Effects of the discontinuation of antihypertensive treatment on neuropsychiatric symptoms and quality of life in nursing home residents with dementia (DANTON): a multicentre, open-label, blinded-outcome, randomised controlled trial.

BACKGROUND: Based on observational studies and randomised controlled trials (RCTs), the benefit-harm balance of antihypertensive treatment in older adults with dementia is unclear. OBJECTIVE: To assess whether discontinuing antihypertensive treatment reduces neuropsychiatric symptoms (NPSs) and maintains quality of life (QoL) in nursing home residents with dementia. DESIGN: Open-label, blinded-outcome RCT. Randomisation 1:1, stratified by nursing home organisation and baseline NPS. Trial registration: NL7365. SUBJECTS: Dutch long-term care residents with moderate-to-severe dementia and systolic blood pressure (SBP) ≤160 mmHg during antihypertensive treatment. Exclusion criteria included heart failure NYHA-class-III/IV, recent cardiovascular events/procedures or life expectancy <4 months (planned sample size n = 492). MEASUREMENTS: Co-primary outcomes NPS (Neuropsychiatric Inventory-Nursing Home [NPI-NH]) and QoL (Qualidem) at 16 weeks. RESULTS: From 9 November 2018 to 4 May 2021, 205 participants (median age 85.8 [IQR 79.6-89.5] years; 79.5% female; median SBP 134 [IQR 123-146] mmHg) were randomised to either antihypertensive treatment discontinuation (n = 101) or usual care (n = 104). Safety concerns, combined with lacking benefits, prompted the data safety and monitoring board to advice a premature cessation of randomisation. At 16-week follow-up, no significant differences were found between groups for NPI-NH (adjusted mean difference 1.6 [95% CI -2.3 to 5.6]; P = 0.42) or Qualidem (adjusted mean difference - 2.5 [95% CI -6.0 to 1.0]; P = 0.15). Serious adverse events (SAEs) occurred in 36% (discontinuation) and 24% (usual care) of the participants (adjusted hazard ratio 1.65 [95% CI 0.98-2.79]). All 32-week outcomes favoured usual care. CONCLUSION: Halfway through this study, a non-significant increased SAE risk associated with discontinuing antihypertensive treatment was observed, and an associated interim analysis showed that significant worthwhile health gain for discontinuation of antihypertensive treatment was unlikely. This unbeneficial benefit-harm balance shows that discontinuation of antihypertensive treatment in this context does not appear to be either safe or beneficial enough to be recommended in older adults with dementia.

Frequencies and reasons for unplanned emergency department return visits by older adults: a cohort study.

BACKGROUND: As unplanned Emergency Department (ED) return visits (URVs) are associated with adverse health outcomes in older adults, many EDs have initiated post-discharge interventions to reduce URVs. Unfortunately, most interventions fail to reduce URVs, including telephone follow-up after ED discharge, investigated in a recent trial. To understand why these interventions were not effective, we analyzed patient and ED visit characteristics and reasons for URVs within 30 days for patients aged ≥ 70 years. METHODS: Data was used from a randomized controlled trial, investigating whether telephone follow-up after ED discharge reduced URVs compared to a satisfaction survey call. Only observational data from control group patients were used. Patient and index ED visit characteristics were compared between patients with and without URVs. Two independent researchers determined the reasons for URVs and categorized them into: patient-related, illness-related, new complaints and other reasons. Associations were examined between the number of URVs per patient and the categories of reasons for URVs. RESULTS: Of the 1659 patients, 222 (13.4%) had at least one URV within 30 days. Male sex, ED visit in the 30 days before the index ED visit, triage category "urgent", longer length of ED stay, urinary tract problems, and dyspnea were associated with URVs. Of the 222 patients with an URV, 31 (14%) returned for patient-related reasons, 95 (43%) for illness-related reasons, 76 (34%) for a new complaint and 20 (9%) for other reasons. URVs of patients who returned ≥ 3 times were mostly illness-related (72%). CONCLUSION: As the majority of patients had an URV for illness-related reasons or new complaints, these data fuel the discussion as to whether URVs can or should be prevented. TRIAL REGISTRATION: For this cohort study, we used data from a randomized controlled trial (RCT). This trial was pre-registered in the Netherlands Trial Register with number NTR6815 on the 7th of November 2017.

