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.

Distinct functional subnetworks of cognitive domains in older adults with minor cognitive deficits.

Although past research has established a relationship between functional connectivity and cognitive function, less is known about which cognitive domains are associated with which specific functional networks. This study investigated associations between functional connectivity and global cognitive function and performance in the domains of memory, executive function and psychomotor speed in 166 older adults aged 75-91 years (mean = 80.3 ± 3.8) with minor cognitive deficits (Mini-Mental State Examination scores between 21 and 27). Functional connectivity was assessed within 10 standard large-scale resting-state networks and on a finer spatial resolution between 300 nodes in a functional connectivity matrix. No domain-specific associations with mean functional connectivity within large-scale resting-state networks were found. Node-level analysis revealed that associations between functional connectivity and cognitive performance differed across cognitive functions in strength, location and direction. Specific subnetworks of functional connections were found for each cognitive domain in which higher connectivity between some nodes but lower connectivity between other nodes were related to better cognitive performance. Our findings add to a growing body of literature showing differential sensitivity of functional connections to specific cognitive functions and may be a valuable resource for hypothesis generation of future studies aiming to investigate specific cognitive dysfunction with resting-state functional connectivity in people with beginning cognitive deficits.

Functional connectivity in older adults-the effect of cerebral small vessel disease.

Ageing is associated with functional reorganization that is mainly characterized by declining functional connectivity due to general neurodegeneration and increasing incidence of disease. Functional connectivity has been studied across the lifespan; however, there is a paucity of research within the older groups (≥75 years) where neurodegeneration and disease prevalence are at its highest. In this cross-sectional study, we investigated associations between age and functional connectivity and the influence of cerebral small vessel disease (CSVD)-a common age-related morbidity-in 167 community-dwelling older adults aged 75-91 years (mean = 80.3 ± 3.8). Resting-state functional MRI was used to determine functional connectivity within ten standard networks and calculate the whole-brain graph theoretical measures global efficiency and clustering coefficient. CSVD features included white matter hyperintensities, lacunar infarcts, cerebral microbleeds, and atrophy that were assessed in each individual and a composite score was calculated. Both main and interaction effects (age*CSVD features) on functional connectivity were studied. We found stable levels of functional connectivity across the age range. CSVD was not associated with functional connectivity measures. To conclude, our data show that the functional architecture of the brain is relatively unchanged after 75 years of age and not differentially affected by individual levels of vascular pathology.

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.

Cognitive performance among older adults with psychotic depression compared to non-psychotic depression.

It remains unclear whether psychotic depression (PD) compared to non-psychotic depression (non-PD) among older adults is associated with poorer cognitive performance. For inpatients (60+) with a major depressive episode, cognitive performance in PD and non-PD (categorical) were compared as well as the relationship between symptom severity for depression and psychosis (dimensional) and cognition. Of 90 participants (on average 72.7 years old; range 60-92), 64% were female. The severity of depressive- and psychotic symptoms are both negatively associated with cognitive functioning among older adults with depression. This is of relevance for the treatment of this vulnerable group of patients.

Telephone follow-up to reduce unplanned hospital returns for older emergency department patients: A randomized trial.

BACKGROUND/OBJECTIVES: Telephone follow-up calls could optimize the transition from the emergency department (ED) to home for older patients. However, the effects on hospital return rates are not clear. We investigated whether telephone follow-up reduces unplanned hospitalizations and/or unplanned ED return visits within 30 days of ED discharge. DESIGN: Pragmatic randomized controlled trial with allocation by month; odd months intervention group, even months control group. SETTING: Two ED locations of a non-academic teaching hospital in The Netherlands. PARTICIPANTS: Community-dwelling adults aged ≥70 years, discharged home from the ED were randomized to the intervention group (N = 4732) or control group (N = 5104). INTERVENTION: Intervention group patients: semi-scripted telephone call from an ED nurse within 24 h after discharge to identify post-discharge problems and review discharge instructions. Control group patients: scripted satisfaction survey telephone call. MEASUREMENTS: Primary outcome: total number of unplanned hospitalizations and/or ED return visits within 30 days of ED discharge. SECONDARY OUTCOMES: separate numbers of unplanned hospitalizations and ED return visits. Subgroup analysis by age, sex, living condition, and degree of crowding in the ED at discharge. RESULTS: Overall, 42% were males, and median age was 78 years. In the intervention group, 1516 of 4732 patients (32%) consented, and in the control group 1659 of 5104 (33%) patients. Unplanned 30-day hospitalization and/or ED return visit was found in 16% of intervention group patients and 14% of control group patients (odds ratio 1.16; 95% confidence interval: 0.96-1.42). Also, no statistically significant differences were found in secondary outcome measures. Within the subgroups, the intervention did not have beneficial effects for the intervention group. CONCLUSION: Telephone follow-up after ED discharge in older patients did not result in reduction of unplanned hospital admissions and/or ED return visits within 30 days. These results raise the question of whether other outcomes could be improved by post-discharge ED telephone follow-up.

