 5) and multiple syndrome diagnoses (n = 13) and 13 dimensional operationalisations for which measurement instruments were used. Only 6 studies reported the relationship between frailty and psychopathology. The studies revealed an association between depression and psychopathology. An important finding was the association between depression and frailty, but the direction of the association is unknown., Conclusion: No consensus has been reached regarding the operationalisation of the concept of frailty. For the purpose of gerontopsychiatric research we recommend the inclusion of a syndrome diagnosis based on physical criteria (physical frailty) because this should make it possible to unravel the relationship between psychopathology and underlying ageing mechanisms.