Search

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.)

Introduction: Depression in older adults is associated with decreased quality of life and increased utilization of healthcare services. Behavioral activation (BA) is an effective treatment for late-life depression, but the cost-effectiveness compared to treatment as usual (TAU) is unknown., Methods: An economic evaluation was performed alongside a cluster randomized controlled multicenter trial including 161 older adults (≥65 years) with moderate to severe depressive symptoms (PHQ-9 ≥ 10). Outcome measures were depression (response on the QIDS-SR), quality-adjusted life-years (QALYs) and societal costs. Missing data were imputed using multiple imputation. Cost and effect differences were estimated using bivariate linear regression models, and statistical uncertainty was estimated with bootstrapping. Cost-effectiveness acceptability curves showed the probability of cost-effectiveness at different ceiling ratios., Results: Societal costs were statistically non-significantly lower in BA compared to TAU (mean difference (MD) -€485, 95 % CI -3861 to 2792). There were no significant differences in response on the QIDS-SR (MD 0.085, 95 % CI -0.015 to 0.19), and QALYs (MD 0.026, 95 % CI -0.0037 to 0.055). On average, BA was dominant over TAU (i.e., more effective and less expensive), although the probability of dominance was only 0.60 from the societal perspective and 0.85 from the health care perspective for both QIDS-SR response and QALYs., Discussion: Although the results suggest that BA is dominant over TAU, there was considerable uncertainty surrounding the cost-effectiveness estimates which precludes firm conclusions., Competing Interests: Declaration of competing interest GJH occasionally receives honoraria for lectures at symposia. On a yearly basis it is never more than €1000. DE is Chief investigator for UK NIHR funded multimorbidity in older adults program of research. A program in a similar clinical area looking at BA in people 65 and over with 2 or more health problems and depression. HvM was supported by the National Institute of Health Research (NIHR) Applied Health Collaboration Kent, Surrey, Sussex. The views expressed are those of the author(s) and not necessarily the NHS, the NIHR or the Department of Health and Social Care. All other authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Late Life Depression (LLD) is associated with increased mortality rates, but it remains unclear which depressed patients are at increased risk. This study examined the mortality risk of previously identified subgroups of depressed older patients based on age-related clinical features (the presence of physical and cognitive frailty)., Methods: A six-year follow-up of a clinical cohort study including 375 depressed older patients and 132 non-depressed persons (NESDO). Depressed patients were diagnosed with the Composite International Diagnostic Interview (CIDI) according to DSM-IV criteria and classified by latent profile analysis on depressive symptom severity, cognitive domains and physical frailty. We estimated the hazard rate of mortality for the four depressed subgroups compared to non-depressed persons by applying Cox-regression analyses. Models were adjusted for age, sex and education as confounders and for explanatory variables per pathway in separate models: somatic burden, lifestyle characteristics, vascular burden or inflammation markers., Results: A total of 61/375 (16.3%) depressed patients and 8/132 (6.1%) non-depressed persons died during the 6-year follow-up. Two of the four subgroups (n = 186/375 (50%) of the depressed sample) had a higher hazard rate (HR) for mortality compared to non-depressed participants, that is, frail-depressed patients (HR = 5.25, [95%-CI: 2.13-13.0]) and pure mild depressed patients (HR = 3.32 [95%-CI: 1.46-7.58]) adjusted for confounders. Adding possible underlying pathways did not explain these associations., Conclusions: Age-related features (the presence of physical and cognitive frailty) contribute to the increased mortality risk in late-life depression. Future studies in depressed older patients should study the additional value of a clinical geriatric assessment and integrated treatment aimed to at reduce frailty and ameliorate their mortality risk., (© 2024 John Wiley & Sons Ltd.)

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.)

Objective: Conceptualize successful treatment of persons with dementia and severe challenging behavior as perceived by professionals., Methods: In this concept mapping study 82 experts in dementia care participated. The study followed two phases of data collection: (1) an online brainstorm where participants completed the focus prompt: ' I consider the treatment of people with severe challenging behavior in dementia successful if.' ; (2) individual sorting and rating of the collected statements followed by data analysis using multidimensional scaling and hierarchical cluster analysis, resulting in a concept map., Results: Three clusters were identified, the first addressing treatment outcomes and the latter two addressing treatment processes, each divided into sub-clusters: (1) well-being, comprising well-being of the person with dementia and all people directly involved ; (2) multidisciplinary analysis and treatment , comprising multidisciplinary analysis, process conditions, reduction in psychotropic drugs, and person-centered treatment; and (3) attitudes and skills of those involved , comprising consistent approach by the team, understanding behavior, knowing how to respond to behavior, and open attitudes ., Conclusions: Successful treatment in people with dementia and severe challenging behavior focuses on well-being of all people involved wherein attention to treatment processes including process conditions is essential to achieve this.

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.

Objectives: To evaluate the feasibility, usability and clinical value of daily diary assessments combined with actigraphy in older persons with cognitive impairment., Methods: For 63 days, patients ≥60 years with cognitive impairments filled out a daily diary (including standardized questionnaires and cognitive test battery), and wore an actiwatch (sleep). After the study, participants and clinicians received personal feedback about patterns and daily triggers of depressive symptoms, sleep and cognitive performance. We assessed feasibility (participation rate, compliance and subjective burden), usability (variability and floor- or ceiling effects) and clinical value for patients and their clinicians (questionnaires)., Results: Of 96 eligible patients, 13 agreed to participate (13.5%). One patient dropped out after 2 days, another after 37 days, and another did not complete the cognitive test battery. Compliance rate was high (6.7-10% missing values). Subjective burden was relatively low. Time-series data showed sufficient variability and no floor- or ceiling effects, except for one relevant ceiling effect on the One Back task. The personal feedback report was considered insightful by 4 out of 11 participants and 5 out of 7 clinicians., Conclusion: Daily assessments are suitable for a minority of cognitively impaired older persons, but is helpful to increase insight into their symptoms.