Symptom Profile and Clinical Course of Inpatients with Unipolar versus Bipolar Depression.

BACKGROUND: Although differences in symptom profiles and outcome between depressive patients with an underlying major depressive disorder (MDD) and bipolar depression (BD) have been reported, studies with sequential short-interval assessments in a real-life inpatient setting are scarce. OBJECTIVES: To examine potential differences in symptom profile and course of depressive symptomatology in depressive inpatients with underlying MDD and BD. METHODS: A cohort of 276 consecutive inpatients with MDD (n = 224) or BD (n = 52) was followed during their hospitalization using routine outcome monitoring (ROM), which included a structured diagnostic interview at baseline (Mini-International Neuropsychiatric Interview Plus [MINI-Plus]) and repeated 17-item Hamilton Depression Rating Scale every 2 weeks. MDD and BD were compared regarding their symptom profiles and time to response and remission. Furthermore, the concordance between the MINI-Plus and clinical diagnosis was analyzed. RESULTS: Patients were on average 52 and 47 years old in the MDD and BD group, respectively, and 66 versus 64% were female. Compared to patients with BD, patients with MDD scored higher on weight loss (p = 0.02), whereas the BD group showed a higher long-term likelihood of response (hazard ratio = 1.93, 95% confidence interval 1.16-3.20, p for interaction with time = 0.04). Although the same association was seen for remission, the interaction with time was not significant (p = 0.48). Efficiency between the MINI-Plus and clinical diagnosis of BD was high (0.90), suggesting that the MINI-Plus is an adequate ROM diagnostic tool. CONCLUSIONS: In routine clinical inpatient care, minor differences in the symptom profile and the course of depressive symptomatology may be helpful in distinguishing MDD and BD, particularly when using sequential ROM assessments.

Routine alcohol screening in the ED: unscreened patients have an increased risk for hazardous alcohol use.

BACKGROUND: Routine screening programmes for hazardous alcohol use in the ED miss large numbers of patients. We investigated whether patient-related or staff-related factors cause screening failures and whether unscreened patients are at increased risk of hazardous alcohol use. METHODS: This is a secondary analysis of a prospective study. From November 2012 to November 2013, all adult patients visiting a Dutch inner city ED were screened for hazardous alcohol consumption using the Alcohol Use Disorders Identification Test-Consumption. Reasons for failure of screening were categorised as: (A) patient is unable to cooperate (due to illness or pain, decreased consciousness or incomprehension due to intoxication, psychiatric, cognitive or neurological disorder or language barrier), (B) healthcare professional forgot to ask, (C) patient refuses cooperation and (D) screening was recently performed (<6 months ago). Presence of risk factors for hazardous alcohol use was compared between screened and unscreened patients. RESULTS: Of the 28 019 ED patients, 18 310 (65%) were screened and 9709 (35%) were not. In 7150 patients staff forgot to screen, whereas 2559 patients were not screened due to patient factors (2340 being unable and 219 unwilling). Patients with any of these risk factors were less likely to be screened: male sex, alcohol-related visit, any intoxication, head injury, any kind of wound and major trauma. In multivariate analysis, all these risk factors were independently associated with not being screened. Patients with at least one risk factor for hazardous alcohol use were less likely to be screened. Highest prevalence of risk factors was found in patients unable or unwilling to cooperate. CONCLUSION: Patients who do not undergo routine screening for alcohol use at triage in the ED have an increased risk for hazardous alcohol use. These data highlight the importance of screening patients, especially those initially unwilling or unable to cooperate, at a later stage.

Cognitive Deficits in Older Adults With Psychotic Depression: A Meta-Analysis.