The effect of a telephone follow-up call for older patients, discharged home from the emergency department on health-related outcomes: a systematic review of controlled studies.

BACKGROUND: Older patients discharged from the emergency department (ED) are at increased risk for adverse outcomes. Transitional care programs offer close surveillance after discharge, but are costly. Telephone follow-up (TFU) may be a low-cost and feasible alternative for transitional care programs, but its effects on health-related outcomes are not clear. AIM: We systematically reviewed the literature to evaluate the effects of TFU by health care professionals after ED discharge to an unassisted living environment on health-related outcomes in older patients compared to controls. METHODS: We conducted a multiple electronic database search up until December 2019 for controlled studies examining the effects of TFU by health care professionals for patients aged ≥65 years, discharged to an unassisted living environment from a hospital ED. Two reviewers independently assessed eligibility and risk of bias. RESULTS: Of the 748 citations, two randomized controlled trials (including a total of 2120 patients) met review selection criteria. In both studies, intervention group patients received a scripted telephone intervention from a trained nurse and control patients received a patient satisfaction survey telephone call or usual care. No demonstrable benefits of TFU were found on ED return visits, hospitalization, acquisition of prescribed medication, and compliance with follow-up appointments. However, many eligible patients were not included, because they were not reached or refused to participate. CONCLUSIONS: No benefits of a scripted TFU call from a nurse were found on health services utilization and discharge plan adherence by older patients after ED discharge. As the number of high-quality studies was limited, more research is needed to determine the effect and feasibility of TFU in different older populations. PROSPERO registration number CRD42019141403.

[Fitness to drive when taking medicines]. / Rijvaardigheid bij het gebruik van geneesmiddelen.

The regulations for driving fitness of people using drugs with potential influence on driving capability are embodied in the 'Regelingeisengeschiktheid 2000' (REG2000). The Health Council of the Netherlands (HCN) adviced to design more strict regulations for professional drivers. This advice has not yet been approved by the minister due to implementation complexity. The HCN recommends to follow the by the KNMP formulated advices when using category II psychostimulants or category III antidepressants, benzodiazepines, antipsychotics, antihistamines, anti-epileptics or opioids. The KNMP advices for driving participation are broadly available via the public websites www.apotheek.nl and www.rijveiligmetmedicijnen.nl. Both websites are written in accessible language level. The HCN advices to enhance scientific research concerning influence on driving fitness before approving a drug, to use standard procedures to prevent ad hoc decisions concerning driving fitness and the use of checklists for doctors when preparing driving fitness attests.

Lower Blood Pressure, Small-Vessel Disease, and Apathy in Older Persons With Mild Cognitive Deficits.