Background: Traditional cardiovascular risk indicators only partially explain cardiovascular risks in depressed persons. Depressed persons may exhibit a profile of cardiovascular risk indicators that goes beyond traditional cardiovascular risk indicators, such as symptom severity, insomnia, loneliness and neuroticism, yet research on the added value of these depression-related characteristics in predicting cardiovascular risks of depressed persons is scarce., Methods: Data from N = 1028 depressed Dutch adults without prevalent CVD were derived from two longitudinal depression cohort studies. The outcome was medication-confirmed self-reported CVD. Fifteen depression-related clinical and psychological characteristics were included and tested against traditional cardiovascular risk indicators. Data were analysed using Cox regression models. Incremental values of these characteristics were calculated using c-statistics., Results: After a median follow-up of 65.3 months, 12.7% of the participants developed CVD. Only anxiety and depressive symptom severity were associated with incident CVD beyond traditional cardiovascular risk indicators. The c-statistic of the model with traditional cardiovascular risk indicators was 85.47%. This increased with 0.56 or 0.33 percentage points after inclusion of anxiety or depression severity, respectively., Limitations: Other relevant depression-related characteristics were not available in the datasets used., Conclusion: Anxiety and depressive symptom severity were indicative of an increased cardiovascular risk. Including these as additional risk indicators barely improved the ability to assess cardiovascular risks in depressed persons. Although traditional cardiovascular risk indicators performed well in depressed persons, existing risk prediction algorithms need to be validated in depressed persons., Competing Interests: Conflict of interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

We aimed to explore the heterogeneity of schema therapy regarding (a) patient characteristics, (b) content, and (c) way of delivering schema therapy. A search was conducted of the electronic databases EMBASE, PsycINFO, Web of Science, MEDLINE, and COCHRANE up to June 15, 2022. Treatment studies were eligible if they (a) used schema therapy as (component of) the intervention examined, and (b) reported an outcome measure quantitatively. A total of 101 studies met the inclusion criteria, including randomized controlled trials ( n = 30), non-randomized controlled trials ( n = 8), pre-post designs ( n = 22), cases series ( n = 13), and case reports (n = 28), including 4006 patients. Good feasibility was consistently reported irrespective of format (group versus individual), setting (outpatient, day-treatment, inpatient), intensity of treatment, and the specific therapeutic components included. Schema therapy was applied to various (psychiatric) disorders. All studies presented promising results. Effectiveness of the different models of schema therapy as well as application beyond personality disorders should be examined more rigorously.

The vascular apathy hypothesis states that cerebral small vessel disease (CSVD) can cause apathy, even when no other symptoms of CSVD are present. In order to examine this hypothesis, the objectives of this narrative review are to evaluate the evidence for a pathophysiological mechanism linking CSVD to apathy and to examine whether CSVD can be a sole cause of apathy. The nature of the CSVD-apathy relationship was evaluated using the Bradford Hill criteria as a method for research on the distinction between association and causation. Pathological, neuroimaging, and behavioral studies show that CSVD can cause lesions in the reward network, which causes an apathy syndrome. Studies in healthy older individuals, stroke patients and cognitively impaired persons consistently show an association between CSVD markers and apathy, although studies in older persons suffering from depression are inconclusive. A biological gradient is confirmed, as well as a temporal relationship, although the evidence for the latter is still weak. The specificity of this causal relationship is low given there often are other contributing factors in CSVD patients with apathy, particularly depression and cognitive deterioration. Differentiating between vascular apathy and other apathy syndromes on the basis of clinical features is not yet possible, while in-depth knowledge about differences in the prognosis and efficacy of treatment options for apathy caused by CSVD and other apathy syndromes is lacking. Since we cannot differentiate between etiologically different apathy syndromes as yet, it is premature to use the term vascular apathy which would suggest a distinct clinical apathy syndrome., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

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.)

Objectives: Determinants of frailty are generally explored within context of somatic healthcare and/or lifestyle characteristics. To examine the impact of personality traits on change in frailty and the potential role of depression., Methods: A 2-year follow-up study including 285 patients with a depressive disorder and 116 never-depressed controls. Multiple linear regression analyses were conducted to regress the Big Five personality traits (independent variables) on different frailty measures (dependent variables), including the Frailty Index, Frailty phenotype, gait speed, and handgrip strength. Analyses were adjusted for confounders (with and without depressive disorder) and baseline frailty severity. Interactions between personality traits and depressive disorder were examined., Results: All personality traits were associated with change in at least one frailty marker over time. Over time, a higher level of neuroticism was associated with an accelerated increase of frailty, whereas a higher level of extraversion, agreeableness, conscientiousness and openness were associated with an attenuated increase of frailty. None of the associations were moderated by depression. Additional adjustment for depression decreased the strength of the association of neuroticism, extraversion and conscientiousness with frailty., Conclusions: Personality traits have impact on frailty trajectories in later life., Clinical Implications: Underlying pathways and potential modification by psychotherapy merit further study.

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.)