A major depressive disorder with psychotic features, that is, psychotic depression (PD), is often accompanied by cognitive deficits, particularly in older patients. We aimed to assess to what extent various cognitive domains are affected in older patients with PD compared to those with nonpsychotic depression (NPD). Therefore, a systematic search was conducted in Medline, Embase, Web of Science, the Cumulative Index to Nursing and Allied Literature (CINAHL), Google Scholar, and Cochrane for all relevant studies. Hereafter, we conducted a meta-analysis of seven studies on cognitive deficits in older adults (55+ years), comparing patients with PD and patients with NPD. Compared to patients with NPD, those with PD not only showed a significantly poorer performance on overall cognitive function, with a Hedges' g effect size of -0.34 (95% confidence interval: -0.56; -0.12; p = 0.003), but also on nearly all separate cognitive domains, with Hedges' g effect sizes ranging from -0.26 to -0.64 (all p's <0.003), of which attention was most adversely affected. Verbal fluency showed no significant effect, although this analysis may have been underpowered. The funnel plot suggested no significant publication bias (Egger test intercept: -2.47; 95% confidence interval: -5.50; 0.55; p = 0.09). We conclude that older patients with PD show more cognitive deficits on all cognitive domains, except for verbal fluency, compared to patients with NPD. It is crucial that clinicians and researchers take cognitive deficits into consideration in older adults with PD.

Efficacy and Tolerability of Atypical Antipsychotics in the Treatment of Delirium: A Systematic Review of the Literature.

BACKGROUND: Although haloperidol is the most widely used drug in the treatment of delirium, evidence on the relevance of atypical antipsychotics (AAPs) is growing. OBJECTIVE: To review the literature on the efficacy and tolerability of AAPs in the treatment of delirium. METHODS: A systematic search of the literature published before April 2018 was performed on PubMed using the following search strings: "Delirium" and "Atypical antipsychotics", "Novel antipsychotics", "New antipsychotics", "Quetiapine", "Olanzapine", "Aripiprazole", "Risperidone", "Paliperidone", "Clozapine", "Asenapine", "Iloperidone", "Amisulpiride", "Ziprasidone", "Zotepine", "Sertindole", "Lurasidone" or "Perospirone". RESULTS: Twelve randomized controlled trials (RCTs) and 22 open trials were considered. Despite an overall lack of large-scale RCTs, there is some evidence supporting the efficacy of olanzapine and quetiapine in placebo controlled trials. In a recent and large RCT in elderly patients, risperidone and/or haloperidol were associated with a significantly worse outcome than placebo. While preliminary, the current comparative studies suggest that haloperidol and the AAPs olanzapine, quetiapine and risperidone are similarly effective, although treatment with AAPs is associated with a reduced incidence of extrapyramidal symptoms. Ziprasidone was not shown to be effective. No RCTs are available for other AAPs. CONCLUSIONS: Although the current evidence of the efficacy and tolerability of AAPs in the treatment of delirium is limited and the heterogeneity of the data precluded a meta-analysis, olanzapine and quetiapine seem to be adequate alternatives to haloperidol, especially in patients who are vulnerable for extrapyramidal symptoms, who require sedation or who have a history of haloperidol intolerance. Evidently, larger-scale RCTs are urgently required.

Associations between testosterone and metabolic syndrome in depressed and non-depressed older men and women.

OBJECTIVES: Older age and major depressive disorder (MDD) are both risk factors for the development of cardiovascular diseases. Testosterone has been associated with MDD and metabolic syndrome (MetS) in men, although associations in women are less clear. Therefore, we investigated whether testosterone is associated with MetS and whether this association is different for depressed and non-depressed older men and women. METHODS: In this prospective cohort study, 478 participants (349 patients with MDD and 129 controls) aged between 60 and 93 years from the Netherlands Study of Depression in Older Persons were included. Total testosterone (TT) and sex-hormone binding globulin levels were measured using a second-generation radioimmune assay. Free testosterone (FT) was calculated based on TT. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: A higher risk for MetS was found in men with low FT and TT (odds ratio [OR]: 0.67, 95% confidence interval [95%CI]: 0.47-0.95 and OR: 0.51, 95%CI: 0.34-0.75), and in women with high FT (OR: 1.41, 95%CI: 1.08-1.82). Strong associations in the same direction were found with adiposity, glucose, and plasma lipid MetS components at baseline, but not with changes in these components at 2-year follow-up. The associations did not significantly differ between MDD patients and controls. CONCLUSIONS: Independently of having MDD, low testosterone levels in men and, in contrast, high testosterone levels in women were significantly associated with MetS and its components.

