Strengths and Weaknesses of the Vascular Apathy Hypothesis:A Narrative Review

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

Adverse health outcomes in vitamin D supplementation trials for depression:A systematic review

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

Frailty measures in immuno-metabolic subtypes of late-life depression; A two-year prospective study:A two-year prospective study

Background/Objectives - Frailty is highly prevalent with increasing age. Based on the concept of depression as a disorder of accelerated aging and its association with inflammation and metabolic dysregulation, we examined whether frailty measures at baseline and over time differed between immuno-metabolic subtypes of late-life depression. Methods - Clinical cohort study in primary and secondary mental health care with two-year follow-up. In total 359 depressed older patients (≥ 60 years) classified in four immuno-metabolic subgroups by latent profile analysis. We compared frailty measures at baseline and two-year follow-up adjusted for confounders between immuno-metabolic based depressed subgroups. Frailty measures included the frailty index, physical frailty phenotype, and two proxies (handgrip strength, gait speed). Results - At baseline, the relatively healthy depressed subgroup (n = 181) performed best on all frailty markers. While frailty markers worsened over time, the two-year course did not differ between the subgroups for any of these markers. Conclusion - The more severe immuno-metabolic dysregulation present in late-life depression, the more frail. Nonetheless, as trajectories over time did not differ between subgroups, the difference probably emerged at midlife. Future studies should examine whether geriatric assessment might become relevant at earlier ages in specialized mental health care

A prospective study into change of vitamin D levels, depression and frailty among depressed older persons

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

(Vi)-rushed Into Online Group Schema Therapy Based Day-Treatment for Older Adults by the COVID-19 Outbreak in the Netherlands

BACKGROUND: Societal measures in context of the COVID-19 outbreak forced us to transform our schema therapy based day-treatment for older adults with chronic affective disorders and personality problems into an online program. The objective of this paper is to present first impressions of this transformation. METHODS: Using over-the-phone instructions initially, all patients were able to participate with the online therapy program. To reduce screen-time for patients, the nonverbal therapies were shortened. Four patients, aged 64-70 years, started our online program. RESULTS: Therapists were positive about the online capabilities and resilience of patients to adapt to the new situation. Prejudices on limited effectiveness of online psychotherapy were counteracted. Sending homework by email and mail seems to facilitate therapy adherence. Nonverbal therapy could be important to stimulate the online group process. CONCLUSION: We were positively surprised by the online capabilities of our geriatric mental healthcare patients and encourage further formal effectiveness studies

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

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

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

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

Euthanasia in Dementia: A Narrative Review of Legislation and Practices in the Netherlands and Belgium

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