Objective: We aimed to evaluate the prevalence, clinical determinants, and consequences (falls and hospitalization) of frailty in older adults with mental illness., Design: Retrospective clinical cohort study., Setting: We collected the data in a specialized psychogeriatric ward, in Boston, USA, between July 2018 and June 2019., Participants: Two hundred and fourty-four inpatients aged 65 years old and over., Measurements: Psychiatric diagnosis was based on a multi-professional consensus meeting according to DSM-5 criteria. Frailty was assessed according to two common instruments, that is, the FRAIL questionnaire and the deficit accumulation model (aka Frailty Index [FI]). Multiple linear regression analyses were conducted to evaluate the association between frailty and sample demographics (age, female sex, and non-Caucasian ethnicity) and clinical characteristics (dementia, number of clinical diseases, current infection, number of psychotropic, and non-psychotropic medications in use). Multiple regression between frailty assessments and either falls or number of hospital admissions in the last 6 and 12 months, respectively, were analyzed and adjusted for covariates., Results: Prevalence of frailty was high, that is, 83.6% according to the FI and 55.3% according to the FRAIL questionnaire. Age, the number of clinical (somatic) diseases, and the number of non-psychotropic medications were independently associated with frailty identified by the FRAIL. Dementia, current infection, the number of clinical (somatic) diseases, and the number of non-psychotropic medications were independently associated with frailty according to the FI. Falls were significantly associated with both frailty instruments. However, we found only a significant association for the number of hospital admissions with the FI., Conclusion: Frailty is highly prevalent among geriatric psychiatry inpatients. The FRAIL questionnaire and the FI may capture different forms of frailty dimensions, being the former probably more associated with the phenotype model and the latter more associated with multimorbidity.

Objectives: Previous studies on the interrelationship between sleep and agitation relied on group-aggregates and so results may not be applicable to individuals. This proof-of-concept study presents the single-subject study design with time series analysis as a method to evaluate the association between sleep and agitation in individual nursing home residents using actigraphy., Method: To record activity, three women and two men (aged 78-89 years) wore the MotionWatch 8© (MW8) for 9 consecutive weeks. Total sleep time and agitation were derived from the MW8 data. We performed time series analysis for each individual separately. To gain insight into the experiences with the actigraphy measurements, care staff filled out an investigator-developed questionnaire on their and participants' MW8 experiences., Results: A statistically significant temporal association between sleep and agitation was present in three out of five participants. More agitation was followed by more sleep for participant 1, and by less sleep for participant 4. As for participants 3 and 4, more sleep was followed by more agitation. Two-thirds of the care staff members (16/24) were positive about the use of the MW8. Acceptability of the MW8 was mixed: two residents refused to wear the MW8 thus did not participate, one participant initially experienced the MW8 as somewhat unpleasant, while four participants seemed to experience no substantial problems., Conclusion: A single-subject approach with time series analysis can be a valuable tool to gain insight into the temporal relationship between sleep and agitation in individual nursing home residents with dementia experiencing sleep disturbance and agitation.

Objectives: Decision making (DM) is a component of executive functioning, essential for choosing appropriate decisions. Executive dysfunctioning is particularly common in late-life depression, however the literature is scarce on DM. This case-control study aimed to evaluate the DM profile and performance in participants with and without unipolar major depression., Method: The DM profile and performance were assessed by the Melbourne Decision Making Questionnaire and the Iowa Gambling Task (IGT), respectively, in three groups of older adults from a university-based geriatric psychiatry clinic, i.e. current depression ( n  = 30), remitted depression ( n  = 43) and healthy controls ( n  = 59). The Hamilton Depression scale (HAM-D) 21 items, the Hamilton Anxiety scale, and the Mini-Mental State Examination were used to access depressive symptoms, anxiety symptoms, and cognitive impairment, respectively. Multinomial, nominal and binary logistic regression was used to evaluate the associations between depression, depressive symptomatology and DM., Results: In comparison to the control group, patients with current depression presented higher scores in buck-passing and proscratination DM profiles. In the hypervigilance profile, there was a significant difference between current and remitted depression groups. A higher value ​in the HAM-D scale increased the probability of disadvantageous DM profiles. Depressive patients showed a tendency of a higher mean score in both disadvantageous decks (A and B) of IGT. Patients with current depression showed a worse performance compared to the remitted depression group in the IGT netscore., Conclusion: Older adults with current depression showed DM profiles considered maladaptive or disadvantageous compared to both remitted depression and healthy controls groups.

Depression is one of the most prevalent mental disorders in older adults and leads to considerable decreases in health, well-being, and impaired functioning. Intervention studies have focused on the effects on symptomatic recovery, and most do not include functional recovery as an outcome. Reduction of functional limitations as a treatment goal in old-age psychiatry aligns with the values of older persons. The objective of this review was therefore to evaluate the effectiveness of late-life depression interventions on functional limitations. This systematic review identified 15 randomized controlled trials in which the effectiveness of different interventions on functional limitations was evaluated in patients with late-life depression. The interventions were categorized into four categories: psychological interventions, drug treatment, physical exercise, and collaborative care. Multicomponent and collaborative-care interventions appear to be the most promising for improvement of functional limitations, particularly in primary care and community-dwelling populations of older persons with symptoms of depression. There is, however, a lack of evidence regarding studies in specialized mental health care., (© 2022 The Authors. International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