Performance of the Psychotic Depression Assessment Scale as a Predictor of ECT Outcome.

OBJECTIVES: The presence of psychotic symptoms is an important predictor of responsiveness to electroconvulsive therapy (ECT). This study investigates whether a continuous severity measure, the Psychotic Depression Assessment Scale (PDAS), is a more accurate predictor. METHODS: Depression severity was assessed before and after the ECT course using the Montgomery-Asberg Depression Rating Scale (MADRS) in 31 patients with psychotic depression and 34 depressed patients without psychotic symptoms. Logistic regression models for MADRS response and remission were fitted, with either the PDAS total score or the dichotomous predictors "absence/presence of psychotic symptoms" as the independent variables. Age, episode duration, and treatment resistance were added as covariates. RESULTS: Both the asserted presence of psychotic symptoms and a higher PDAS total score reflected MADRS response (areas under the curve, 0.83 and 0.85, respectively), with MADRS remission also being predicted by the presence of psychotic symptoms and higher PDAS scores (areas under the curves, 0.86 and 0.84, respectively). Age was a contributor to these prediction models, with response and remission rates being highest in the older patients. Psychotic Depression Assessment Scale scores decreased significantly during ECT: at end point, 81.5% of the patients showed significant response and 63.9% had achieved remission. CONCLUSIONS: The PDAS indeed accurately predicts response to and remission after ECT in (psychotic) depression and most pronouncedly so in older patients but seems to have no clear advantage over simply verifying the presence of psychotic symptoms. This could be the consequence of a ceiling effect, as ECT was extremely effective in patients with psychotic depression.ClinicalTrials.gov: Identifier: NCT02562846.

Differences in Speed of Response of Depressive Symptom Dimensions in Older Persons During Electroconvulsive Therapy.

INTRODUCTION: Electroconvulsive therapy (ECT) is an important and effective treatment for depression. However, research on course trajectories of depressive symptoms during ECT is limited. Insight into putative differences in speed of response of depressive symptom dimensions may enable clinicians to optimally inform patients and their relatives. Therefore, we aim to examine course trajectories of depressive symptom dimensions in depressed older persons during ECT. METHODS: Data were derived from the Mood Disorders in Elderly treated with Electro Convulsive Therapy study, including 110 persons, aged 55 years or more, with a current diagnosis of major depressive disorder and referred for ECT. Exploratory factor analysis was used to identify symptom dimensions, using the 10 depression items of the Montgomery-Åsberg Depression Rating Scale (MADRS). Differences in course trajectories of symptom dimension during 2 weeks were examined by multilevel analyses. RESULTS: Three symptom dimensions were identified: a "mood," "melancholic," and "suicidal" dimension. Mood showed a significantly greater severity decline as compared with melancholic and suicidal at the 1-week follow-up. At the 2-week follow-up, both mood and melancholic demonstrated a significantly greater decline as compared with suicidal. However, because scores on the suicidality item of the Montgomery-Asberg Depression Rating Scale were already lower at baseline compared with the other items, a floor effect cannot be ruled out. DISCUSSION: All symptom dimensions of depression showed a rapid response to ECT. Our findings did not support the general assumption that suicidal symptoms may be the first to improve. However, a floor effect on the suicidality item cannot be ruled out.

Subjective insomnia symptoms and sleep duration are not related to hypothalamic-pituitary-adrenal axis activity in older adults.