BACKGROUND: In older persons, both high and low blood pressure (BP) levels are associated with symptoms of apathy. Population characteristics, such as burden of cerebral small-vessel disease (CSVD), may underlie these apparently contradictory findings. We aimed to explore, in older persons, whether the burden of CSVD affects the association between BP and apathy. DESIGN: Cross-sectional study. SETTING: Primary care setting, the Netherlands. PARTICIPANTS: Community-dwelling older persons (mean age = 80.7 years; SD = 4.1 years) with mild cognitive deficits and using antihypertensive treatment, participating in the baseline measurement of the magnetic resonance imaging substudy (n = 210) of the Discontinuation of Antihypertensive Treatment in the Elderly Study Leiden. MEASUREMENTS: During home visits, BP was measured in a standardized way and apathy was assessed with the Apathy Scale (range = 0-42). Stratified linear regression analyses were performed according to the burden of CSVD. A higher burden of CSVD was defined as 2 or more points on a compound CSVD score (range = 0-3 points), defined as presence of white matter hyperintensities (greater than median), any lacunar infarct, and/or two or more microbleeds. RESULTS: In the entire population, those with a lower systolic and those with a lower diastolic BP had more symptoms of apathy (ß = -.35 [P = .01] and ß = -.66 [P = .02], respectively). In older persons with a higher burden of CSVD (n = 50 [24%]), both lower systolic BP (ß = -.64, P = .02) and lower diastolic BP (ß = -1.6, P = .01) were associated with more symptoms of apathy, whereas no significant association was found between BP and symptoms of apathy in older persons with a lower burden of CSVD (n = 160). CONCLUSIONS: Particularly in older persons with a higher burden of CSVD, lower BP was associated with more symptoms of apathy. Adequate BP levels for optimal psychological functioning may vary across older populations with a different burden of CSVD. J Am Geriatr Soc 68:1811-1817, 2020.

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.

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.

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.

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.

The role of metabolic syndrome in late-life depression over 6 years: The NESDO study.

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.

Apathy Is Associated With Greater Decline in Subjective, but not in Objective Measures of Physical Functioning in Older People Without Dementia.

Background: In older people, both apathy and depression (which frequently co-occurs with apathy) have been associated with poor physical functioning, a major health concern. We investigated the association between apathy and physical functioning in older people without dementia and whether this association is modified by depression. Methods: We used the data from 380 older participants (with and without depression) taking part in the Netherlands Study of Depression in Older Persons, with baseline scores on the Apathy Scale and baseline and 2-year follow-up scores on at least one measure of physical functioning. These included the International Physical Activities Questionnaire (IPAQ, self-reported), WHO Disability Assessment Schedule (WHO-DASII mobility subset, self-reported), walking speed, or handgrip strength. Multivariable linear regression analyses were performed to examine the association between apathy at baseline and physical functioning at 2-year follow-up. We also investigated effect modification by sex, age, and depression. Results: Cross-sectionally, participants with higher baseline Apathy Scale scores performed significantly worse on all measures of physical functioning. Longitudinally, higher baseline Apathy Scale scores were associated with higher delta scores on the IPAQ (B = -59.81) in the basic model, and higher delta scores on the WHO-DASII (B = .09) in all models. Apathy was not associated with higher delta scores for walking speed or handgrip strength. Furthermore, sex, age, and depression did not modify any association. Conclusion: In a Dutch cohort of older people without dementia, apathy was associated with more decline in self-reported, but not in objective physical functioning. Sex, age, and depression did not modify these associations. In older people with apathy, subjective decline may precede decline in physical performance tests.

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.

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.

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.

The Six-Item Cognitive Impairment Test Is Associated with Adverse Outcomes in Acutely Hospitalized Older Patients: A Prospective Cohort Study.

AIM: The study aim was to investigate whether cognitive impairment, measured by the Six-Item Cognitive Impairment Test (6-CIT), is an independent predictor of adverse outcomes in acutely hospitalized older patients. METHODS: This was a prospective multicenter study including acutely hospitalized patients aged 70 years and older. Multivariable logistic regression was used to investigate whether impaired cognition (6-CIT ≥11 points) was an independent predictor of 90-day adverse outcome, a composite measure of functional decline and mortality. Secondary endpoints were hospital length of stay, new institutionalization, and in-hospital mortality. RESULTS: In total, 196 (15.6%) of 1,252 included patients had a 6-CIT ≥11. Median age was 80 years (interquartile range 74-85). Patients with impaired cognition had higher rates of 90-day adverse outcome (41.7% compared to 30.3% in 1,056 not cognitively impaired patients, p = 0.009). Impaired cognition was a predictor of 90-day adverse outcome with a crude odds ratio (OR) of 1.64 (95% CI 1.13-2.39), but statistical significance was lost when fully corrected for possible confounders (OR 1.44, 95% CI 0.98-2.11). For all secondary outcomes, impaired cognition was an independent predictor. CONCLUSIONS: In the acute hospital setting, the 6-CIT is associated with 90-day adverse outcome and is an independent predictor of hospital length of stay, new institutionalization, and in-hospital mortality.

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.