Objectives: Schema group therapy is an effective treatment for personality disorders, but its focus on cognitive techniques may be a limitation for older adults. This article describes the rationale and initial evaluation of a group schema therapy protocol enriched with psychomotor therapy (GST+PMT) for older adults in geriatric mental health care., Methods: Within an observational feasibility study, we evaluated the effect of a 26-week GST+PMT program in 19 outpatients aged 60-70 years with a cluster B or C personality disorder on the Young Schema Questionnaire, Schema Mode Inventory and Manchester Short Assessment of Quality of Life. Cohen's d effect-sizes were calculated between baseline (T0), mid-treatment (T1) and end-of-treatment (T2)., Results: Medium to large pre-post effect-sizes (T0-T2) were found for all outcome measures. Most improvement of schema modes occurred between T0-T1, and of schemas and quality of life between T1-T2., Conclusions: Group schema therapy enriched with PMT is feasible in later life and its effect might be mediated by targeting schema modes. Future research would be helpful, including larger samples and controlled studies., Clinical Implications: For older adults suffering from personality disorders B or C verbal schema group therapy enriched with non-verbal PMT may be an effective treatment.

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.)

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., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Aprahamian et al.)

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.)

Objectives: Much is unknown about the combination of Medically Unexplained Symptoms (MUS) and alexithymia in later life, but it may culminate in a high disease burden for older patients. In the present study we assess the prevalence of alexithymia in older patients with either MUS or Medically Explained Symptoms (MES) and we explore physical, psychological and social correlates of alexithymia., Methods and Design: A case control study was performed. We recruited older persons (>60 years) with MUS (N = 118) or MES (N = 154) from the general public, general practitioner clinics and hospitals. Alexithymia was measured by the 20-item Toronto Alexithymia Scale, correlates were measured by various questionnaires., Results: Prevalence and severity of alexithymia were higher among older persons with MUS compared to MES. Alexithymia prevalence in the MUS subgroup was 23.7%. We found no association between alexithymia and increasing age. Alexithymia was associated with depressive symptoms, especially in the MUS population., Conclusions: Alexithymia prevalence was lower than generally found in younger patients with somatoform disorder, but comparable to studies with similar diagnostic methods for MUS. Considering the high prevalence and presumed etiological impact of alexithymia in older patients with MUS, as well as its association with depression, this stresses the need to develop better understanding of the associations between alexithymia, MUS and depression in later life., (© 2022 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

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).)

Objectives: To investigate the presence, nature and direction of the daily temporal association between depressive symptoms, cognitive performance and sleep in older individuals., Design, Setting, Participants: Single-subject study design in eight older adults with cognitive impairments and depressive symptoms., Measurements: For 63 consecutive days, depressive symptoms, working memory performance and night-time sleep duration were daily assessed with an electronic diary and actigraphy. The temporal associations of depressive symptoms, working memory and total sleep time were evaluated for each participant separately with time-series analysis (vector autoregressive modeling)., Results: For seven out of eight participants we found a temporal association between depressive symptoms and/or sleep and/or working memory performance. More depressive symptoms were preceded by longer sleep duration in one person (r = 0.39; p < .001), by longer or shorter sleep duration than usual in one other person (B = 0.49; p < .001), by worse working memory in one person (B = -0.45; p = .007), and by better working memory performance in one other person (B = 0.35; p = .009). Worse working memory performance was preceded by longer sleep duration (r = -.35; p = .005) in one person, by shorter or longer sleep duration in three other persons (B = -0.76; p = .005, B = -0.61; p < .001; B = -0.34; p = .002), and by more depressive symptoms in one person (B = -0.25; p = .009)., Conclusion: The presence, nature and direction of the temporal associations between depressive symptoms, cognitive performance and sleep differed between individuals. Knowledge of personal temporal associations may be valuable for the development of personalized intervention strategies in order to maintain their health, quality of life, functional outcomes and independence.

Objectives: Accumulating evidence shows depression as a risk factor for frailty, but studies are mainly population-based and widely differ in their assessment of either depression or frailty. We investigated the association between depression and frailty among geriatric outpatients using different assessment instruments for both conditions., Method: Among 315 geriatric outpatients (mean age 72.1 years, 68.3% female sex) participating the MiMiCS-FRAIL cohort study, major and subthreshold depression were measured with psychiatric diagnostic interview according to DSM-5 criteria (SCID-5) as well as with instruments to screen and measure severity of depressive symptoms (GDS-15 and PHQ-9). Frailty was assessed according to a screening instrument (FRAIL-BR) and a multidimensional Frailty Index (FI-36 items). Multiple logistic and linear regression were performed to assess the association between depression (independent variable) and frailty (dependent variable) adjusted for confounders., Results: Frailty prevalence in patients with no, subthreshold or major depressive disorder increases from either 14.5%, 46.5% to 65.1% when using the FRAIL-BR questionnaire, and from 10.2%, 20.9%, to 30.2% when using the FI-36 index. These association remain nearly the same when adjusted for covariates. Both the FRAIL-BR and the FI-36 were strongly associated with major depressive disorder, subthreshold depression, and depressive symptoms by PHQ-9 and GDS-15., Conclusion: Late life depression and frailty are associated in a dose-dependent manner, irrespective of the used definitions. Nonetheless, to avoid residual confounding, future research on underlying biological mechanisms should preferably be based on formal psychiatric diagnoses and objectively assessment frailty status.

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.)