Insomnia symptoms are highly prevalent in depressed older adults. This study investigates the association between hypothalamic-pituitary-adrenal (HPA) axis activity and symptoms of insomnia, respectively, sleep duration among 294 depressed and 123 non-depressed older adults of the Netherlands Study of Depression in Older people (NESDO) study. Insomnia symptoms were defined as clinically relevant when having a score ≥ 10 points on the Women's Health Initiative Insomnia Rating Scale (WHIIRS). Sleep duration was categorized in short (≤ 6 h per night), normal (7-8 h per night) and long (≥ 9 h per night) duration. Salivary cortisol levels were used to assess the following cortisol parameters for HPA axis activity: area under the curve with respect to the increase (AUCi) and to the ground (AUCg), diurnal slope, evening cortisol level and dexamethasone suppression ratio. Clinically relevant insomnia symptoms were present in 46% of the participants. Thirty-two per cent of the participants were short sleepers, whereas 16% were long sleepers. However, univariate analyses showed no differences in any of the HPA axis parameters between people with and without insomnia symptoms or between the three groups with different sleep duration. In addition, no significant interaction was found between a diagnosis of depression or the severity of depressive symptoms and any of the cortisol parameters in relation to insomnia symptoms or sleep duration.

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

OBJECTIVES: To examine the six-year prognosis of patients with late-life depression and to identify prognostic factors of an unfavorable course. DESIGN AND SETTING: The Netherlands Study of Depression in Older Persons (NESDO) is a multisite naturalistic prospective cohort study with six-year follow-up. PARTICIPANTS: Three hundred seventy-eight clinically depressed patients (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision criteria) and 132 nondepressed comparisons were included at baseline between 2007 and 2010. MEASUREMENTS: Depression was measured by the Inventory of Depressive Symptomatology at 6-month intervals and a diagnostic interview at 2- and 6-year follow-up. Multinomial regression and mixed model analyses were both used to identify depression-related clinical, health, and psychosocial prognostic factors of an unfavorable course. RESULTS: Among depressed patients at baseline, 46.8% were lost to follow-up; 15.9% had an unfavorable course, i.e., chronic or recurrent; 24.6% had partial remission; and 12.7% had full remission at six-year follow-up. The relative risk of mortality in depressed patients was 2.5 (95% confidence interval 1.26-4.81) versus nondepressed comparisons. An unfavorable course of depression was associated with a younger age at depression onset; higher symptom severity of depression, pain, and neuroticism; and loneliness at baseline. Additionally, partial remission was associated with chronic diseases and loneliness at baseline when compared with full remission. CONCLUSIONS: The long-term prognosis of late-life depression is poor with regard to mortality and course of depression. Chronic diseases, loneliness, and pain may be used as putative targets for optimizing prevention and treatment strategies for relapse and chronicity.

Lifestyle factors and the course of depression in older adults: A NESDO study.

OBJECTIVES: To investigate whether lifestyle indicators including physical exercise, sleep duration, alcohol use, body mass index, smoking status, and a composite lifestyle index are associated with the depression course in older adults. METHODS: Data of 283 older adults were used from the Netherlands Study of Depression in Older Persons. Depressive disorders at baseline were assessed with the Composite International Diagnostic Interview. The depression course at 2-year follow-up was assessed with the Inventory of Depressive Symptoms (IDS, score 0-84) every 6 months; physical exercise with the International Physical Activity Questionnaire; alcohol use with the Alcohol Use Disorders Identification Test; body mass index by anthropometry; and sleep duration and smoking status by interview questions. A composite lifestyle index was calculated by summing scores assigned to each lifestyle factor, with a higher score indicating healthier behavior. RESULTS: Of all participants, 61.1% had chronic depression (all IDS scores 14-84), 20.1% had intermittent depression (1 IDS score ≤ 14), and 18.7% remitted depression (last 2 IDS scores ≤14). None of the investigated lifestyle indicators, nor the composite lifestyle index was associated with depression course, after adjustment for covariates. CONCLUSIONS: Lifestyle factors do not predict the course of depression at 2-year follow-up in older adults.

Correlates of sleep disturbances in depressed older persons: the Netherlands study of depression in older persons (NESDO).

OBJECTIVES: Sleep disturbances are common among depressed older persons. To gain insight into sleep disturbances in late-life depression, their occurrence and correlates were assessed. METHODS: Baseline data of 294 depressed older persons of the Netherlands Study of Depression in Older persons study were used. A diagnosis of current depression according to the diagnostic and statistical manual of mental disorders-IV (DSM-IV) was assessed with the Composite International Diagnostic Interview. Sleep disturbances were measured with the five-item Women's Health Initiative Insomnia Rating Scale, and considered present with a score of ≥10 points. RESULTS: Sleep disturbances were present in 59.9% of the depressed older persons. Bivariate linear regression analyses showed that presence of sleep disturbances was associated with fewer years of education, use of alcohol, the number of chronic diseases, higher pain intensity scores, use of more benzodiazepines, more anxiety and severity of depressive symptoms. In multivariate analyses, severity of depression appeared to be the only independent correlate. CONCLUSIONS: Sleep disturbances are highly prevalent in patients with late-life depression and independently correlated with the severity of depression. Treatment of depression may result in improvement of sleep disturbances, although cognitive behavioral interventions that focus on both depression and sleep disturbances may also be effective.

Clinical validation of the Psychotic Depression Assessment Scale (PDAS) against independent global severity ratings in older adults.

OBJECTIVES: According to a recent study, ratings on the Psychotic Depression Assessment Scale (PDAS) obtained via a dedicated semi-structured interview are valid measures of the severity of psychotic depression. This study aimed to further test the validity, scalability and responsiveness of the PDAS in older adults using independent ratings on the Clinical Global Impression Scale - Severity (CGI-S) and the Montgomery-Asberg Depression Rating Scale (MADRS) as references. METHODS: Ratings were performed at admission and discharge at two old age psychiatric wards in Flanders, Belgium. In total, 62 older adults (mean age: 74.3 years) with psychotic depression were included. The PDAS was rated by trained nurses using the semi-structured PDAS interview. Senior psychiatrists scored the participants on the CGI-S. Psychologists or experienced nurses rated participants on the MADRS. Clinical validity was assessed by correlating the PDAS total scores with CGI-S ratings and MADRS total scores. Mokken analysis was performed to assess the scalability of the PDAS. Responsiveness was assessed by comparing the proportion of participants in remission (PDAS total score <8 at study baseline and endpoint). RESULTS: The Spearman correlation coefficients were 0.76 and 0.79 for the PDAS versus CGI-S and PDAS versus MADRS, respectively. The Mokken analysis yielded a Loevinger coefficient of 0.46, which is indicative of scalability. At admission, no participants met the PDAS remission criterion. At discharge, 54% (95% confidence interval: 47%-60%) of the patients met this criterion. CONCLUSION: The PDAS appears to be a clinically valid, scalable and responsive measure of the severity of psychotic depression in older adults.

Risk Factors for Depression: Differential Across Age?

INTRODUCTION: The occurrence of well-established risk factors for depression differs across the lifespan. Risk factors may be more strongly associated with depression at ages when occurrence, and therefore expectance, is relatively low ("on-time off-time" hypothesis). This large-scale study examined absolute and relative risks of established risk factors for depression across the lifespan. METHODS: Participants were 2,215 currently or never depressed adults aged 18 to 93 years from two cohort studies: NESDA and NESDO. The occurrence of 19 established risk factors (absolute risk) was examined in different age groups. In addition, the relative risk of these risk factors for depression was compared across age groups by examining risk factor × age interaction. RESULTS: The occurrence of all risk factors differed significantly across age groups. Although most risk factors had significant associations with depression across the lifespan, for five risk factors the strength of the association was age-dependent. Stronger associations with depression in younger age were found for childhood abuse, pain, higher body mass index (BMI) and number of chronic diseases, whereas low income imposed a stronger risk in older age. Associations with depression were strongest in age groups where occurrence was lowest. CONCLUSIONS: Although the exposure to risk factors changes across the lifespan, the relative risk associating them to depression remains similar for most risk factors. Some specific risk factors (low income, and health factors pain, BMI, and number of chronic diseases), however, seem more strongly associated with depression in ages in which occurrence is lowest and least expected.