Background: Vitamin D deficiency is a universal risk factor for adverse health outcomes. Since depression is consistently associated with low vitamin D levels as well as several adverse health outcomes, vitamin D supplementation may be especially relevant for depressed persons. This review examines the potential benefits of vitamin D for (somatic) health outcomes in randomised controlled supplementation trials for depression., Method: Systematic literature search to assess whether adverse health outcomes, such as frailty, falls, or cognitive functioning, were included in vitamin D supplementation trials for depression, and whether these outcomes were affected by supplementation. The revised Cochrane tool for assessing risk of bias in randomised trials was used., Results: Thirty-one trials were included. Adverse health outcomes were considered in five studies. Two studies reported some beneficial effect on an adverse health outcome., Conclusions and Implications: While depressed persons are at increased risk of vitamin D deficiency, supplementation trials hardly addressed the common negative health consequences of low vitamin D levels as secondary outcome measures. Well-designed trials of the effects of vitamin D supplementation in late-life depression should explore whether adverse health outcomes can be prevented or stabilised, and whether depression benefits from this improvement., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Frailty marks a process of increasing dysregulation of physiological systems which increases the risk of adverse health outcomes. This study examines the hypothesis that the association between multiple cardiovascular risk factors (CVRF) and cardiovascular diseases (CVD) becomes stronger with increasing frailty severity., Methods: Cross-sectional analysis of 339 older adults (55.2% women; aged 75.2 ± 9.1 years) from an outpatient geriatric clinic from a middle-income country. The frailty index (FI) was calculated as the proportion of 30 possible health deficits. We assessed hypertension, diabetes, obesity, dyslipidemia, sedentarism and smoking as CVRF (determinants) and myocardial infarction, stroke, heart failure as CVD. Poisson regression models adjusted for age, sex, and education was applied to estimate the association between frailty as well as CVRF (independent variables) with CVD (dependent variable)., Results: Of the 339 patients, 18,3% were frail (FI ≥ 0.25) and 32.7% had at least one CVD. Both frailty and CVRF were significantly associated with CVD (PR = 1.03, 95% CI 1.01 to 1.05; p = 0.001, and PR = 1.46, 95% 1.24 to 1.71; p < 0.001, respectively) adjusted for covariates. The strength of the association between CVRF and CVD decreased with increasing frailty levels, as indicated by a significant interaction term of frailty and CVRF (p < 0.001)., Conclusion: Frailty and CVRF are both associated with CVD, but the impact of CVRF decreases in the presence of frailty. When confirmed in longitudinal studies, randomized controlled trials or causal inference methods like Mendelian randomization should be applied to assess whether a shift from traditional CVRF to frailty would improve cardiovascular outcome in the oldest old., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.)

Objectives: While vitamin D is involved in frailty as well as depression, hardly any study has examined the course of vitamin D levels prospectively. The objective of this study is to examine whether a change of vitamin D in depressed older adults is associated with either depression course, course of frailty, or both., Methods: The study population consisted of 232 of 378 older adults (60-93 years) with a DSM-IV defined depressive disorder participating in the Netherlands Study of Depression in Older persons, a prospective clinical cohort study. Baseline and 2-year follow-up data on depressive disorder (DSM-IV diagnosis), symptom severity (inventory of depressive symptoms), frailty phenotype (and its individual components) and vitamin D levels were obtained. Linear mixed models were used to study the association of change in vitamin D levels with depression course, course of frailty, and the combination., Results: Vitamin D levels decreased from baseline to follow-up, independent from depression course. An increase in frailty was associated with a significantly sharper decrease of vitamin D levels over time. Post hoc analyses showed that this association with frailty might be driven by an increase of exhaustion over time and counteracted by an increase in walking speed., Conclusions: Our findings generate the hypothesis that vitamin D supplementation in late-life depression may improve frailty, which may partly explain inconsistent findings of randomised controlled trials evaluating the effect of vitamin D for depression. We advocate to consider frailty (components) as an outcome in future supplementation trials in late-life depression., (© 2021 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Objective: Studies on the course of depression often ignore comorbid anxiety disorders or anxiety symptoms. We explored predictors of complete remission (no depression nor anxiety diagnoses at follow-up) and of the course of comorbid anxiety symptoms. We additionally tested the hypothesis that the course of anxiety disorders and symptoms in depressed patients is explained by negative life-events in the presence of high neuroticism or a low sense of mastery., Methods: An observational study of 270 patients (≥60 years) diagnosed with major depressive disorder and 2-year follow-up data, who participated in the Netherlands Study of Depression in Older persons (NESDO). Sociodemographic, somatic, psychiatric, and treatment variables were first explored as possible predictors. A multiple logistic regression analysis was used to examine their predictive value concerning complete remission. Subsequently, negative life-events, personality and their interaction were tested as potential predictors. Linear Mixed Models were used to assess whether the personality traits modified the effect of early and recent life-events, and time and their interactions on the course of the anxiety symptoms., Results: A total of 135 of 270 patients achieved complete remission. Depressed patients with a comorbid anxiety disorder at baseline less often achieved complete remission: 38 of 103 (37.0%) versus 97 of 167 (58.1%). The severity of depressive and anxiety symptomatology, the presence of a comorbid anxiety disorder, and a poorer physical health at baseline predicted nonremission. In line with our hypothesis, a less favorable course of self-reported anxiety symptoms was associated with more recent negative life-events, but only among patients with a high level of neuroticism or a low level of mastery., Conclusion: Comorbid anxiety in depression as a negative impact on complete remission at 2-year follow-up. The course of anxiety severity seems dependent on the interaction of personality traits and life-events., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Frailty is a clinical phenotype that predicts negative health outcomes, including mortality, and is increasingly used for risk stratification in geriatric medicine. Similar to frailty, late-life depression is also associated with increased mortality rates. Therefore, we examined whether frailty and frailty-related biomarkers predict mortality among depressed older patients., Methods: In our study of 378 older patients aged ≥ 60 years with a depressive disorder (DSM-IV criteria), we examined whether frailty predicts time-to-death during a 6-year follow-up using Cox proportional hazard regression analyses adjusted for confounders. Baseline data were collected from 2007 to September 2010. Frailty was defined according to the Fried Frailty Phenotype criteria (muscle weakness, slowness, exhaustion, low activity level, unintended weight loss). Similarly, we examined the predictive value of 3 inflammatory markers, vitamin D level, and leukocyte telomere length and whether these effects were independent of the frailty phenotype., Results: During follow-up, 27 (26.2%) of 103 frail depressed patients died compared with 35 (12.7%) of 275 non-frail depressed patients (P < .001). Adjusted for confounders, the number of frailty components was associated with an increased mortality rate (hazard ratio = 1.38 [95% CI, 1.06-1.78], P = .015). All biomarkers except for interleukin 6 were prospectively associated with mortality, but only higher levels of high-sensitivity C-reactive protein and lower levels of vitamin D were independent of frailty associated with mortality., Conclusions: In late-life depression, frailty identifies older patients at increased risk of adverse negative health outcomes. Therefore, among frail depressed patients, treatment models that include frailty-specific interventions might reduce mortality rates., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Objective: Depression has been associated with increased mortality rates, and modifying mechanisms have not yet been elucidated. We examined whether specific subtypes or characteristics of late-life depression predict mortality., Methods: A cohort study including 378 depressed older patients according to DSM-IV criteria and 132 never depressed comparisons. The predictive value of depression subtypes and characteristics on the six-year mortality rate, as well as their interaction with somatic disease burden and antidepressant drug use, were studied by Cox proportional hazard analysis adjusted for demographic and lifestyle characteristics., Results: Depressed persons had a higher mortality risk than non-depressed comparisons (HR = 2.95 [95% CI: 1.41-6.16], p = .004), which lost significance after adjustment for age, sex, education, smoking, alcohol, physical activity, number of prescribed medications and somatic comorbidity. Regarding depression subtypes and characteristics, only minor depression was associated with a higher mortality risk when adjusted for confounders (HR = 6.59 [95% CI: 1.79-24.2], p = .005)., Conclusions: Increased mortality rates of depressed older persons seem best explained by unhealthy lifestyle characteristics and multiple drug prescriptions. The high mortality rate in minor depression, independent of these factors, might point to another, yet unknown, pathway towards mortality for this depression subtype. An explanation might be that minor depression in later life reflects depressive symptoms due to underlying aging-related processes, such as inflammation-based sickness behavior, frailty, and mild cognitive impairment, which have all been associated with increased mortality.

Objectives: This study aimed to investigate whether frailty could be an explanatory factor of the association between depression and the number of geriatric syndromes., Methods: Cross-sectional baseline data from a cohort study (MiMiCS-FRAIL) were analyzed in a sample of 315 older adults. Depression was measured according to DSM-5 criteria and a self-report questionnaire (PHQ-9). Frailty was assessed according to the FRAIL questionnaire and a 30-item Frailty Index (FI). We considered six geriatric syndromes. Multiple linear regression analyses were performed and adjusted for potential confounders., Results: Multiple linear regression analyses yielded significant associations between depression and geriatric syndromes. These associations decreased substantially in strength when frailty was added to the models. Findings were consistent for different definitions of depression and frailty., Conclusions: Among depressed patients, frailty may be hypothesized as a causal pathway toward adverse health outcomes associated with depression. Longitudinal studies should explore the causality of this association., Clinical Implications: Frailty should be treated or prevented in order to minimize the impact of other geriatric syndromes among depressed older adults. Screening for frailty would be of utmost importance in mental health care, as frailty is neglected especially in this field. Integrated care models are crucial for clinical practice in mental illness care.

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/ .

Background: With increasing age, symptoms of depression may increasingly overlap with age-related physical frailty and cognitive decline. We aim to identify late-life-related subtypes of depression based on measures of depressive symptom dimensions, cognitive performance, and physical frailty., Methods: A clinical cohort study of 375 depressed older patients with a DSM-IV depressive disorder (acronym NESDO). A latent profile analysis was applied on the three subscales of the Inventory of Depressive Symptomatology, as well as performance in five cognitive domains and two proxies for physical frailty. For each class, we investigated remission, dropout, and mortality at 2-year follow-up as well as change over time of depressive symptom severity, cognitive performance, and physical frailty., Results: A latent profile analysis model with five classes best described the data, yielding two subgroups suffering from pure depression ("mild" and "severe" depression, 55% of all patients) and three subgroups characterized by a specific profile of cognitive and physical frailty features, labeled as "amnestic depression," "frail-depressed, physically dominated," and "frail-depressed, cognitively dominated." The prospective analyses showed that patients in the subgroup of "mild depression" and "amnestic depression" had the highest remission rates, whereas patients in both frail-depressed subgroups had the highest mortality rates., Conclusions: Late-life depression can be subtyped by specific combinations of age-related clinical features, which seems to have prospective relevance. Subtyping according to the cognitive profile and physical frailty may be relevant for studies examining underlying disease processes as well as to stratify treatment studies on the effectiveness of antidepressants, psychotherapy, and augmentation with geriatric rehabilitation., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.)