Plasma Testosterone and the Course of Major Depressive Disorder in Older Men and Women.

OBJECTIVE: To investigate associations between testosterone levels and major depressive disorder (MDD) in older men and women. METHODS: In a cross-sectional, 2-year prospective analyses within the Netherlands Study on Depression in Older persons cohort study, 469 participants comprised 350 patients with MDD and 119 nondepressed participants in the comparison group (mean age 70.5 ± 7.3 years; 166 [35.4%] men). MDD was assessed by the Composite International Diagnostic Interview. Baseline plasma total testosterone and sex hormone binding globulin (SHBG) were assessed to calculate free testosterone. The Inventory of Depressive Symptomatology was assessed every 6 months. RESULTS: Whereas SHBG levels did not differ between the depressed/nondepressed groups (F(1,149) = 0.075, p = 0.78), men with MDD had lower mean total and free testosterone levels than the comparison group in the multivariate adjusted analyses (F(1,150) = 7.249, p = 0.008, Cohen's d = 0.51; and F(1,149) = 8.548, p = 0.004 Cohen's d = 0.55, respectively). This could be ascribed to lower testosterone in men with "pure" MDD and not in men with MDD and comorbid anxiety. Nine men (5.4%) had a total testosterone level < 8 nmol/L, of whom 8 suffered from MDD. In women, hormone levels showed no significant difference between the groups. In men (using all five measurement points during follow-up) baseline free testosterone was inversely associated with depression severity in the adjusted analyses (ß = -0.15, t(151) = -2.15, p = 0.03). CONCLUSION: Testosterone levels were lower in men with MDD compared with healthy men after adjustment for confounders, such as body mass index. No significant associations were found in women.

Effect of chronic somatic diseases on the course of late-life depression.

OBJECTIVE: To examine the influence of specific chronic somatic diseases and overall somatic diseases burden on the course of depression in older persons. METHODS: This was a prospective cohort study with a 2-year follow-up. Participants were depressed persons (n = 285) from the Netherlands Study of Depression in Older Persons. The presence of chronic somatic diseases was based on self-report. Diagnosis of depression was assessed with the Composite International Diagnostic Interview, and severity of depression was measured with the Inventory of Depressive Symptomatology Self-report. RESULTS: Cardiovascular diseases (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.02-2.72, p = 0.041), musculoskeletal diseases (OR = 1.71, 95% CI = 1.04-2.80, p = 0.034), and the number of chronic somatic diseases (OR = 1.37, 95% CI = 1.16-1.63, p < 0.001) were associated with having a depressive disorder at 2-year follow-up. Furthermore, chronic non-specific lung diseases, cardiovascular diseases, musculoskeletal diseases, cancer, or cumulative somatic disease burden were associated with a chronic course of depression. CONCLUSIONS: Somatic disease burden is associated with a poor course of late-life depression. The course of late-life depression is particularly unfavorable in the presence of chronic non-specific lung diseases, cardiovascular diseases, musculoskeletal diseases, and cancer. Copyright © 2016 John Wiley & Sons, Ltd.

Validity of the three apathy items of the Geriatric Depression Scale (GDS-3A) in measuring apathy in older persons.