Objectives: Assessing late-life anxiety using an instrument with sound psychometric properties including cross-cultural invariance is essential for cross-national aging research and clinical assessment. To date, no cross-national research studies have examined the psychometric properties of the frequently used Geriatric Anxiety Inventory (GAI) in depth., Method: Using data from 3,731 older adults from 10 national samples (Australia, Brazil, Canada, The Netherlands, Norway, Portugal, Spain, Singapore, Thailand, and United States), this study used bifactor modeling to analyze the dimensionality of the GAI. We evaluated the "fitness" of individual items based on the explained common variance for each item across all nations. In addition, a multigroup confirmatory factor analysis was applied, testing for measurement invariance across the samples., Results: Across samples, the presence of a strong G factor provides support that a general factor is of primary importance, rather than subfactors. That is, the data support a primarily unidimensional representation of the GAI, still acknowledging the presence of multidimensional factors. A GAI score in one of the countries would be directly comparable to a GAI score in any of the other countries tested, perhaps with the exception of Singapore., Discussion: Although several items demonstrated relatively weak common variance with the general factor, the unidimensional structure remained strong even with these items retained. Thus, it is recommended that the GAI be administered using all items., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To examine the association of social network size and loneliness with cognitive performance and -decline in depressed older adults. Method: A sample of 378 older adults [70.7 (7.4) years] with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of current depressive disorder were recruited from primary care and specialized mental health care. Cognitive performance was assessed at baseline and 2 years follow-up with the Stroop colored-word test, a modified version of the Auditory Verbal Learning Task and the Digit Span subtest from the Wechsler Adult Intelligence Scale, encompassing four cognitive domains; processing speed, interference control, memory, and working memory. Social network size was assessed with the Close Person Inventory and loneliness with the de Jong Gierveld Loneliness Scale at baseline. Results: After adjusting for baseline working memory performance, loneliness was associated with impaired working memory after 2 years [B = -0.08 (-0.17 to 0.00)]. This association was no longer significant after adjusting for age, sex, education level, physical activity, alcohol use and depressive symptom severity [B = -0.07 (-0.16 to 0.03)]. A backward elimination procedure revealed education level to be the only covariable to explain this association. Loneliness was not associated with impairments or decline in other cognitive domains. Social network size was not associated with cognitive impairments or decline. Conclusion: Social network size and loneliness do not predict cognitive decline in depressed older adults.

Objectives: Older adults with psychiatric disorders have a substantially lower life expectancy than age-matched controls. Knowledge of risk factors may lead to targeting treatment and interventions to reduce this gap in life expectancy. In this study, we investigated whether frailty independently predicts mortality in older patients following an acute admission to a geriatric psychiatry hospital., Methods: Clinical cohort study with a 5-year follow-up of 120 older patients admitted to a psychiatric hospital between February 2009 and September 2010. On admission, we assessed frailty with a frailty index (FI). We applied Cox regression analyses with time to death as the dependent variable, to examine whether the FI was a predictor for mortality, adjusted for age, sex, level of education, multimorbidity (Cumulative Illness Rating Scale for Geriatrics, CIRS-G scores), functional status (Barthel Index), neuropsychiatric symptoms (NPS), and severity of psychiatric symptoms at admission (Clinical Global Impressions Scale of Severity)., Results: Of the 120 patients, 63 (53%) patients were frail (FI ≥ 0.25), and 59 (49%) had died within 5 years. The FI predicted mortality with a hazard ratio (HR) of 1.78 (95% CI, 1.06-2.98) per 0.1 point increase, independent of the covariates. Co-morbidity measured by the CIRS-G and functional status measured by the Barthel Index were not significantly associated., Conclusions: Frailty was a strong predictor of mortality, independent of age, gender, multimorbidity, and functional status. This implies that frailty may be helpful in targeting inpatient psychiatric treatment and aftercare according to patients' life expectancy., (© 2020 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Objectives : Over the past decade, a trend has been noticed in the Netherlands to replace large-scaled special care units (SCUs) caring for 20-30 residents with dementia by small-scaled SCUs caring for up to 8 residents. Systematic evaluations, however, have yielded a differentiated picture of the effects. As the impact on psychotropic drug use has hardly been addressed thus far, we examined the (potential) impact of psychotropic drug use when moving residents with dementia from large-scaled to small-scaled SCUs. Methods : We conducted a non-randomized, controlled study with a six-month follow-up. Among 145 residents with dementia living a large-scaled SCUs for dementia caring for 20-30 residents per unit, a total of 77 residents were moved to small-scaled SCUs caring for up to 8 residents per unit. Psychotropic drug use, classified according to the Anatomical Therapeutic Chemical Classification (ATC) system was monitored at 2 months before replacement, as well as at 3 and 6 months thereafter. Repeated measures ANOVAs were conducted for the mean Defined Daily Doses (DDDs) of both groups. Results : No significant differences between both groups in psychotropic medication use were found over a period of 8 months. Conclusion : Prescription of psychotropic drugs does not change after a transfer from a large-scaled SCU to a small-scaled SCU of patients with moderate to severe dementia.Current Controlled Trials: ISRCTN11151241.