OBJECTIVE: The Geriatric Depression Scale (GDS)-3A, a three-item subset of the GDS-15, is increasingly used as a measure for apathy in research settings to assess factors associating with this neuropsychiatric syndrome. We aimed to assess how accurately the GDS-3A discriminates between presence and absence of apathy in two populations of community-dwelling older persons, using the Apathy Scale as reference standard. METHODS: Baseline data were used from 427 participants of the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study Leiden and 1118 participants of the PROactive Management Of Depression in the Elderly (PROMODE) Study, all ≥75 years and with available GDS-3A and Apathy Scale measurements. A cut-off score of ≥14 was used for presence of apathy according to the Apathy Scale. Areas under the receiver operating characteristic curve (AUC) were calculated. Based on the likelihood ratios for GDS-3A scores, a cut-off of ≥2 was used for presence of apathy according to the GDS-3A to calculate test characteristics. RESULTS: The AUC was 0.68 (95% confidence interval 0.62-0.73) in the DANTE Study and 0.72 (0.67-0.77) in the PROMODE Study. In the DANTE Study sensitivity was 29.3% (21.4-38.1) and specificity was 88.5% (84.4-91.8), whereas in the PROMODE Study sensitivity was 32.8% (24.5-41.1) and specificity 92.6% (90.9-94.2). Stratification on population characteristics did not yield more favourable test characteristics. CONCLUSION: The GDS-3A has low sensitivity and high specificity as a measure of apathy in two populations of older persons. Using the GDS-3A in research might yield estimates biassed towards the null in case of non-differential misclassification. Copyright © 2016 John Wiley & Sons, Ltd.

Apathy in Older Persons With Depression: Course and Predictors: The NESDO Study.

OBJECTIVES: Apathy is a common behavioral syndrome, influencing different areas of daily functioning and often seen in depression. Little is known about the course of apathy in depression. In this study, we examine the course and predicting factors of apathy in older persons with depression. METHOD: Data of 266 older persons with depression participating in the Netherlands Study of Depression in Older Persons, all aged at least 60 years with complete Apathy Scale scores at baseline and 2-year follow-up, were included in this study. Associations between several baseline variables and severity, incidence, and persistence of apathy were examined using regression analyses. RESULTS: At 2-year follow-up, the severity of apathy was predicted by the severity of apathy at baseline, and incidence rate of apathy was 36%, with a lower baseline Mini-Mental State Examination score being an independent predictor. Older persons with incident apathy did not differ in remission rate of depression compared to those without apathy at follow-up. Persistence rate of apathy was 80% and was independently predicted by a higher baseline Apathy Scale score and, surprisingly, by less use of benzodiazepines. Persons with persistent apathy were less likely to recover from depression than those who remitted from apathy. CONCLUSION: Severity of apathy at baseline, but not depression, predicted apathy at follow-up. Incident apathy was predicted by poorer cognitive function, whereas severe apathy at baseline predicted its persistence. Remarkably, new apathy was not associated with worse outcome of depression whereas persistent apathy was.

Latent class analysis of the Apathy Scale does not identify subtypes of apathy in general population-based older persons.

OBJECTIVES: To identify clinically relevant subtypes of apathy in older persons using latent class analysis (LCA) and investigate the distribution of different characteristics across these subtypes. MEASUREMENTS: Cross-sectional data of 122 older persons (mean age 84 years, 60% female) participating in the general population-based PROactive Management Of Depression in the Elderly study, with apathy according to a score of 14 or higher on the Apathy Scale, were included for LCA. All 14 items of the Apathy Scale were used as indicator variables. Several characteristics were examined including sociodemographics, depressive, and anxiety symptoms; global cognitive function; quality of life indicators; hazardous alcohol intake (drinking ≥ 14 consumptions per week); and perceived chronic pain. RESULTS: Three distinct LCA classes were found classifying 17%, 7%, and 76% of the participants respectively. Individuals in the first class had a higher level of education and were less likely to live alone. Those in the second class had higher apathy and depression scores, lived more frequently alone and used more alcohol. Individuals in the third class showed a lower level of education and worse cognitive function. In multivariable multinomial analyses, only a lower educational level and higher scores on the Apathy Scale were significant predictors for class membership. CONCLUSION: Differences between LCA-derived classes were minimal, suggesting that in a general population-based cohort the Apathy Scale measures a homogeneous construct. Copyright © 2016 John Wiley & Sons, Ltd.