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

Objectives: A systematic review of the relationship between subclinical small vessel disease (SSVD) in the general population and apathy to examine the hypothesis that apathy has a vascular basis., Methods: We searched for studies on associations between apathy and SSVD, operationalized as white matter hyperintensities (WMH) or white matter diffusivity changes, lacunar infarcts, cerebral microbleeds, decreasing cortical thickness, and perivascular spaces, while also peripheral proxies for SSVD were considered, operationalized as ankle brachial pressure index (ABI), intima media thickness, arterial stiffness, cardio-femoral pulse wave velocity, hypertension, or cardiovascular disease. Only eligible retrospective and prospective observational studies conducted in the general population were included., Results: The 14 studies eligible for review examined the associations between apathy and hypertension (3), ABI (1), arterial stiffness (1), cardiovascular disease (2), WMH (3), white matter diffusivity (2), cerebral microbleeds (1), or cortical thickness (3). Arterial stiffness and white matter diffusivity were not related to apathy, while the associations with cortical thickness were contradictory. Cross-sectional studies in the general population did find evidence of apathy being associated with WMH, CM, cardiovascular disease, hypertension, and ABI, and cardiovascular disease was prospectively associated with apathy. The methodologies of the studies reviewed were too heterogeneous to perform meta-analyses., Conclusions: Although more prospective evidence is needed and vascular depression needs to be controlled for, cardiovascular disease, hypertension, and ABI as proxies for SSVD, and WMH and cerebral microbleeds as direct measures of SSVD have been found to be associated with apathy in the general population, supporting the hypothesis of vascular apathy., (© 2019 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Purpose/background: The duration of untreated depression is a predictor for poor future prognosis, making rapid dose finding essential. Genetic variation of the CYP2D6 isoenzyme can influence the optimal dosage needed for individual patients. The aim of this study was to determine the effectiveness of CYP2D6 pharmacogenetic screening to accelerate drug dosing in older patients with depression initiating nortriptyline or venlafaxine., Methods/procedures: In this randomized controlled trial, patients were randomly allocated to one of the study arms. In the intervention arm (DG-I), the specific genotype accompanied by a standardized dosing recommendation based on the patients' genotype and the prescribed drug was directly communicated to the physician of the participant. In both the deviating genotype control arm (DG-C) and the nonrandomized control arm, the physician of the participants was not informed about the genotype and the associated dosing advise. The primary outcome was the time needed to reach adequate drug levels: (1) blood levels within the therapeutic range and (2) no dose adjustments within the previous 3 weeks., Findings/results: No significant difference was observed in mean time to reach adequate dose or time to adequate dose between DG-I and DG-C. Compared with the nonrandomized control arm group, adequate drug levels were reached significantly faster in the DG-I group (log-rank test; P = 0.004), and there was a similar nonsignificant trend for the DG-C group (log-rank test; P = 0.087)., Implications/conclusions: The results of this study do not support pharmacogenetic CYP2D6 screening to accelerate dose adjustment for nortriptyline and venlafaxine in older patients with depression.

Background: Metabolic syndrome (MetS) has been associated with both early- and late-life depression. This study investigated whether baseline MetS and its individual components are associated with the course of depression over six years among older persons with a formal depression diagnosis., Methods: Data were used from 378 older persons with a depressive disorder from the Netherlands Study of Depression in Old age (NESDO) with a 6-year follow-up. A formal depression diagnosis according to DSM-IV-TR criteria was ascertained with the Composite International Diagnostic Interview. Severity of depressive symptoms was assessed with the Inventory of Depressive Symptomatology at 6-month intervals. Metabolic syndrome (MetS) was defined according the modified National Cholesterol Education Programme - Adult Treatment Panel III criteria. Primary outcome was time to remission from depression. We applied cox regression analysis for the primary outcome and linear mixed models for secondary analyses., Results: Neither MetS nor its individual components were associated with time to remission from depression (MetS: HR = 1.03; 95% CI = 0.74 - 1.44; p = 0.85), or with depression severity (MetS: B = 0.02; SE = 0.04; p = 0.64) and course of depressive symptoms (MetS: B = -0.01; SE = 0.01; p = 0.23) over 6-years follow-up., Limitations: Attrition was relatively high (46.8%). Furthermore, we only had information on formal depression diagnosis at baseline, 2-year, and 6-year follow-up., Conclusions: We found no evidence for an effect of baseline presence of metabolic dysregulation on the course of formally diagnosed depression in older persons. Metabolic syndrome in depressed patients should be clinically monitored for other reasons than predicting chronicity or severity of depression., (Copyright © 2019. Published by Elsevier B.V.)

Although previous studies have underlined the protective role of social support for physical and psychological health, no self-report questionnaires are validated for measuring social support in large-scale psychiatric epidemiological studies. In the current study, we aim to validate the shortened version of the Close Persons Questionnaire (CPQ), a self-report questionnaire that is administered twice to measure social support received from the partner (CPQ-p) as well as from a close friend/family member (CPQ-f). Data of psychiatric patients (n = 1891) and controls (n = 1872) from three Dutch epidemiological studies that assessed determinants of psychopathology were used to validate the shortened CPQ. This included determining factor structure and reliability for the different scales. Using multigroup confirmatory factor analyses, a four-factor model proved to be the best fitting model for both the CPQ-p and CPQ-f. The resulting subscales -emotional support, practical support, negative support experiences, inadequacy of support-showed moderate to good reliability for both the CPQ-p and the CPQ-f, and were all correlated with other social measures in the expected directions. The shortened version of the CPQ proves to be a valid and reliable measure of social support for both psychiatric patients and controls. Further research is needed to assess usability of the shortened version of the CPQ for clinical practice., (Copyright © 2019 Elsevier Ltd. All rights reserved.)